MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Seminars in Thrombosis and Hemostasis' source. Thu, 18 Mar 2010 14:31:56 +0100 http://www.medworm.com/index.php?rid=3285523&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245115 Semin Thromb Hemost 2009; 35: 820-826DOI: 10.1055/s-0029-1245115ABSTRACTData are limited on inhibitors in people with hemophilia (PWH) in developing countries. There is a perception that the overall prevalence of inhibitors, ranging from 7 to 19% in different reports, may be lower in these countries as compared with that reported from developed countries. This is possible given the fact that most patients are treated after 2 years of age with plasma-derived clotting factor concentrates. Whether genetic or other environmental factors also contribute to this needs further evaluation. There is a need to develop laboratory infrastructure and establish quality control programs for laboratory tests for inhibitors in developing countries. Management options vary widely given the socioeconomic div... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285523 Fri, 19 Feb 2010 14:31:24 +0100 3285523 http://www.medworm.com/index.php?rid=3285522&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245114 Semin Thromb Hemost 2009; 35: 814-819DOI: 10.1055/s-0029-1245114ABSTRACTThe development of inhibitors against therapeutically administered factors VIII or IX is actually the most challenging complication of hemophilia patients with inhibitors. The introduction of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII [rFVIIa]) has dramatically improved the management of bleeding episodes in such patients. Over the last decade, there have been increasing reports on the ability of bypassing agents to prevent surgical, joint, or other bleeds in inhibitor patients. The published data on the use of rFVIIa as a prophylactic treatment in hemophilia patients with inhibitors are reviewed in this article.[...]© Thieme Medical PublishersGet connected:... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285522 Fri, 19 Feb 2010 14:31:24 +0100 3285522 http://www.medworm.com/index.php?rid=3285521&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245113 Semin Thromb Hemost 2009; 35: 806-813DOI: 10.1055/s-0029-1245113ABSTRACTThe mainstay of therapy in patients with congenital hemophilia is factor replacement. However, the development of inhibitors in these patients is a major complication that represents an important challenge in hemophilia care. Development of inhibitors complicates the clinical course of severe hemophilia in up to 30% of patients with hemophilia A and up to 5% of patients with hemophilia B. Although the main short-term objective of the treatment of alloantibodies against factors VIIII and IX is to control the bleeding diathesis, the eradication of the inhibitor is the leading long-term goal. The management of severe bleeding episodes and the definitive eradication of the autoantibody are also the two main options of the ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285521 Fri, 19 Feb 2010 14:31:24 +0100 3285521 http://www.medworm.com/index.php?rid=3285520&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245112 This article reviews each of these elements, largely from the perspective of cross-laboratory studies undertaken within the framework of external quality assurance (EQA), a peer-laboratory process that aims to assess the ongoing performance of groups of similar laboratories. This review details the experience of the Royal College of Pathologists of Australasia Haematology Quality Assurance Program, and it also reflects on the experience of other EQA organizations. Our analysis reveals a wide variety of test practice among inhibitor testing laboratories, a wide variation in detected inhibitor levels in cross-tested samples, and substantial evidence of false-positive and false-negative detection of factor inhibitors. These findings hold some significance for the clinical management of patien... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285520 Fri, 19 Feb 2010 14:31:24 +0100 3285520 http://www.medworm.com/index.php?rid=3285519&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245111 This study includes the results of six different surveys for the period 2006 to 2008 with 100 to 170 participating laboratories. The overall between-laboratory variation ranged from 28% to 52% with a slightly lower variation for the Nijmegen assay (~39%) on average than for the Bethesda assay (~45%). The use of buffered normal pooled plasma as FVIII source showed better performance compared with the use of nonbuffered pooled plasma; likewise the use of FVIII-deficient plasma compared with the use of imidazole buffer. However, the combination of both was essential for lowest between-laboratory variation. The Nijmegen assay also showed better performance with respect to specificity and sensitivity than the Bethesda assay, although the results for neither were entirely satisfactory. In genera... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285519 Fri, 19 Feb 2010 14:31:24 +0100 3285519 http://www.medworm.com/index.php?rid=3285518&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245110 We report the results of external quality assessment exercises in which 60 to 120 centers performed factor VIII (FVIII) inhibitor testing on a series of samples over a 13-year period. Samples from seven different subjects were distributed for analysis comprising the following: four different subjects with severe hemophilia A with antibodies following replacement therapy, one subject with acquired hemophilia A and antibodies to FVIII, one subject with normal FVIII and an easily detected lupus anticoagulant, and one subject with mild hemophilia A and a difficult-to-detect lupus anticoagulant but without antibodies to FVIII. In all of the surveys the results obtained in different centers analyzing the same sample varied to an extent that would influence patient management decisions. In the UK... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285518 Fri, 19 Feb 2010 14:31:24 +0100 3285518 http://www.medworm.com/index.php?rid=3285517&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245109 This report summarizes the experience related to AH from a large Australian hemophilia center based in South Australia. We identified 25 patients retrospectively over 12 years (1997 to 2008) and reviewed diagnostic features, treatment for bleeds and to eradicate the autoantibody, treatment response, and survival outcomes. The incidence in South Australia was 1.20 cases per million/year with a median age of 78 years with an approximately equivalent sex ratio (12 males versus 13 females); median FVIII and inhibitor titer were 2.5 IU/dL and 11.0 BU/mL, respectively. Twenty-four patients were evaluated further. Thirteen patients (54%) required hemostatic agents, and rFVIIa was used in seven for major bleeds, of which four were limb or life threatening. Eighteen patients were treated by hematol... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285517 Fri, 19 Feb 2010 14:31:24 +0100 3285517 http://www.medworm.com/index.php?rid=3285516&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245108 Semin Thromb Hemost 2009; 35: 760-768DOI: 10.1055/s-0029-1245108ABSTRACTCoagulation factor inhibitors are antibodies that bind and neutralize specific procoagulant plasma proteins. The identification of coagulation factor inhibitors by the hemostasis laboratory requires a careful and systematic approach that excludes other possible causes of prolonged screening tests such as the activated partial thromboplastin time and prothrombin time. Once the laboratory is confident that a specific coagulation factor inhibitor is present in a sample, its strength or titer must be measured. The clinician will use this information as a treatment guide. The most frequently occurring factor inhibitors encountered in the hemostasis laboratory are those directed against factor VIII (FVIII), which can arise i... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285516 Fri, 19 Feb 2010 14:31:24 +0100 3285516 http://www.medworm.com/index.php?rid=3285515&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245107 This report describes in detail the various problems encountered with the assays used in the quantification of functional FVIII inhibitors.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285515 Fri, 19 Feb 2010 14:31:24 +0100 3285515 http://www.medworm.com/index.php?rid=3285514&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245106 Semin Thromb Hemost 2009; 35: 735-751DOI: 10.1055/s-0029-1245106ABSTRACTDevelopment of inhibitory antibodies (inhibitors) to factor VIII (FVIII) is the most serious adverse event in replacement therapy of hemophilia A patients. The etiology and management of this condition remain major challenges for both researchers and clinicians. In the present review, we discuss recent advances in understanding the molecular mechanisms by which inhibitors inactivate FVIII and experimental approaches used for the mapping of inhibitor epitopes. We also present a comparative analysis of treatment of hemophilia A patients with inhibitors with currently available bypassing agents—activated prothrombin complex concentrate (FEIBA VH; Baxter Healthcare Corp., Westlake Village, CA) and recombinant activat... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285514 Fri, 19 Feb 2010 14:31:24 +0100 3285514 http://www.medworm.com/index.php?rid=3285513&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245105 Semin Thromb Hemost 2009; 35: 723-734DOI: 10.1055/s-0029-1245105ABSTRACTThe most important complication in the treatment of hemophilia A patients today is the development of inhibitory antibodies against infused factor VIII (FVIII). Inhibitor development is caused by a complex interplay between both genetic and environmental factors. The risk of developing inhibitors is greatest in previously untreated patients with severe hemophilia A. Several genetic factors, such as a positive family history of inhibitors, ethnicity, FVIII genotype, and certain polymorphisms in immune modulatory genes, are associated with the risk of inhibitor development. Treatment-related factors, such as intensive treatment with FVIII for bleeds or surgery, are associated with a higher inhibitor risk. However, regula... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285513 Fri, 19 Feb 2010 14:31:24 +0100 3285513 http://www.medworm.com/index.php?rid=3285512&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245104 Semin Thromb Hemost 2009; 35: 719-722DOI: 10.1055/s-0029-1245104© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285512 Fri, 19 Feb 2010 14:31:24 +0100 3285512 http://www.medworm.com/index.php?rid=3285511&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245103 Semin Thromb Hemost 2009; 35: 715-718DOI: 10.1055/s-0029-1245103© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285511 Fri, 19 Feb 2010 14:31:24 +0100 3285511 http://www.medworm.com/index.php?rid=3285510&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1245102 Semin Thromb Hemost 2009; 35: 713-714DOI: 10.1055/s-0029-1245102© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3285510 Fri, 19 Feb 2010 07:05:34 +0100 3285510 http://www.medworm.com/index.php?rid=3073162&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242724 Semin Thromb Hemost 2009; 35: 711-711DOI: 10.1055/s-0029-1242724© Thieme Medical PublishersGet connected:Table of contents  |  FREE: Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073162 Thu, 10 Dec 2009 14:19:01 +0100 3073162 http://www.medworm.com/index.php?rid=3073161&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242723 Semin Thromb Hemost 2009; 35: 695-710DOI: 10.1055/s-0029-1242723ABSTRACTThrombophilia can be broadly defined as an increased tendency toward hypercoagulability and venous thrombosis. There are several defined risk factors for thrombosis, and these are generally distinguished as either acquired or congenital, although sometimes this distinction is blurred because of interrelationships. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavage-resistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus an... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073161 Thu, 10 Dec 2009 14:19:01 +0100 3073161 http://www.medworm.com/index.php?rid=3073160&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242722 Semin Thromb Hemost 2009; 35: 683-694DOI: 10.1055/s-0029-1242722ABSTRACTInherited thrombophilia, defined as a genetically determined tendency to develop venous thromboembolism (VTE), contributes to the pathogenesis of ~40% of VTE episodes. About 50% of carriers of inherited thrombophilic traits develop VTE, but the impact of the different abnormalities is variable in terms of clinical penetrance. Some rare abnormalities (natural anticoagulant deficiencies, homozygous factor V Leiden, and combined defects) result in more severe thrombophilic phenotypes, characterized by early-onset events, more frequent recurrence, and positive family history, whereas the common polymorphisms (heterozygous factor V Leiden and prothrombin G20210A) are associated with lower VTE risk, often in association with... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073160 Thu, 10 Dec 2009 14:19:01 +0100 3073160 http://www.medworm.com/index.php?rid=3073159&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242721 Semin Thromb Hemost 2009; 35: 671-682DOI: 10.1055/s-0029-1242721ABSTRACTClinicians are well aware of family history as a risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The underlying genetic architecture of CAD/MI is extremely complex and still poorly understood. Overall, the genetic heritability of CAD/MI is estimated to be near 40 to 60%. This proportion includes mainly genes that regulate known risk factors (e.g., lipid metabolism) but also genes involved in as yet unknown metabolic pathways. In the last 2 years, the systematic application of genome-wide association studies in the setting of large collaborative consortia including thousands of patients and controls has led to the identification of several new loci associated with CAD/MI. Here we review cur... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073159 Thu, 10 Dec 2009 14:19:01 +0100 3073159 http://www.medworm.com/index.php?rid=3073158&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242720 Semin Thromb Hemost 2009; 35: 665-670DOI: 10.1055/s-0029-1242720ABSTRACTIt is well known that exposure to particulate air pollutants is associated with the development of adverse health effects. In particular, there is growing evidence of a close relationship between increased levels of environmental pollutants and cardiovascular disease. Particle exposure may trigger acute cardiac events as well as promote the chronic development of cardiovascular disorders. Several biological mechanisms have been suggested to explain the important effect of air pollution on cardiovascular morbidity and mortality, although the exact pathways are not fully understood. The literature data on the short-term and long-term cardiovascular effects of particulate air pollutants are discussed in this review from a... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073158 Thu, 10 Dec 2009 14:19:01 +0100 3073158 http://www.medworm.com/index.php?rid=3073157&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242719 Semin Thromb Hemost 2009; 35: 654-664DOI: 10.1055/s-0029-1242719ABSTRACTProstate cancer is the most prevalent malignancy in men and the third leading cause of cancer deaths worldwide. Disorders of hemostasis are commonplace in patients with prostate cancer and include disseminated intravascular coagulation, venous thromboembolism, acute coronary syndrome, and postsurgical bleeding. These hemostatic disorders contribute to the mortality and morbidity of prostate cancer. The leading mechanisms proposed to underlie prostate cancer-related coagulopathies are thought to be a hyperexpression of tissue factor, cancer procoagulant, and platelet-activating factor, which is then accompanied by release of large amounts of both prothrombotic and profibrinolytic substances into the bloodstream. Given t... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073157 Thu, 10 Dec 2009 14:19:01 +0100 3073157 http://www.medworm.com/index.php?rid=3073156&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242718 Semin Thromb Hemost 2009; 35: 644-653DOI: 10.1055/s-0029-1242718ABSTRACTThe relationship between hemostasis and malignancy is well recognized, with both elements interacting in a “vicious cycle” where cancers overexpress procoagulants and thrombin, which in turn promote both prothrombotic potential and tumor growth, invasion, and spread. Indeed, venous thromboembolism, particularly idiopathic venous thrombosis, occurs frequently as a paraneoplastic phenomenon, and in turn several components of primary and secondary hemostasis (namely platelets, tissue factor, and thrombin) play an important role in primary tumor growth and metastasization. Despite the many and various mechanisms involved in this multifaceted relationship, anticoagulants might represent an attractive anticancer ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073156 Thu, 10 Dec 2009 14:19:01 +0100 3073156 http://www.medworm.com/index.php?rid=3073155&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242717 Semin Thromb Hemost 2009; 35: 630-643DOI: 10.1055/s-0029-1242717ABSTRACTA series of case-control studies in the last decade have shown the role of inherited thrombophilia in the occurrence of adverse obstetric outcomes. In small series of cases, it has been proven that rare inherited causes of thrombophilia such as natural anticoagulant deficiencies can be associated with fetal losses. The confirmed presence of antiphospholipid antibodies in plasma, representing an acquired thrombophilic condition, is also an established cause of fetal losses, although other studies with a smaller sample size have found an association with other obstetric complications, namely preeclampsia, fetal growth restriction, and abruption placentae. Case-control studies have been performed regarding the potential a... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073155 Thu, 10 Dec 2009 14:19:01 +0100 3073155 http://www.medworm.com/index.php?rid=3073154&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242716 Semin Thromb Hemost 2009; 35: 621-629DOI: 10.1055/s-0029-1242716ABSTRACTSystemic lupus erythematosus (SLE) is a potentially fatal multiorgan inflammatory disease that primarily affects females. Due to the heterogeneity of clinical manifestations and lack of laboratory tests that are both specific and sensitive for the disease, diagnosis of SLE can often be difficult. Although the precise etiology remains to be fully elucidated, it is probable that various environmental, genetic, and hormonal factors contribute to the development of the disease. Patients with SLE have an increased risk for premature thrombosis and/or atherosclerosis, with up to half experiencing a thrombotic event. Furthermore, antiphospholipid antibodies probably play a key role in the development of thrombosis by affectin... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073154 Thu, 10 Dec 2009 14:19:01 +0100 3073154 http://www.medworm.com/index.php?rid=3073153&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242715 Semin Thromb Hemost 2009; 35: 613-620DOI: 10.1055/s-0029-1242715ABSTRACTPolycystic ovary syndrome (PCOS) is a common endocrine disorder associated with multiple comorbidities such as diabetes, dyslipidemia, hypertension, and metabolic syndrome, all of which predispose women with PCOS to early atherosclerosis. Women with PCOS also have a higher prevalence of subclinical atherosclerosis, as reflected in dysregulation of endothelial function, increased carotid intimal-medial thickness, and presence of coronary artery calcification. Preliminary data indicate that serum biomarkers of cardiovascular disease such as high-sensitivity C-reactive protein, homocysteine, and adiponectin are abnormal in women with PCOS. There is limited data on abnormalities in the coagulation and fibrinolytic systems,... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073153 Thu, 10 Dec 2009 14:19:01 +0100 3073153 http://www.medworm.com/index.php?rid=3073152&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242714 Semin Thromb Hemost 2009; 35: 605-612DOI: 10.1055/s-0029-1242714ABSTRACTThis review summarizes current knowledge of the effects of polycystic ovary syndrome, Cushing's syndrome, thyrotoxicosis, hypothyroidism, primary hyperparathyroidism, acromegaly, hypopituitarism, and growth hormone deficiency on coagulation and fibrinolysis. Several abnormalities of the coagulation-fibrinolytic system have been described among patients affected by these endocrine disorders. Although further larger studies are needed to provide more definitive information, clinically overt hypothyroidism appears to be associated with a bleeding tendency, whereas all other endocrine diseases appear to be associated with a thrombotic tendency. The disorders of coagulation and fibrinolysis observed in these endocrine patho... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073152 Thu, 10 Dec 2009 14:19:01 +0100 3073152 http://www.medworm.com/index.php?rid=3073151&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242713 Semin Thromb Hemost 2009; 35: 597-604DOI: 10.1055/s-0029-1242713ABSTRACTVenous thromboembolism (VTE) can be considered a multifactorial disorder involving a variety of inherited and acquired prothrombotic conditions and events. Although greater emphasis has classically been given to traditional thrombophilic risk factors, there is increasing recognition of less typical precipitating conditions and events. Indeed, the list of plausible but unusual triggers of thrombosis includes sneezing and coughing attacks, eating, migraine, sexual intercourse, strenuous physical exercise, drug abuse, and defecation. Although it is difficult to assert conclusively the true contribution of such events to the etiology of acute episodes of venous thrombosis, it seems reasonable to conclude that the concomita... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073151 Thu, 10 Dec 2009 14:19:01 +0100 3073151 http://www.medworm.com/index.php?rid=3073150&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242712 Semin Thromb Hemost 2009; 35: 591-595DOI: 10.1055/s-0029-1242712© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073150 Thu, 10 Dec 2009 14:19:01 +0100 3073150 http://www.medworm.com/index.php?rid=3073149&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1242711 Semin Thromb Hemost 2009; 35: 587-590DOI: 10.1055/s-0029-1242711© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=3073149 Thu, 10 Dec 2009 14:19:01 +0100 3073149 http://www.medworm.com/index.php?rid=2840353&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240018 Semin Thromb Hemost 2009; 35: 574-585DOI: 10.1055/s-0029-1240018ABSTRACTAtrial fibrillation (AF) requires anticoagulation for prevention of arterial embolism, especially in the presence of defined risk factors summarized in the CHADS score (congestive heart disease, hypertension, age >75 years, diabetes, history of ischemic stroke or transient cerebral ischemia). Vitamin K antagonists as drugs of choice have several limitations. International normalized ratio (INR) adjustment to 2.0 to 3.0 may be difficult to maintain, and doses vary widely between patients. Inherited variations of the vitamin K epoxide reductase C1 enzyme and of the cytochrome P450 2C9 system influence the dosage as well as exogenous factors such as food and drug intake or intercurrent diseases. Increasing age and risk... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840353 Tue, 29 Sep 2009 16:47:21 +0100 2840353 http://www.medworm.com/index.php?rid=2840352&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240017 Semin Thromb Hemost 2009; 35: 568-573DOI: 10.1055/s-0029-1240017ABSTRACTThe efficacy of adjusted-dose oral anticoagulant therapy (OAT) in the prevention of thrombotic complications in various clinical conditions is well documented. Management of OAT requires a trained physician, an organized system of follow-up, reliable international normalized ratio monitoring, and good patient communication and education. Drug interactions with coumarins are a major cause of excessive anticoagulation and hence could be an important determinant of bleeding in patients on OAT.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840352 Tue, 29 Sep 2009 16:47:21 +0100 2840352 http://www.medworm.com/index.php?rid=2840351&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240016 Semin Thromb Hemost 2009; 35: 560-567DOI: 10.1055/s-0029-1240016AbstractMost patients with atrial fibrillation need anticoagulant treatment with vitamin K antagonists for prevention of thromboembolism, in particular ischemic stroke. Many studies show the efficacy of this treatment but also that it is difficult to keep patients who use vitamin K antagonists in the proper treatment range. Both a too low and a too high intensity of anticoagulation significantly increase the risk of adverse events. Hence repeated monitoring of the intensity of anticoagulation and dose adjustments are required. Management strategies that improve the time in the therapeutic target range are computer-assisted dosing algorithms and centralized care in anticoagulation clinics. In addition, self-testing of the inter... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840351 Tue, 29 Sep 2009 16:47:21 +0100 2840351 http://www.medworm.com/index.php?rid=2840350&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1241048 We describe old and new paradigms of the use of oral anticoagulation. In the future, increased comprehensibility of stroke risk scores, development of a validated clinical bleed risk score, and new patient and physician user-friendly antithrombotic medication may contribute to improved adequate use of oral anticoagulation in AF patients.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840350 Tue, 29 Sep 2009 16:47:21 +0100 2840350 http://www.medworm.com/index.php?rid=2840349&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240015 Semin Thromb Hemost 2009; 35: 548-553DOI: 10.1055/s-0029-1240015ABSTRACTThe burden of atrial fibrillation (AF) worldwide is projected to increase substantially over the next few decades in part due to an aging population. AF increases the risk of stroke approximately fivefold. The population-attributable risk for stroke by age is considerable: 1.5% for those individuals 50 to 59 years of age compared with 23.5% for those ≥80 years of age. Vitamin K antagonists (VKAs) like warfarin have been shown to greatly reduce the risk of stroke. However, despite their proven efficacy, VKAs remain underused, particularly among elderly patients with AF. The preponderance of evidence from randomized trials and observational studies attests to higher bleeding rates among elderly individuals with AF.... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840349 Tue, 29 Sep 2009 16:47:21 +0100 2840349 http://www.medworm.com/index.php?rid=2840348&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240014 Semin Thromb Hemost 2009; 35: 543-547DOI: 10.1055/s-0029-1240014ABSTRACTAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a high risk of embolic stroke (cause in 15% of all strokes and 30% of strokes in those >75 years of age). Anticoagulation with warfarin will reduce stroke risk by about two thirds. The main risks of anticoagulation, namely bleeding, can be minimized by maintaining anticoagulation control within the international normalized range range of 2.0 to 3.0 (target: 2.5). To have a public health impact, patients with AF need efficient and correct identification, with appropriate treatment directed at those patients at most risk from the condition.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840348 Tue, 29 Sep 2009 16:47:21 +0100 2840348 http://www.medworm.com/index.php?rid=2840347&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240013 Semin Thromb Hemost 2009; 35: 527-542DOI: 10.1055/s-0029-1240013ABSTRACTDespite overwhelming evidence of the benefits of risk-adjusted oral anticoagulation on stroke reduction in patients with atrial fibrillation (AF), there is still considerable undertreatment. A multidisciplinary expert group was formed to discuss issues surrounding anticoagulant treatment of patients with AF to try and achieve consensus on various aspects of the implementation of guidelines on oral anticoagulation therapy in AF. Panel members were cardiologists, hematologists, and laboratory and primary care physicians with specific expertise from Europe and the United States. One of the most important conclusions of the meeting was to enhance guideline adherence by better communication of the data showing that the bene... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840347 Tue, 29 Sep 2009 16:47:21 +0100 2840347 http://www.medworm.com/index.php?rid=2840346&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240012 Semin Thromb Hemost 2009; 35: 525-526DOI: 10.1055/s-0029-1240012© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2840346 Tue, 29 Sep 2009 00:48:45 +0100 2840346 http://www.medworm.com/index.php?rid=2776288&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234147 Semin Thromb Hemost 2009; 35: 515-524DOI: 10.1055/s-0029-1234147ABSTRACTAtrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists. Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux). These drugs have minimal protein binding and predictable pharmacokinetics that allow fixed dosing without la... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776288 Wed, 09 Sep 2009 16:37:02 +0100 2776288 http://www.medworm.com/index.php?rid=2776287&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234146 Semin Thromb Hemost 2009; 35: 505-514DOI: 10.1055/s-0029-1234146ABSTRACTA patent foramen ovale (PFO) enables a right-to-left shunt in about a quarter of the population. The marked association between cryptogenic stroke and PFO supports the hypothesis that paradoxical embolism could be a relevant cause of stroke. Although this association has been described in several studies for patients <55 years of age, only limited data are available on the role of PFO in older patients. Recent studies, however, have also shown a significant association between cryptogenic stroke and PFO in patients >55 years of age. The relationship is especially marked in the presence of atrial septum aneurysm (ASA). This finding is in accordance with previous reports indicating that PFO and concomitant ASA is a... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776287 Wed, 09 Sep 2009 16:37:02 +0100 2776287 http://www.medworm.com/index.php?rid=2776286&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234145 This article focuses on this prothrombotic state and discusses the risk of thromboembolic events, pathophysiological mechanisms, and the potential role of anticoagulant treatment.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776286 Wed, 09 Sep 2009 16:37:02 +0100 2776286 http://www.medworm.com/index.php?rid=2776285&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234144 This article reviews the definitions, mechanisms of production, and links with pathophysiology of MPs in arterial disease, and thus whether or not they can contribute to improved patient care.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776285 Wed, 09 Sep 2009 16:37:02 +0100 2776285 http://www.medworm.com/index.php?rid=2776284&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234143 Semin Thromb Hemost 2009; 35: 478-487DOI: 10.1055/s-0029-1234143ABSTRACTSeveral endocrine disorders have been associated with an increased risk of cardiovascular disease (CVD) and mortality. In addition, even subtle hormonal disturbances may modulate the function of cardiovascular organs. In this article, we discuss in detail the contribution of thyroid hormones, cortisol, the somatotropic hormones, and prolactin in the development of CVD. We do not only discuss epidemiological evidence on the association between hormones and cardiovascular disease, but we also address possible pathophysiological mechanisms underlying this association. In fact, hormones can contribute to the development of CVD both indirectly by inducing secondary metabolic changes such as hypertension, insulin resistance,... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776284 Wed, 09 Sep 2009 16:37:02 +0100 2776284 http://www.medworm.com/index.php?rid=2776283&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234142 Semin Thromb Hemost 2009; 35: 468-477DOI: 10.1055/s-0029-1234142ABSTRACTIn this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, α2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibri... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776283 Wed, 09 Sep 2009 16:37:02 +0100 2776283 http://www.medworm.com/index.php?rid=2776282&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234141 Semin Thromb Hemost 2009; 35: 458-467DOI: 10.1055/s-0029-1234141ABSTRACTThe development of occlusive arterial and venous disease is contingent on the formation of a fibrin mesh that occurs following tissue damage and activation of the coagulation system. Clinical evidence indicates that fibrin structure and function are important determinants of cardiovascular risk, and the difference between clots formed from plasma and from purified fibrinogen highlights the importance of plasma factors in determining final clot structure. Twin, family, and case-control studies indicate there is a significant genetic contribution to variance in coagulation and fibrinolytic factors that may influence clot structure. Additionally, studies indicate a smaller but significant genetic contribution to fibrin st... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776282 Wed, 09 Sep 2009 16:37:02 +0100 2776282 http://www.medworm.com/index.php?rid=2776281&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234140 Semin Thromb Hemost 2009; 35: 451-457DOI: 10.1055/s-0029-1234140ABSTRACTThe metabolic syndrome is a cluster of risk factors for atherosclerosis. Although a universally accepted definition is still lacking because available classifications present slightly different diagnostic criteria, the metabolic syndrome is now recognized as a serious public health problem that affects up to 45% of the population >50 years of age in the United States and ~20 to 25% of the adult population in Europe.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776281 Wed, 09 Sep 2009 16:37:02 +0100 2776281 http://www.medworm.com/index.php?rid=2776280&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1234148 Semin Thromb Hemost 2009; 35: 449-450DOI: 10.1055/s-0029-1234148© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2776280 Wed, 09 Sep 2009 16:37:02 +0100 2776280 http://www.medworm.com/index.php?rid=2596030&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1226014 Semin Thromb Hemost 2009; 35: 447-447DOI: 10.1055/s-0029-1226014© Thieme Medical PublishersGet connected:Table of contents  |  FREE: Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596030 Tue, 14 Jul 2009 11:04:01 +0100 2596030 http://www.medworm.com/index.php?rid=2596029&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225766 Semin Thromb Hemost 2009; 35: 439-446DOI: 10.1055/s-0029-1225766ABSTRACTAll vitamin K–dependent coagulation factors require normal function of γ-glutamyl carboxylase and vitamin K epoxide reductase enzyme complex (VKORC1). Heritable dysfunction of γ-glutamyl carboxylase or of the VKORC1 complex results in the secretion of poorly carboxylated vitamin K–dependent proteins that play a role in coagulation. The following review will summarize the clinical manifestations of vitamin K–dependent coagulation factors deficiency I and II and will provide a detailed explanation about the gene and protein structure, the function of the protein, and an analysis of the previously reported mutations. Laboratory assays used for diagnosis will be discussed, and treatment for vari... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596029 Tue, 14 Jul 2009 11:04:01 +0100 2596029 http://www.medworm.com/index.php?rid=2596028&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225765 Semin Thromb Hemost 2009; 35: 426-438DOI: 10.1055/s-0029-1225765ABSTRACTFactor XIII (FXIII) is a tetrameric zymogen (FXIII-AB) that is converted into an active transglutaminase (FXIIIa) by thrombin and Ca in the terminal phase of the clotting cascade. By cross-linking fibrin chains and α plasmin inhibitor to fibrin, FXIIIa mechanically stabilizes fibrin and protects it from fibrinolysis. Severe deficiency of the potentially active A subunit (FXIII-A) is a rare but severe hemorrhagic diathesis. Delayed umbilical stump bleeding is characteristic, and subcutaneous, intramuscular, and intracranial bleeding occurs with a relatively high frequency in nonsupplemented patients. In addition, impaired wound healing and spontaneous abortion in women are also features of FXIII deficiency. The ext... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596028 Tue, 14 Jul 2009 11:04:01 +0100 2596028 http://www.medworm.com/index.php?rid=2596027&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225764 Semin Thromb Hemost 2009; 35: 416-425DOI: 10.1055/s-0029-1225764ABSTRACTSevere factor XI (FXI) deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide. In the past two decades, more than 180 mutations in the FXI gene have been reported in patients with FXI deficiency, five of which show a founder effect (Cys38Arg, Gln88Stop, Cys128Stop, Glu117stop, and Phe283Leu, the last two largely prevalent among Ashkenazi Jews). Inhibitors to FXI after exposure to plasma, FXI concentrates, or Rh immunoglobulin were described in patients with mutations resulting in null alleles. Treatment with low-dose recombinant activated factor VII in these patients appears promising. Survival advantages to patients with severe FXI have been recently reported. Herein, we present ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596027 Tue, 14 Jul 2009 11:04:01 +0100 2596027 http://www.medworm.com/index.php?rid=2596026&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225763 Semin Thromb Hemost 2009; 35: 407-415DOI: 10.1055/s-0029-1225763ABSTRACTFactor X (FX) deficiency is a rare, recessively inherited bleeding disorder representing 10% of all rare bleeding diseases and affecting 1 in every 1,000,000 people. Its clinical presentation places FX deficiency among the most severe of the rare coagulation defects, typically including hemarthroses, hematomas, and umbilical cord, gastrointestinal, and central nervous system bleeding. Phenotype diagnosis is based on the concomitant prolongation of the prothrombin time and activated partial thromboplastin time. Through the measurement of plasma level of FX antigen and its coagulant activity, two main types of deficiency can be distinguished: type I (concomitantly low levels of activity and antigen) and type II (low coag... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596026 Tue, 14 Jul 2009 11:04:01 +0100 2596026 http://www.medworm.com/index.php?rid=2596025&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225762 Semin Thromb Hemost 2009; 35: 400-406DOI: 10.1055/s-0029-1225762ABSTRACTThe complex formed between the procoagulant serine protease activated factor VII (FVII) and the membrane protein tissue factor, exposed on the vascular lumen upon injury, triggers the initiation of blood clotting. This review describes the clinical picture of FVII deficiency and provides information on diagnosis and management of the disease. FVII deficiency, the most common among the rare congenital coagulation disorders, is transmitted with autosomal recessive inheritance. Clinical phenotypes range from asymptomatic condition, even in homozygotes, to severe disease characterized by life-threatening and disabling symptoms (central nervous system and gastrointestinal bleeding and hemarthrosis), with early age of presen... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596025 Tue, 14 Jul 2009 11:04:01 +0100 2596025 http://www.medworm.com/index.php?rid=2596024&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225761 Semin Thromb Hemost 2009; 35: 390-399DOI: 10.1055/s-0029-1225761ABSTRACTCombined deficiency of factor V (FV) and factor VIII (FVIII) (F5F8D, or FV+FVIII) is a autosomal recessive bleeding disorder caused by mutations in genes encoding two components of the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC-53), that is, lectin mannose binding protein () and multiple coagulation factor deficiency 2 (), involved in the FV and FVIII intracellular transport rather than by DNA defects in the genes that encode the corresponding coagulation factors. F5F8D is estimated to be extremely rare (1:1,000,000) in the general population, but an increased frequency is observed in regions where consanguineous marriages are practiced. F5F8D is characterized by concomitantly low levels (usually ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596024 Tue, 14 Jul 2009 11:04:01 +0100 2596024 http://www.medworm.com/index.php?rid=2596023&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225760 This article will provide a concise description of the FV protein and gene and will review the molecular, clinical, and therapeutic aspects of FV deficiency.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596023 Tue, 14 Jul 2009 11:04:01 +0100 2596023 http://www.medworm.com/index.php?rid=2596022&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225759 Semin Thromb Hemost 2009; 35: 367-381DOI: 10.1055/s-0029-1225759ABSTRACTProthrombin deficiency is among the rarest inherited coagulation disorders, with a prevalence of ~1:2,000,000. Two main phenotypes can be distinguished: (1) hypoprothrombinemia (type I deficiency), characterized by concomitantly low levels of activity and antigen; and (2) dysprothrombinemia (type II deficiency), characterized by the normal or near-normal synthesis of a dysfunctional protein. In some cases, hypoprothrombinemia associated with dysprothrombinemia was also described in compound heterozygous defects. No living patient with undetectable plasma prothrombin has been reported to date. Prothrombin is encoded by a gene of ~21 kb located on chromosome 11 and containing 14 exons. Forty different mutations have been... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596022 Tue, 14 Jul 2009 11:04:01 +0100 2596022 http://www.medworm.com/index.php?rid=2596021&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225758 Semin Thromb Hemost 2009; 35: 356-366DOI: 10.1055/s-0029-1225758ABSTRACTInherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both (hypodysfibrinogenemia). Most often, patients with congenital fibrinogen disorders suffer from a bleeding diathesis but paradoxically may undergo severe thrombotic episodes. Pregnancy loss is another common clinical complication. Even in specialized laboratories, the precise diagnosis of some fibrinogen disorders may be challenging. Characterization of the molecular defect(s) is important as it provides a more accurate diagnosis, may enable prenatal diagnosis, will help elaborate a diagnostic strategy, and may distinguish in some cases those patie... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596021 Tue, 14 Jul 2009 11:04:01 +0100 2596021 http://www.medworm.com/index.php?rid=2596020&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225757 Semin Thromb Hemost 2009; 35: 349-355DOI: 10.1055/s-0029-1225757ABSTRACTRare bleeding disorders (RBDs) are autosomal recessive diseases including the inherited deficiencies of coagulation factors such as fibrinogen, factor (F) II, FV, FV + FVIII, FVII, FX, FXI, FXIII, and multiple deficiency of vitamin K–dependent factors, with clinical manifestations ranging from mild to severe. They represent 3 to 5% of all the inherited coagulation deficiencies with a prevalence in the general population varying between 1 in 500,000 and 1 in 2 million, being higher in areas where consanguineous marriages are diffuse. Despite the progress made in past years, as a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596020 Tue, 14 Jul 2009 11:04:01 +0100 2596020 http://www.medworm.com/index.php?rid=2596019&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1225756 Semin Thromb Hemost 2009; 35: 345-347DOI: 10.1055/s-0029-1225756© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2596019 Tue, 14 Jul 2009 00:45:14 +0100 2596019 http://www.medworm.com/index.php?rid=2419313&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222612 Semin Thromb Hemost 2009; 35: 337-343DOI: 10.1055/s-0029-1222612ABSTRACTHeparin is the second most widely used anticoagulant/antithrombotic agent besides warfarin and is commonly used for various purposes such as treatment and surgical indications. A significant adverse effect of heparin treatment can occur when heparin binds platelet factor 4 (H-PF4) to form a complex that results in formation of H-PF4 antibodies, which in turn leads to platelet/endothelial cell activation followed by heparin-induced thrombocytopenia (HIT). Based on the heparin-induced platelet aggregation and enzyme-linked immunosorbent assay tests, the H-PF4 antibody (HIT antibody) was diagnosed in 6% of Indian patients undergoing cardiovascular surgery who received unfractionated heparin, but the frequency of occurrenc... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419313 Tue, 19 May 2009 17:52:51 +0100 2419313 http://www.medworm.com/index.php?rid=2419312&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222611 This article aims to review the biological and clinical links between depression and cardiovascular disease.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419312 Tue, 19 May 2009 17:52:51 +0100 2419312 http://www.medworm.com/index.php?rid=2419311&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222610 Semin Thromb Hemost 2009; 35: 313-324DOI: 10.1055/s-0029-1222610ABSTRACTPsoriasis is a chronic inflammatory, immune-mediated skin disease affecting 2 to 3% of the general population and may cause significant quality-of-life impairment. Psoriasis and psoriatic arthritis are associated with increased atherothrombotic diseases, including myocardial infarction, deep venous thrombosis, and reduced life span. Both disease-specific and non–disease-specific risk factors are likely to fuel one another in deleterious vicious circles. Disease-specific risk factors are those that are a direct consequence of psoriasis inflammation and include hyperhomocysteinemia, elevated C-reactive protein, elevated blood inflammatory cytokines, and platelet hyperactivity. Non–disease-specific risk factor... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419311 Tue, 19 May 2009 17:52:51 +0100 2419311 http://www.medworm.com/index.php?rid=2419310&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222609 Semin Thromb Hemost 2009; 35: 307-312DOI: 10.1055/s-0029-1222609ABSTRACTIt is well known that the clinical phenotype of hemophilia may vary greatly among patients with the same apparent level of coagulation factor and the same genetic mutation. Thus, patients with severe hemophilia may experience a severe phenotype or only a milder bleeding tendency, suggesting some other moderating influence. To elucidate the mechanism of this heterogeneity, some investigators have recently suggested that inherited thrombophilic factors may play a role in the milder clinical presentation of severe hemophilia. In this review, we summarize current knowledge with respect to the modulation of the clinical phenotype of severe hemophilia by prothrombotic genetic risk factors. Although the published literature s... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419310 Tue, 19 May 2009 17:52:51 +0100 2419310 http://www.medworm.com/index.php?rid=2419309&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222608 This article reviews gender-specific differences in platelet function and response to aspirin. In contrast with men, women under 65 years of age do not benefit from aspirin therapy in primary prevention of coronary artery disease. Furthermore, the overall mortality after myocardial infarction is higher among women, which cannot simply be explained by age or individual treatment. Platelets play a central role in thrombo-ischemic events leading to myocardial infarction and ischemic stroke. Gender differences in platelet reactivity and “aspirin resistance” have been reported. Several studies using female platelets have shown increased platelet reactivity at baseline and a less effective inhibition of platelet aggregation by aspirin. The mechanisms underlying these differences are ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419309 Tue, 19 May 2009 17:52:51 +0100 2419309 http://www.medworm.com/index.php?rid=2419308&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222607 Semin Thromb Hemost 2009; 35: 288-294DOI: 10.1055/s-0029-1222607ABSTRACTThyroid hormones exert various effects on the hemostatic system, as documented by the fact that subclinical or overt thyroid dysfunctions may be associated with hypocoagulable or hypercoagulable states. In this review, the hemostatic balance (primary hemostasis, coagulation factors, and fibrinolytic system) in different thyroid disorders is analyzed from a laboratory, pathogenic, and clinical point of view. Although limited, the published studies suggest that patients with hyperthyroidism or subclinical hypothyroidism have an increased thrombotic risk, whereas patients with overt hypothyroidism have a bleeding tendency. Further trials on larger series of patients are needed to confirm these preliminary findings and to ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419308 Tue, 19 May 2009 17:52:51 +0100 2419308 http://www.medworm.com/index.php?rid=2419307&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222606 Semin Thromb Hemost 2009; 35: 277-287DOI: 10.1055/s-0029-1222606ABSTRACTNonalcoholic fatty liver disease (NAFLD), comprising its whole spectrum of conditions ranging from simple steatosis to steatohepatitis (nonalcoholic steatohepatitis; NASH) and cirrhosis, is the most frequent liver disease in developed countries and is now regarded as the liver manifestation of the metabolic syndrome. Several studies indicate that NAFLD, especially in its necro-inflammatory form (NASH), is associated with a systemic proinflammatory/prothrombotic state, independently of shared metabolic risk factors. This suggests that NAFLD/NASH is not simply a marker of the proinflammatory/prothrombotic state in the metabolic syndrome but is actively involved in its pathogenesis, possibly through the systemic release o... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419307 Tue, 19 May 2009 17:52:51 +0100 2419307 http://www.medworm.com/index.php?rid=2419306&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222605 Semin Thromb Hemost 2009; 35: 269-276DOI: 10.1055/s-0029-1222605ABSTRACTSome of the benefits of physical activity may result from effects on hemostasis. However, the increased burden of cardiovascular complications and sudden death occurring during and immediately after exercise prompts investigation to elucidate the biological relationship between physical exercise and hemostatic function. Although both the hemostatic and fibrinolytic systems are strongly influenced by physical exercise, the outcomes of available studies to date are biased by several confounding variables, including the subjects investigated, the type, intensity, and duration of the exercise, and the methods used for hemostatic evaluation. Considering these variables and attempting to synthesize the available data, it see... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419306 Tue, 19 May 2009 17:52:51 +0100 2419306 http://www.medworm.com/index.php?rid=2419305&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222604 Semin Thromb Hemost 2009; 35: 261-268DOI: 10.1055/s-0029-1222604ABSTRACTThrombosis is a major cause of morbidity and mortality in Western countries and is associated with a range of chronic diseases such as cardiovascular disease, renal disease, diabetes, and various autoimmune conditions. Improved health care and approaches to the treatment of disease are leading to aging populations that will probably result in an increase in the incidence of thrombosis and associated manifestations over the next few decades. Adopting a physically active lifestyle through regular exercise has been proposed to lower the risk of developing thrombosis. Indeed, it has been demonstrated that exercise is beneficial for health, although there is inconsistent data from studies investigating the effect of exercis... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419305 Tue, 19 May 2009 17:52:51 +0100 2419305 http://www.medworm.com/index.php?rid=2419304&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222603 Semin Thromb Hemost 2009; 35: 257-259DOI: 10.1055/s-0029-1222603© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419304 Tue, 19 May 2009 17:52:51 +0100 2419304 http://www.medworm.com/index.php?rid=2419303&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1222602 Semin Thromb Hemost 2009; 35: 255-255DOI: 10.1055/s-0029-1222602© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2419303 Tue, 19 May 2009 00:58:12 +0100 2419303 http://www.medworm.com/index.php?rid=2384112&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220785 Semin Thromb Hemost 2009; 35: 242-254DOI: 10.1055/s-0029-1220785ABSTRACTThe major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades have not been adequately translated to clinical laboratory diagnosis. Hereditary platelet function disorders (PFDs) are at least as prevalent in the general population as von Willebrand disease (VWD) although PFDs tend not be as well recognized or evaluated. Clinical mucous and skin bleeding in patients with PFDs is prototypic of primary hemostasis disorders, and the bleeding pattern is not distinguishable from that of other primary hemostasis disorders such as VWD. However, different treatment needs, between these discrete disorders, make a precise diagnosis mandatory. Currently, clinicians re... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384112 Sun, 03 May 2009 21:10:49 +0100 2384112 http://www.medworm.com/index.php?rid=2384111&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220331 Semin Thromb Hemost 2009; 35: 233-241DOI: 10.1055/s-0029-1220331ABSTRACTActivated platelets contribute to the arrest of bleeding by forming aggregates at sites of vascular injury and by providing a surface for assembling enzyme complexes involved in fibrin formation (platelet procoagulant activity; PCA). Impairment in the latter property of platelets has been observed in some disorders of hemostasis. In Scott syndrome, there is a defect in membrane vesiculation and in the surface expression of phosphatidylserine (PS), the phospholipid that is necessary for assembling the factor VIIIa/IXa (tenase) and factor Va/Xa (prothrombinase) complexes involved in thrombin formation. A family with an isolated defect in vesiculation, but normal prothrombinase activity, has also been reported. In the Que... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384111 Sun, 03 May 2009 21:10:49 +0100 2384111 http://www.medworm.com/index.php?rid=2384110&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220330 Semin Thromb Hemost 2009; 35: 224-232DOI: 10.1055/s-0029-1220330ABSTRACTPlatelet glycoproteins subserve a wide variety of critical functions in blood platelets. Congenital deficiencies or functional abnormalities in platelet glycoproteins may produce serious bleeding disorders such as Glanzmann thrombasthenia or Bernard-Soulier syndrome. Other hematologic disorders, such as Fanconi anemia and various myelodysplastic syndromes, may also be associated with abnormalities in platelet glycoproteins. Additionally, several acquired disorders involving the major platelet glycoproteins are increasingly being recognized. The large number of techniques, now available to characterize platelet glycoprotein disorders, reflect the many advances in biochemistry, molecular analysis, flow cytometry, and, mo... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384110 Sun, 03 May 2009 21:10:49 +0100 2384110 http://www.medworm.com/index.php?rid=2384109&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220329 Semin Thromb Hemost 2009; 35: 213-223DOI: 10.1055/s-0029-1220329ABSTRACTThe electron microscope has proved to be a useful tool to study and understand the biology of platelets and to classify many platelet disorders. After a technical overview, this article reviews syndromes originating from platelet organelle, cytoskeleton, and membrane defects for which electron microscopy plays a role in the diagnostic process, such as gray platelet syndrome, Paris-Trousseau syndrome, storage pool diseases, MYH9-related thrombocytopenias, or Wiskott-Aldrich syndrome. Particular focus is given to the ultrastructural aspect of platelets in these disorders.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384109 Sun, 03 May 2009 21:10:49 +0100 2384109 http://www.medworm.com/index.php?rid=2384108&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220328 Semin Thromb Hemost 2009; 35: 204-212DOI: 10.1055/s-0029-1220328ABSTRACTInherited disorders of platelets give rise to rare bleeding syndromes through defects of platelet function and/or platelet production. Platelet function testing by biological and immunologic assays can identify the loss or abnormal functioning of specific receptor systems, signaling pathways, storage organelles, or enzymatic activities essential for adhesion, activation, and aggregation. In vitro culture of megakaryocytes can help identify the origin of familial thrombocytopenias, and electron microscopy can point to ultrastructural defects and giant platelet syndromes. But a full diagnosis can only be complete when the genetic defect has been defined for each patient. Glanzmann thrombasthenia (GT) and the Bernard-Soul... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384108 Sun, 03 May 2009 21:10:49 +0100 2384108 http://www.medworm.com/index.php?rid=2384107&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220327 Semin Thromb Hemost 2009; 35: 189-203DOI: 10.1055/s-0029-1220327ABSTRACTMyosin heavy chain 9 (MYH9)-related platelet disorders belong to the group of inherited thrombocytopenias. The MYH9 gene encodes the nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cytoskeletal contractile protein. Several mutations in the MYH9 gene lead to premature release of platelets from the bone marrow, macrothrombocytopenia, and cytoplasmic inclusion bodies within leukocytes. Four overlapping syndromes, known as May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian platelet syndrome, describe different clinical manifestations of MYH9 gene mutations. Macrothrombocytopenia is present in all affected individuals, whereas only some develop additional clinical manifestations such as renal failure, h... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384107 Sun, 03 May 2009 21:10:49 +0100 2384107 http://www.medworm.com/index.php?rid=2384106&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220326 Semin Thromb Hemost 2009; 35: 181-188DOI: 10.1055/s-0029-1220326ABSTRACTInvestigation of platelet function disorders in infants and small children requires the collaborative efforts of clinicians and clinical laboratories. A detailed personal, family, and medication history, and a search for additional clinical phenomena may help to direct diagnostic laboratory investigations. Testing for these disorders in young children presents several challenges: the requirement of relatively large volumes of blood, lack of standardization, and the absence of well-established age-specific reference ranges. Neonates show the most notable differences in platelet function compared to older children and adults; the decreased platelet activation responses persist for the first 2 to 4 weeks after delivery. S... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384106 Sun, 03 May 2009 21:10:49 +0100 2384106 http://www.medworm.com/index.php?rid=2384105&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220325 This article will also discuss other whole blood testing processes for assessing platelet function, particularly as applied to assessing the effect of antiplatelet medication.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384105 Sun, 03 May 2009 21:10:49 +0100 2384105 http://www.medworm.com/index.php?rid=2384104&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220324 Semin Thromb Hemost 2009; 35: 158-167DOI: 10.1055/s-0029-1220324ABSTRACTLight transmission aggregometry (LTA) is the gold standard for the study of patients with defects of platelet function. Use of LTA in clinical practice for predicting the risk of thrombosis or monitoring the pharmacologic effects of antiplatelet agents should be discouraged, because not only is the monitoring of treatment with antiplatelet agents (with any laboratory test) not indicated at present, but also the lack of standardization of the technique for LTA makes it additionally unsuitable for this purpose. The need for standardization of LTA has recently been emphasized by the results of four surveys, which showed that there is a wide variation in the methodology used worldwide. A modification of the traditional LTA... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384104 Sun, 03 May 2009 21:10:49 +0100 2384104 http://www.medworm.com/index.php?rid=2384102&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220323 Semin Thromb Hemost 2009; 35: 150-157DOI: 10.1055/s-0029-1220323ABSTRACTGlobal tests of platelet function are often used as screening tests during the laboratory investigation of individuals with suspected hemostatic defects. Because global tests of platelet function do not enable specific diagnosis of platelet disorders, they are normally performed as the first part of a two-step strategy that requires further testing with more specialized assays of platelet function to confirm or refute the diagnosis. The most commonly proposed rationale for testing global platelet function as a first-line investigation is that normal test results may exclude a diagnosis of platelet function disorder so that further specialized testing can be avoided. For this reason, global platelet function tests are u... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384102 Sun, 03 May 2009 21:10:49 +0100 2384102 http://www.medworm.com/index.php?rid=2384100&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220322 Semin Thromb Hemost 2009; 35: 139-149DOI: 10.1055/s-0029-1220322ABSTRACTInternal quality control (IQC) and external quality assurance (EQA) are distinct processes that contribute to ensure the overall quality (i.e., correctness) of laboratory test procedures. This review summarizes the current position of IQC and EQA in platelet function testing. These processes are in their infancy for these tests, despite the many years in which these tests have been performed within diagnostic hemostasis laboratories. This is understandable, due to the many challenges imposed by the requirements of the tests themselves and of the IQC and EQA processes, namely the regular availability, and ongoing supply and transport, of fresh blood containing functional platelets for testing within a very short time fr... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384100 Sun, 03 May 2009 21:10:49 +0100 2384100 http://www.medworm.com/index.php?rid=2384099&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220321 Semin Thromb Hemost 2009; 35: 131-138DOI: 10.1055/s-0029-1220321ABSTRACTThe platelet disorders are a group of heterogeneous, congenital and acquired bleeding disorders associated with impaired platelet function. There is a growing interest in standardizing the assessment of these disorders, but this is challenged by their heterogeneity, the absence of widely accepted diagnostic criteria, and inconsistency in laboratory testing practices for platelet disorders. Symptoms commonly associated with platelet disorders include rapid-onset bleeding with hemostatic challenges, peripartum bleeding, menorrhagia, epistaxis, gingival bleeding, and increased bruising. Attempts have been made to standardize the assessment of these symptoms, using clinical tools and bleeding scores. However, there are cur... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384099 Sun, 03 May 2009 21:10:49 +0100 2384099 http://www.medworm.com/index.php?rid=2384098&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1220320 Semin Thromb Hemost 2009; 35: 127-130DOI: 10.1055/s-0029-1220320© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2384098 Sun, 03 May 2009 21:10:49 +0100 2384098 http://www.medworm.com/index.php?rid=2288580&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214155 Semin Thromb Hemost 2009; 35: 119-126DOI: 10.1055/s-0029-1214155The publisher regrets errors in the above article as originally printed in Seminars in Thrombosis and Hemostasis, Volume 34, Number 7, 2008, pp 635–641.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  FREE: Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288580 Wed, 25 Mar 2009 22:58:36 +0100 2288580 http://www.medworm.com/index.php?rid=2288579&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214154 Semin Thromb Hemost 2009; 35: 111-118DOI: 10.1055/s-0029-1214154ABSTRACTHyperglycemia and insulin resistance are independent risk factors for cardiovascular disease (CVD). Postprandial glycemic “spikes” adversely affect vascular structure and function via multiple mechanisms including oxidative stress, inflammation, low-density lipoprotein oxidation, protein glycation, and procoagulant activity. Glycemic responses can be reliably predicted by considering both the quantity and quality of carbohydrate. The glycemic index (GI), a measure of carbohydrate quality, has provided insights that knowledge of the sugar or starch content has not. In prospective observational studies, dietary GI and/or glycemic load (GL; the product of the amount of carbohydrate and GI) independently predic... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288579 Wed, 25 Mar 2009 22:58:36 +0100 2288579 http://www.medworm.com/index.php?rid=2288578&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214153 Semin Thromb Hemost 2009; 35: 104-110DOI: 10.1055/s-0029-1214153ABSTRACTThrombin plays an important role in hemostasis through its multiple functions across blood coagulation, platelet activation, and fibrinolysis. The measurement of thrombin generation is therefore viewed as a potentially useful test that could be applied to the screening, monitoring, and/or diagnosis of hemostatic abnormalities. Indeed, advances in thrombin generation assays have created significant interest and debate as to whether they may provide a more physiologically relevant testing system than do traditional coagulation tests. A variety of thrombin generation assays, including commercially available systems, have been investigated for their correlation with hypocoagulable and hypercoagulable states. Although there... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288578 Wed, 25 Mar 2009 22:58:36 +0100 2288578 http://www.medworm.com/index.php?rid=2288577&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214152 Semin Thromb Hemost 2009; 35: 093-103DOI: 10.1055/s-0029-1214152ABSTRACTProcoagulant toxins are important hemotoxins that have been investigated both as laboratory reagents and potential therapeutic agents. In human envenomation by some elapid and many viperid snakes, these toxins result in venom-induced consumption coagulopathy. Overall, the coagulant activity of the various venoms is difficult to characterize, and many studies simply characterize toxin conversion of isolated substrates, such as the effect of a snake toxin on purified fibrinogen, or on multiple single substrates. As the full effects of toxins on the coagulation pathway are rarely examined, even in vitro, our understanding of the pathophysiology of envenoming is limited. Although prothrombin activators cause a single effec... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288577 Wed, 25 Mar 2009 22:58:36 +0100 2288577 http://www.medworm.com/index.php?rid=2288575&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214151 Semin Thromb Hemost 2009; 35: 081-092DOI: 10.1055/s-0029-1214151ABSTRACTAs monogenic disorders, hemophilia A and B are compelling candidates for treatment with gene therapy. In hemophilia, a therapeutic benefit achieved by gene therapy should only require a modest increase in the endogenous factor level; response to treatment can be monitored easily; and there are relevant small and large animal models. The two main approaches aiming to restore factor VIII or factor IX production are based on genetically modified cells or direct in vivo gene delivery using viral or plasmid vectors. The progress toward gene therapy for hemophilia A and B in both preclinical and clinical models will be evaluated in this review. Various viral and nonviral vectors are discussed in the context of current hurdle... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288575 Wed, 25 Mar 2009 22:58:36 +0100 2288575 http://www.medworm.com/index.php?rid=2288573&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214150 This article summarizes the current knowledge on the use of this technique in patients with inhibitors against coagulation factors. Overall, the published literature documents that extracorporeal immunoadsorption is a safe and useful technique for the elimination of coagulation inhibitors. However, further randomized clinical trials are needed to better assess the cost-effectiveness of such procedures.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288573 Wed, 25 Mar 2009 22:58:36 +0100 2288573 http://www.medworm.com/index.php?rid=2288571&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214149 This article reviews current thoughts and alternatives to the classic approach of the classification and functional characterization of VWD. Of particular interest to this author is the utility of an extended core test panel that includes additional functional VWF assays, such as the collagen binding assay, and the potential for desmopressin (DDAVP) challenge to not only provide therapeutic information but also assist in the better characterization of individuals with defects or deficiencies in von Willebrand factor (VWF). The potential use of supplementary assays such as the PFA-100 and the VWF propeptide assay after DDAVP challenge is also worth noting.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and H... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288571 Wed, 25 Mar 2009 22:58:36 +0100 2288571 http://www.medworm.com/index.php?rid=2288569&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214148 Semin Thromb Hemost 2009; 35: 050-059DOI: 10.1055/s-0029-1214148ABSTRACTD-dimer, the final degradation product of cross-linked fibrin, is typically elevated in patients with acute venous thromboembolism. With its high sensitivity and negative predictive value, D-dimer testing may have a role for ruling-out the diagnosis in patients with suspected deep vein thrombosis or pulmonary embolism. For this purpose, D-dimer testing has been integrated in sequential diagnostic strategies including those using pretest clinical probability assessment and imaging techniques. A large variety of assays are now available for D-dimer measurement, with different sensitivities and specificities for the diagnosis of venous thromboembolism. Attempts to standardize the various D-dimer assays have been made but ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288569 Wed, 25 Mar 2009 22:58:36 +0100 2288569 http://www.medworm.com/index.php?rid=2288567&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214147 Semin Thromb Hemost 2009; 35: 042-049DOI: 10.1055/s-0029-1214147ABSTRACTPharmacologic therapies are essential in the management of patients with hemostatic and thrombotic diseases because these therapies are able to modify components of the coagulation pathway and platelet response. Nevertheless, responses to different drugs vary significantly, and the best clinical outcome frequently involves a delicate risk/benefit balance. The recent exponential growth of pharmacogenomics has led to the emergence of individualized medicine that has revolutionized modern medical practice, allowing for a deeper understanding of pathophysiology, increased diagnostic specificity, and better markers for risk stratification and an enhanced potential for gene therapy. Management of drugs prescribed to treat th... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288567 Wed, 25 Mar 2009 22:58:36 +0100 2288567 http://www.medworm.com/index.php?rid=2288565&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214146 Semin Thromb Hemost 2009; 35: 034-041DOI: 10.1055/s-0029-1214146ABSTRACTThe treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these n... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288565 Wed, 25 Mar 2009 22:58:36 +0100 2288565 http://www.medworm.com/index.php?rid=2288563&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214145 Semin Thromb Hemost 2009; 35: 023-033DOI: 10.1055/s-0029-1214145ABSTRACTBiological rhythms are a universal phenomenon in living organisms and serve to help organisms adapt within a circadian cycle to the 24-hour-oscillating environment. The rhythmic modulation of selective pathways thus enables organisms to optimize their ability to store and generate chemical energy, to minimize environmental stresses, and to reproduce by cycles of cell growth and division. Remarkably, the onset of both cardiovascular disorders and venous thromboembolism also undergoes circadian oscillations, which might be closely related to an internal biological clock. A highly repetitive rhythmic cycle seems to modulate platelet and endothelial functions, as well as the concentration and activity of several proteins o... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288563 Wed, 25 Mar 2009 22:58:36 +0100 2288563 http://www.medworm.com/index.php?rid=2288561&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214144 Semin Thromb Hemost 2009; 35: 009-022DOI: 10.1055/s-0029-1214144ABSTRACTHemostasis is traditionally defined as the physiologic process whereby bleeding is antagonized and possibly stopped to minimize blood loss. The first medical description of the clinical and inherited features of hemostasis can be dated back more than 1000 years, when Abu al-Qasim Khalaf ibn ‘Abbas al-Andalusi al-Zahrawi’ medical treatise provided some initial insights into this puzzling process. Since then, continuous and revolutionary scientific developments have contributed to decoding several aspects of this intricate but essential physiologic phenomenon, providing a reliable model to explain the leading mechanisms involved. Although the point at which bleeding stops is commonly referred to as “coa... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288561 Wed, 25 Mar 2009 22:58:36 +0100 2288561 http://www.medworm.com/index.php?rid=2288559&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214143 Semin Thromb Hemost 2009; 35: 003-008DOI: 10.1055/s-0029-1214143© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288559 Wed, 25 Mar 2009 22:58:36 +0100 2288559 http://www.medworm.com/index.php?rid=2288557&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214142 Semin Thromb Hemost 2009; 35: 001-002DOI: 10.1055/s-0029-1214142© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2288557 Wed, 25 Mar 2009 22:58:36 +0100 2288557 http://www.medworm.com/index.php?rid=2184039&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145264 Semin Thromb Hemost 2008; 34: 803-803DOI: 10.1055/s-0029-1145264© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184039 Sat, 14 Feb 2009 03:48:21 +0100 2184039 http://www.medworm.com/index.php?rid=2184038&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145252 Semin Thromb Hemost 2008; 34: 703-707DOI: 10.1055/s-0029-1145252© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184038 Sat, 14 Feb 2009 03:48:21 +0100 2184038 http://www.medworm.com/index.php?rid=2184037&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145261 Semin Thromb Hemost 2008; 34: 794-802DOI: 10.1055/s-0029-1145261ABSTRACTAntiphospholipid syndrome (APS) represents a serious risk factor in pregnancy resulting in several complications, leading to fetal loss and hemostatic complications. In this dedicated report, we describe our experiences in the treatment of pregnancies in patients with APS. The retrospective data from 140 pregnant women were investigated, and the treatment results of 121 patients were recorded. We studied two groups of patients receiving different treatment. The first group ( = 78) received the standard therapy with low-weight-molecular heparin (dalteparin 5000 U or certoparin 3000 U daily) and aspirin (100 mg daily) and in the second group ( = 43) an additional 0.2 g/kg intravenous immunoglobuli... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184037 Sat, 14 Feb 2009 03:48:21 +0100 2184037 http://www.medworm.com/index.php?rid=2184036&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145260 Semin Thromb Hemost 2008; 34: 779-793DOI: 10.1055/s-0029-1145260ABSTRACTAnticoagulant drugs are the most frequently hospital-prescribed compounds in many countries and are used with the intention to prevent and treat venous and arterial thromboembolism. Because of side effects and the necessity of dose adjustment of unfractionated heparins and coumarins, low-molecular-weight heparins, heparinoids, and direct systemically applied thrombin inhibitors were developed. Because of limitations of these anticoagulants, synthetic indirect and direct factor Xa inhibitors and direct thrombin inhibitors were further developed with the aim to improve the benefit/risk ratio for anticoagulant therapy of patients using a simplified mode of action. This overview describes the results of some recent studies... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184036 Sat, 14 Feb 2009 03:48:21 +0100 2184036 http://www.medworm.com/index.php?rid=2184035&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145259 Semin Thromb Hemost 2008; 34: 772-778DOI: 10.1055/s-0029-1145259ABSTRACTProfessor Eberhard F. Mammen greatly contributed to the understanding of the relationship between hemostatic abnormalities and liver diseases. The physiology of the hemostatic system is closely linked to liver function because the liver parenchymal cells produce most of the factors of the clotting and fibrinolytic systems. Acute or chronic hepatocellular diseases and hepatic failure including liver cirrhosis, vitamin K deficiency, liver surgery including liver transplantation, and sclerotherapy of bleeding esophageal varices, which were classified by Prof. Mammen, show various hemostatic abnormalities in the coagulation system, fibrinolytic system, platelets, and the reticuloendothelial system. Hemostatic abnormalities... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184035 Sat, 14 Feb 2009 03:48:21 +0100 2184035 http://www.medworm.com/index.php?rid=2184034&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145258 Semin Thromb Hemost 2008; 34: 762-771DOI: 10.1055/s-0029-1145258ABSTRACTThe risk of bleeding associated with antithrombotic and fibrinolytic therapy depends on factors that are specific for the drugs and the patients. In this narrative review, we describe the most important risk factors for bleeding for each class of drugs. Pertinent examples are recent initiation of therapy with vitamin K antagonists, low-molecular-weight heparins, and renal dysfunction, and higher dose of aspirin. However, for every class of drug, there are also examples that are more controversial. Knowledge of these risk factors helps to weigh the risk and benefit in the selection of therapy in individual patients. Moreover, some risk factors can be modified or avoided if they are recognized.[...]© Thieme Medical Publ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184034 Sat, 14 Feb 2009 03:48:21 +0100 2184034 http://www.medworm.com/index.php?rid=2184033&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145257 Semin Thromb Hemost 2008; 34: 747-761DOI: 10.1055/s-0029-1145257ABSTRACTA comprehensive understanding of the pathogenesis of venous thrombosis is essential for identifying patients at increased risk and who may therefore benefit from more aggressive preventive and therapeutic measures. As for other pathologies, the pathogenesis of venous thromboembolism is multifactorial. All risk factors, either congenital or acquired, are relatively “innocent” when considered alone. However, when an individual is unlucky enough to inherit one or more abnormality, compounded in many cases by environmental hazards, that person may be propelled over a threshold that precipitates the development of thrombosis. An appropriate analogy is that where “the last drop makes the cup run over.&#8221... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184033 Sat, 14 Feb 2009 03:48:21 +0100 2184033 http://www.medworm.com/index.php?rid=2184032&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145256 Semin Thromb Hemost 2008; 34: 742-746DOI: 10.1055/s-0029-1145256ABSTRACTCurrent insights in the pathogenesis of multiple organ dysfunction in patients with sepsis point to a pivotal role of inflammation and coagulation. One of the most important mechanisms contributing to the activation of coagulation in sepsis is the downregulation of physiologic anticoagulant systems, such as the antithrombin pathway. More than 20 years ago, Eberhard Mammen already hypothesized that coagulation activation and antithrombin were important factors in patients with sepsis. Abundant experimental and clinical studies have supported that notion in recent years. The better understanding of the pathogenesis of coagulation activation and the role of natural anticoagulants in sepsis has led to the development of an... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184032 Sat, 14 Feb 2009 03:48:21 +0100 2184032 http://www.medworm.com/index.php?rid=2184031&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145255 Semin Thromb Hemost 2008; 34: 734-741DOI: 10.1055/s-0029-1145255ABSTRACTThe association of cancer and thrombosis has been known for nearly 150 years. Compared with patients without cancer, those with cancer have an increased risk of thrombosis and recurrent thrombosis. It is now well accepted that patients with idiopathic venous thromboembolism are also at increased risk of later being diagnosed with cancer. This is further confirmation of the intertwined nature of cancer and thrombosis. Although the mechanisms of this association are still under examination, much work has accrued over the past two decades to suggest an influence of thrombin on cancer biology. This review focuses on the important role of thrombin in cancer research; recent in vitro work illustrating the mechanisms by which... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184031 Sat, 14 Feb 2009 03:48:21 +0100 2184031 http://www.medworm.com/index.php?rid=2184030&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145254 This article reviews the history of the PFA-100 and details its clinical utility in several settings. The PFA-100 was first introduced to us in 1995 in an issue of which included data from a field trial headed by Dr. Eberhard Mammen. Since that time, the PFA-100 has featured in nearly 500 publications and some 35 reviews. The PFA-100 has potential utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (VWD) and various platelet disorders. The PFA-100 also has potential value for monitoring DDAVP (desmopressin) therapy in both VWD and functional platelet disorders. Most recent attention has focused on sensitivity to antiplatelet medication, where a new language has also emerged, with researchers talking about ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184030 Sat, 14 Feb 2009 03:48:21 +0100 2184030 http://www.medworm.com/index.php?rid=2184029&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145263 Semin Thromb Hemost 2008; 34: 701-701DOI: 10.1055/s-0029-1145263© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184029 Sat, 14 Feb 2009 03:48:21 +0100 2184029 http://www.medworm.com/index.php?rid=2184028&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145262 Semin Thromb Hemost 2008; 34: 699-699DOI: 10.1055/s-0029-1145262© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184028 Sat, 14 Feb 2009 03:48:21 +0100 2184028 http://www.medworm.com/index.php?rid=2184027&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145253 Semin Thromb Hemost 2008; 34: 697-698DOI: 10.1055/s-0029-1145253© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184027 Sat, 14 Feb 2009 03:48:21 +0100 2184027 http://www.medworm.com/index.php?rid=2184026&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1145251 Semin Thromb Hemost 2008; 34: 693-695DOI: 10.1055/s-0029-1145251© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2184026 Fri, 13 Feb 2009 02:55:06 +0100 2184026 http://www.medworm.com/index.php?rid=2040866&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104547 Semin Thromb Hemost 2008; 34: 683-691DOI: 10.1055/s-0028-1104547ABSTRACTMicroparticles (MPs) are small fragments of membrane-bound cytoplasm that are shed from the surface of an activated or apoptotic cell. Recently, their function as vectors of transcellular exchange of biologic information, in addition to better described forms of intercellular communication such as growth factors, cytokines, and chemokines, has become well recognized. Circulating levels of MPs are thought to reflect a balance between cell stimulation, proliferation, and death. The production of MPs is thought to predominately occur by vesiculation or blebbing of the cell membrane. The mechanisms governing the remodeling of the plasma membrane are complex, involving cytoskeletal changes and a shift from normal phospholip... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040866 Wed, 17 Dec 2008 13:33:16 +0100 2040866 http://www.medworm.com/index.php?rid=2040865&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104546 Semin Thromb Hemost 2008; 34: 670-682DOI: 10.1055/s-0028-1104546ABSTRACTThrombin generation is a key process that determines the extent of a hemostatic plug or a thrombotic process. The ensuing thrombin burst is crucial for the formation of a stable fibrin clot. During its active life, thrombin exerts a multitude of highly regulated actions on the blood and the vessel wall, including the clotting of fibrinogen. The inappropriate generation of thrombin may lead to pathologic processes, foremost of which are hemorrhagic or thrombotic diseases. The coagulation system is usually investigated by means of two in vitro classic clotting tests, the activated partial thromboplastin time (APTT) and prothrombin time (PT), which assess only time to initiation of clot formation and do not entirely refle... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040865 Wed, 17 Dec 2008 13:33:16 +0100 2040865 http://www.medworm.com/index.php?rid=2040864&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104545 Semin Thromb Hemost 2008; 34: 663-669DOI: 10.1055/s-0028-1104545ABSTRACTvon Willebrand factor (VWF) is a multimeric plasma protein that mediates platelet adhesion and aggregation at sites of vascular injury and also acts as a protective carrier of factor VIII. Although the acquired or inherited deficiency of VWF is associated with a bleeding tendency, there is increasing evidence that VWF also plays a pivotal role in thrombosis. The presence in plasma of unusually large VWF multimers, due to the congenital or acquired deficiency of the VWF-cleaving metalloproteinase ADAMTS13, has been implicated in the pathogenesis of thrombotic thrombocytopenic purpura. In addition, high plasma levels of VWF have been associated with an increased risk of atherothrombosis. The current article reviews the l... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040864 Wed, 17 Dec 2008 13:33:16 +0100 2040864 http://www.medworm.com/index.php?rid=2040863&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104544 This article reviews the clinical and laboratory approach to the diagnosis of patients presenting with MCB, the limitations of the available methodologies to evaluate the clinical significance of bleeding, and the diagnostic yield of global and specific hemostasis tests used to investigate these patients.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040863 Wed, 17 Dec 2008 13:33:16 +0100 2040863 http://www.medworm.com/index.php?rid=2040862&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104543 Semin Thromb Hemost 2008; 34: 647-653DOI: 10.1055/s-0028-1104543ABSTRACTPoint-of-care (POC) testing in the field of hemostasis is rapidly expanding in many countries. This includes use of global tests of hemostasis in operating theaters and especially use of POC monitors for determination of the international normalized ratio (INR) for monitoring oral anticoagulant therapy. Issues related to internal quality control and external quality assessment for these devices are reviewed. Data from external quality assessment exercises involving users of several different POC-INR devices is described, and use of split samples where a patient sample is analyzed by both a POC device and by a conventional laboratory method is described.[...]© Thieme Medical PublishersGet connected:Table of contents �... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040862 Wed, 17 Dec 2008 13:33:16 +0100 2040862 http://www.medworm.com/index.php?rid=2040861&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104542 Semin Thromb Hemost 2008; 34: 642-646DOI: 10.1055/s-0028-1104542ABSTRACTThe term in laboratory medicine refers to all the procedures commonly used in clinical laboratories to monitor the routine performance of testing processes, to detect possible errors, and to correct problems before test results are reported. In particular, internal quality control (IQC) and external quality assessment (EQA) programs are used to evaluate and improve quality in laboratory medicine. Laboratory testing is necessary for the diagnosis and treatment of patients with hemostatic disorders. However, whereas the benefits of quality control and quality assessment in hemostasis have been demonstrated many times and are well documented, available scientific evidence is significantly less than that in clinical chemis... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040861 Wed, 17 Dec 2008 13:33:16 +0100 2040861 http://www.medworm.com/index.php?rid=2040860&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104541 Semin Thromb Hemost 2008; 34: 635-641DOI: 10.1055/s-0028-1104541ABSTRACTThe two components of biological variability are interindividual variability, which is the variability due to the heterogeneity of physiologic influences among subjects, and intraindividual variability, which is due to the variability in the same individual over time. Analysis of biological variation is crucial for estimating the critical difference, which corresponds with a threshold suggestive of a statistically significant difference between two consecutive results of a laboratory parameter in the same subject and is therefore unlikely attributable to casual (random) oscillation of values. Studies on biological variation of tests of hemostasis are outdated, and the published results should be confirmed by using mode... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040860 Wed, 17 Dec 2008 13:33:16 +0100 2040860 http://www.medworm.com/index.php?rid=2040859&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104540 This article should be of interest to both laboratory scientists working in hemostasis and the clinicians that request such tests. The former, because these are ultimately responsible for the test results they provide to clinicians, and there is a duty of care to provide both accurate and precise results to enable clinicians to manage patients appropriately and to avoid the need to recollect and retest. The latter because unless clinicians gain an appreciation of these issues, they will not be in a position to best manage their patients.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040859 Wed, 17 Dec 2008 13:33:16 +0100 2040859 http://www.medworm.com/index.php?rid=2040858&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104539 Semin Thromb Hemost 2008; 34: 604-611DOI: 10.1055/s-0028-1104539ABSTRACTThe activated partial thromboplastin time (APTT) is the most common coagulation test procedure performed in routine laboratories, apart from the prothrombin time. The test is traditionally used for identifying quantitative and qualitative abnormalities in the intrinsic and common pathways of coagulation, monitoring anticoagulant therapy with unfractionated heparin, and detecting inhibitors of blood coagulation, the most common of which is the lupus anticoagulant. Whereas short APTT values have been mostly overlooked in the past, recent evidence suggests that these might be associated with hypercoagulability. Although clinical relevance is yet to be clearly defined, hypercoagulability detected by a shortened APTT appear... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040858 Wed, 17 Dec 2008 13:33:16 +0100 2040858 http://www.medworm.com/index.php?rid=2040857&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104538 We report our personal experience with use of some of these materials, as well as review alternate or supplementary procedures for calibration and/or validation of ISI and for determination and validation of MNPT. In brief, our data and experience suggests that further verification checks should be performed prior to acceptance of ISI and MNPT estimates generated from commercial reference-plasma calibration sets. We detail various strategies to ensure that laboratory practices are optimized to provide INRs that accurately reflect a patient's true anticoagulant status and to thus assist their clinical therapeutic management.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040857 Wed, 17 Dec 2008 13:33:16 +0100 2040857 http://www.medworm.com/index.php?rid=2040856&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104537 This article takes the reader through a journey of the history of the phenotypic tests for hemostasis and thrombosis starting from the most simple (which were based on the visual inspection and recording of the time needed for native whole blood to clot) to the more complex ones based on the addition to plasma of exogenous substances, use of sophisticated coagulometers or synthetic substrates, and use of computer software to record coagulation times or visualize coagulation tracings and thrombin generation curves. One can see how the simple tests evolved over the years and how such old and time-honored tests as thrombin generation and thromboelastography, devised more than 50 years ago and neglected for many years, are now gaining momentum thanks to the progress made by the technology comb... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040856 Wed, 17 Dec 2008 13:33:16 +0100 2040856 http://www.medworm.com/index.php?rid=2040855&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1104536 Semin Thromb Hemost 2008; 34: 579-583DOI: 10.1055/s-0028-1104536© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040855 Wed, 17 Dec 2008 13:33:16 +0100 2040855 http://www.medworm.com/index.php?rid=2040854&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103368 This article describes the current status, challenges, and future hopes with respect to molecular genetic testing in hemostasis and thrombosis from the perspective of experts from three countries: Brazil, Colombia, and Iran. These individuals have lived and practiced genetic testing in their countries and have also had the experience to work and/or interact with the developed world to enable an appreciation of the difference.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040854 Wed, 17 Dec 2008 13:33:16 +0100 2040854 http://www.medworm.com/index.php?rid=2040853&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103367 Semin Thromb Hemost 2008; 34: 562-568DOI: 10.1055/s-0028-1103367ABSTRACTImportant biochemical constituents of the fibrinolytic system include tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). In the current review, we aim to describe the genetic architecture of t-PA and PAI-1. Several genetic polymorphisms in the and gene have been found to be associated with t-PA and PAI-1 levels in different patient cohorts. However, these genetic variations explain only a minor part of the heritability of t-PA and PAI-1, suggesting that genes in other pathways may influence t-PA and PAI-1 levels, and that epistasis and gene-environment interactions may play an important role in determining plasma levels of t-PA and PAI-1. Several studies reported that interindividua... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040853 Wed, 17 Dec 2008 13:33:16 +0100 2040853 http://www.medworm.com/index.php?rid=2040852&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103366 Semin Thromb Hemost 2008; 34: 549-561DOI: 10.1055/s-0028-1103366ABSTRACTOver the past 20 years, the landscape with respect to evaluation of thrombophilia, the inherited or acquired tendency to develop venous thromboembolism, has changed dramatically. Increased knowledge regarding the contribution of genetic predisposition to thrombosis has raised several questions regarding screening, diagnosis, and management. In this review, we will examine these issues while providing an update on genetic testing for inherited thrombotic disorders.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040852 Wed, 17 Dec 2008 13:33:16 +0100 2040852 http://www.medworm.com/index.php?rid=2040851&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103365 Semin Thromb Hemost 2008; 34: 539-548DOI: 10.1055/s-0028-1103365ABSTRACTMolecular typing for platelet allelic polymorphisms was first made possible by discovery of the HPA-1a/1b single nucleotide polymorphism in 1989. Since then, six other biallelic human platelet antigen (HPA) systems have been determined and can be typed using genomic DNA. The introduction of polymerase chain reaction enabled development of several different assays including polymerase chain reaction–sequence-specific primer, melting curve analysis by LightCycler, and 5′-nuclease assays. More recently, multiplex polymerase chain reaction has allowed for the development of high-throughput assays for genotyping large numbers of patients and blood donors for not only platelet gene polymorphisms but also for thos... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040851 Wed, 17 Dec 2008 13:33:16 +0100 2040851 http://www.medworm.com/index.php?rid=2040850&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103364 Semin Thromb Hemost 2008; 34: 532-538DOI: 10.1055/s-0028-1103364ABSTRACTThe transcriptome is the mRNA pool found within a cell. Transcriptomic discovery approaches include microarray-based technologies as well as sequencing-based technologies. Transcriptomic experiments provide dynamic information about gene expression at the tissue level. The proteome is the pool of proteins expressed at a given time and circumstance. The word summarizes several technologies for visualization, quantitation, and identification of these proteins. Protein separation can be accomplished by two-dimensional electrophoresis, use of protein chips with an affinity matrix, or by a variety of advanced chromatographic methods. Mass spectrometry is used to identify the proteins in conjunction with protein sequence dat... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040850 Wed, 17 Dec 2008 13:33:16 +0100 2040850 http://www.medworm.com/index.php?rid=2040849&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103363 Semin Thromb Hemost 2008; 34: 520-531DOI: 10.1055/s-0028-1103363ABSTRACTType 2B von Willebrand disease (VWD) is a qualitative type of VWD with a unique feature among VWD types, resulting from an increased binding of von Willebrand factor (VWF) to its platelet receptor glycoprotein 1b-α (GP1BA). This heightened responsiveness takes place in vivo without endothelial injury or shear stress induction, typically resulting in loss of the hemostatically most active high-molecular-weight VWF multimers and leading to a bleeding diathesis. This process also typically leads to clearance of platelets and thus usually mild thrombocytopenia. At least this describes the classic representation of type 2B VWD (i.e., the typical picture we have come to know since the description/classification of this ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040849 Wed, 17 Dec 2008 13:33:16 +0100 2040849 http://www.medworm.com/index.php?rid=2040848&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103362 Semin Thromb Hemost 2008; 34: 509-519DOI: 10.1055/s-0028-1103362ABSTRACTWith the strides being made in the European, Canadian, and American prospective studies of von Willebrand disease (VWD) genotype and phenotype, genetics is increasingly playing a key role in the classification, understanding, and management of VWD. It is anticipated that as gene sequencing becomes easier and more commonplace and the relationship between genotype and clinical and laboratory phenotype becomes clearer, genetic analysis will assume an increasingly important role in diagnosis, prediction of clinical severity, response to hemostatic agents, and optimal individualized management. This is an evolving field, so the reader is urged to stay tuned as new information becomes available, as it will likely change how ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040848 Wed, 17 Dec 2008 13:33:16 +0100 2040848 http://www.medworm.com/index.php?rid=2040847&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103361 Semin Thromb Hemost 2008; 34: 502-508DOI: 10.1055/s-0028-1103361ABSTRACTvon Willebrand disease (VWD) is the most common inherited bleeding disorder in humans, but its diagnosis, using conventional clinical criteria and phenotypic hemostasis test results, can be problematic. The von Willebrand factor gene was cloned in the mid-1980s, and since that time, a significant amount of information has been gathered with respect to the molecular pathology responsible for this trait. This accumulated information, along with advances in genetic technology, has now made the integration of molecular genetic testing for VWD a feasible option in some instances. In this review, we have summarized the current state of knowledge concerning the genetic causation of the various forms of VWD. We have also provi... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040847 Wed, 17 Dec 2008 13:33:16 +0100 2040847 http://www.medworm.com/index.php?rid=2040846&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103360 This article describes recent advances in several aspects of genetic analysis and its interpretation and reporting. The intron 1 and 22 inversions responsible for 50% of severe hemophilia A cases can be sought using long and inverse polymerase chain reaction (PCR) techniques. Point mutations are analyzed in remaining patients by PCR amplification of the protein-coding region followed by either mutation screening to identify the mutated amplicon and subsequent DNA sequencing or by directly sequencing amplified DNA. Many technique modifications and sequence analysis software packages are available to reduce time and effort required to identify a mutation. Dosage analysis and gap PCR have been described to identify carriers of large deletions. Noninvasive prenatal fetal sex determination and ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040846 Wed, 17 Dec 2008 13:33:16 +0100 2040846 http://www.medworm.com/index.php?rid=2040845&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1103359 Semin Thromb Hemost 2008; 34: 485-489DOI: 10.1055/s-0028-1103359© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=2040845 Tue, 16 Dec 2008 03:00:54 +0100 2040845 http://www.medworm.com/index.php?rid=1915407&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086093 Semin Thromb Hemost 2008; 34: 128-129DOI: 10.1055/s-0028-1086093© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915407 Wed, 29 Oct 2008 15:11:32 +0100 1915407 http://www.medworm.com/index.php?rid=1915406&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086092 Semin Thromb Hemost 2008; 34: 119-127DOI: 10.1055/s-0028-1086092ABSTRACTAn unexpectedly high rate of adverse events and deaths were reported from November 2007 to April 2008 in patients exposed to heparin. Investigations on the quality of heparin revealed an oversulfated chondroitin sulfate (OSCS) contaminant in the heparin. Several reports on the chemical structure and limited biologic actions of OSCS have recently become available. However, no data are available on its anticoagulant and antiprotease effects. Moreover, its interaction with heparin, resulting in the modulation of heparin's anticoagulant activity, is not reported. The isolated contaminant from recalled batches of heparin and several semisynthetic OSCSs were profiled for their in vitro anticoagulant effects. The contaminant ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915406 Wed, 29 Oct 2008 15:11:32 +0100 1915406 http://www.medworm.com/index.php?rid=1915405&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086091 In this study, the anticoagulant bioequivalence of the generic and branded argatrobans were compared using whole blood, platelet-rich plasma, platelet-poor plasma, and antithrombin-deficient plasma using clot-based assays. In addition, biochemical systems related to hemostatic mechanisms that involve thrombin were employed, including thrombin generation, factor Xa generation, platelet activation, fibrinokinetics, and activation of thrombin activatable fibrinolytic inhibitor. Overall, the order of potency was gartban > slovastan > argatroban = argaron; however, the degree of potency differed by assay. Moreover, the inhibition of thrombin by each drug resulted in different mechanisms, as demonstrated in assays dependent on thrombin for enzymatic activation. Thes... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915405 Wed, 29 Oct 2008 15:11:32 +0100 1915405 http://www.medworm.com/index.php?rid=1915404&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086090 Semin Thromb Hemost 2008; 34: 103-107DOI: 10.1055/s-0028-1086090ABSTRACTA model of functional nephrectomy and hepatectomy in rats was used to compare the pharmacokinetic profile of the direct competitive thrombin inhibitor argatroban in rats with renal, hepatic, or hepatorenal failure and rats with normal hepatic and renal function. The pharmacokinetics of argatroban in rats after an intravenous bolus was described by an open two-compartment model with first-order elimination. This profile was not affected in nephrectomized rats, but hepatectomized rats showed a markedly increase in area under the curve values, distribution, and elimination half-life in comparison with untreated rats as expected for a drug eliminated primarily by the liver. Unexpectedly, blood levels of argatroban were low... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915404 Wed, 29 Oct 2008 15:11:32 +0100 1915404 http://www.medworm.com/index.php?rid=1915403&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086089 Semin Thromb Hemost 2008; 34: 097-102DOI: 10.1055/s-0028-1086089ABSTRACTThe direct thrombin inhibitors (DTIs) argatroban, lepirudin, and bivalirudin are used for the management of thrombosis in patients with heparin-induced thrombocytopenia (HIT). Based on the structure of argatroban, there may be additional pharmacological effects beyond thrombin inhibition, such as vasomodulation, anti-inflammatory, and cellular modulatory effects. Plasma samples collected from HIT patients treated with argatroban (n = 20), lepirudin (n = 15), or bivalirudin (n = 15) were profiled for markers of inflammation. Circulating levels of myeloperoxidase (MPO), CD-40 ligand (CD40L), and functional microparticles (thrombin generating) were higher in HIT patients versus controls... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915403 Wed, 29 Oct 2008 15:11:32 +0100 1915403 http://www.medworm.com/index.php?rid=1915402&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086088 This study suggests that argatroban, bivalirudin, and danaparoid have comparable potential to inhibit thrombin or Xa and the consequent coagulation, rendering the fibrin network permeable. The lack of influence on fibrin gel permeability by lepirudin at the “plasma-like” levels may contradict the antithrombotic effect observed in therapy, but the sharp dose–response curve shown at higher drug concentrations corresponds with reports of bleeding complications from lepirudin with overdosages.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915402 Wed, 29 Oct 2008 15:11:32 +0100 1915402 http://www.medworm.com/index.php?rid=1915401&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086087 This study reveals clear distinctions between the mechanisms of these two thrombin inhibitors.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915401 Wed, 29 Oct 2008 15:11:32 +0100 1915401 http://www.medworm.com/index.php?rid=1915400&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086086 Semin Thromb Hemost 2008; 34: 081-086DOI: 10.1055/s-0028-1086086ABSTRACTThe ecarin chromogenic assay (HaemoSys ECA; JenAffin GmbH, Jena, Germany) was developed for quantitative determination of direct thrombin inhibitors. As a further development of the ecarin clotting time (ECT), the ECA is based on the same principle of measurement: the activation of prothrombin by ecarin, a snake venom from . In the ECA, the prothrombin activation products meizothrombin and meizothrombin-des-F1 cleave a chromogenic substrate. The activity of meizothrombin/meizothrombin-des-F1 is inhibited in a concentration-dependent manner by direct thrombin inhibitors. The ECA-T is an assay for quantitative determination of active site directed synthetic thrombin inhibitors. For argatroban ECA-T, there is a very preci... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915400 Wed, 29 Oct 2008 15:11:32 +0100 1915400 http://www.medworm.com/index.php?rid=1915399&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086085 Semin Thromb Hemost 2008; 34: 075-080DOI: 10.1055/s-0028-1086085ABSTRACTThe direct thrombin inhibitor argatroban exhibits pharmacological properties that are distinctly different from those of other thrombin inhibitors. Within its clinically relevant dose range, argatroban shows linear pharmacokinetic behavior and concentrations that are well correlated with anticoagulant effects. The pharmacokinetic profile can be described by a two-compartment model with first-order elimination. Whereas argatroban does not require dosage modification in patients with renal dysfunction and has been demonstrated to be safe and well tolerated in hemodialysis, dosing precautions are recommended in hepatically impaired patients. The effects of high-dose or prevention therapy can be monitored by various coagul... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915399 Wed, 29 Oct 2008 15:11:32 +0100 1915399 http://www.medworm.com/index.php?rid=1915398&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086084 Semin Thromb Hemost 2008; 34: 062-074DOI: 10.1055/s-0028-1086084ABSTRACTConcomitant anticoagulant therapy is essential in patients undergoing percutaneous coronary interventions (PCI) to achieve prompt, early, complete, and sustained coronary artery recanalization. Heparin has been historically used in these procedures. Argatroban is a small-molecule, synthetic, reversible direct thrombin inhibitor. It has a predictable anticoagulant response and also the potential to inhibit clot-bound thrombin. The accessibility of argatroban to the active site of clot-bound thrombin is an advantage for the treatment of coronary occlusion. This is accomplished by virtue of the low molecular weight of argatroban (527 Da). Argatroban has been shown in clinical studies to be a safe and effective anticoagula... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915398 Wed, 29 Oct 2008 15:11:32 +0100 1915398 http://www.medworm.com/index.php?rid=1915397&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086083 Semin Thromb Hemost 2008; 34: 056-061DOI: 10.1055/s-0028-1086083ABSTRACTHemodialysis is indicated in uremic patients with endstage renal failure. Unfractionated heparin (heparin) is routinely used as the anticoagulant for hemodialysis, but heparin is contraindicated for dialysis of patients with antithrombin deficiency or heparin-induced thrombocytopenia (HIT). With heparin, these patients often encounter clotted dialyzers and extracorporeal circuits that lead to discontinuation of dialysis. As one alternative to heparin, argatroban (a synthetic thrombin inhibitor mainly eliminated via the hepatobiliary tract) is indicated. In uremic patients with antithrombin deficiency, the alternative use of argatroban has made it feasible to carry out hemodialysis. In patients with HIT undergoing dialy... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915397 Wed, 29 Oct 2008 15:11:32 +0100 1915397 http://www.medworm.com/index.php?rid=1915396&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086082 This article focuses on the argatroban dosing protocols in patients after cardiac surgery and ICU patients with and without RRT.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915396 Wed, 29 Oct 2008 15:11:32 +0100 1915396 http://www.medworm.com/index.php?rid=1915395&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086081 Semin Thromb Hemost 2008; 34: 048-051DOI: 10.1055/s-0028-1086081ABSTRACTThe main features of heparin-induced thrombocytopenia (HIT) are massive coagulation activation despite heparin anticoagulation and a drop in platelet count. A large proportion of patients with HIT develop thromboembolic complications if not treated with a nonheparin anticoagulant such as argatroban, danaparoid, or lepirudin. Whereas both lepirudin and danaparoid require dose adjustments or are contraindicated in patients with impaired renal function, argatroban can be used at normal therapeutic doses in these patients. Dose adjustments of argatroban are only necessary in patients with compromised liver function. Due to its short half-life, argatroban is an ideal anticoagulant for the perioperative phase. Argatroban typ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915395 Wed, 29 Oct 2008 15:11:32 +0100 1915395 http://www.medworm.com/index.php?rid=1915394&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086080 We report on three specific cases anticoagulated with argatroban for CPB showing the difficulty of anticoagulation management. We review several retrospective studies and a multicenter, prospective cohort study that suggest a lower incidence of HIT in Japan than what is diagnosed in Western countries. This may be due to ethnic factors and/or different clinical practices. We conducted a multicenter, nonrandomized, open-label trial showing the efficacy and safety of argatroban when carefully dosed. From this study we describe a Japanese strategy to diagnose and treat HIT that may be of value elsewhere.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915394 Wed, 29 Oct 2008 15:11:32 +0100 1915394 http://www.medworm.com/index.php?rid=1915393&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086079 Semin Thromb Hemost 2008; 34: 027-036DOI: 10.1055/s-0028-1086079ABSTRACTAlthough the prevalence of heparin-induced thrombocytopenia (HIT) has decreased these last years in France with the widespread use of low molecular weight heparins, HIT remains an important severe prothrombotic disease that needs to be diagnosed and treated adequately. HIT is caused by IgG antibodies that bind to modified platelet factor 4 and induce platelet and monocyte activation with increased thrombin generation. Venous and arterial thromboses are therefore frequent in HIT, explaining why substituting heparin with a potent alternative anticoagulant such as danaparoid sodium, lepirudin, or argatroban is necessary in every affected patient. However, the management of these drugs is difficult, and the diagnosis of HI... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915393 Wed, 29 Oct 2008 15:11:32 +0100 1915393 http://www.medworm.com/index.php?rid=1915392&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086078 Semin Thromb Hemost 2008; 34: 018-026DOI: 10.1055/s-0028-1086078ABSTRACTHeparin-induced thrombocytopenia (HIT), sometimes complicated by the occurrence of thrombosis (HITT), is a rare but severe complication of heparin therapy (both unfractionated and low molecular weight heparin). It is induced by the generation of antibodies targeted to complexes of platelet factor (PF) 4 and heparin (H), mainly IgG isotypes with the highest avidity. Laboratory studies and clinical surveys help elucidate the mechanisms of HIT/HITT. The presence of stoichiometric complexes of H-PF4 is probably the immunogenic stimulus that induces the generation of antibodies, via a T-cell response. In pathologies, where a large extent of platelet activation occurs, especially at the vicinity of pathological sites, large ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915392 Wed, 29 Oct 2008 15:11:32 +0100 1915392 http://www.medworm.com/index.php?rid=1915391&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086077 This article reviews the present state of direct thrombin inhibitors, including compounds that are administered parenterally (lepirudin, bivalirudin, argatroban, napsagatran, and Melagatran [AstraZeneca, Mölndal, Sweden]) and those that can be given orally (ximelagatran and dabigatran etexilate). Lepirudin and argatroban (in the United States but not in all European countries) are licensed for treatment of heparin-induced thrombocytopenia (HIT) (argatroban also for prophylaxis), whereas bivalirudin is approved as an alternative to heparin in patients undergoing percutaneous coronary interventions (PCI) and argatroban for PCI in patients with HIT. Napsagatran development has ceased, and ximelagatran has not been granted approval by the U.S. Food and Drug Administration and was withdrawn fr... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915391 Wed, 29 Oct 2008 15:11:32 +0100 1915391 http://www.medworm.com/index.php?rid=1915390&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086076 Semin Thromb Hemost 2008; 34: 007-011DOI: 10.1055/s-0028-1086076ABSTRACTArgatroban, the world's first direct thrombin inhibitor, developed by Shosuke Okamoto et al, is based on three development concepts: “exceeding global standards,” “avoiding current trends in research,” and “exploring drugs.” Okamoto sought compounds that strongly and selectively inhibited thrombin throughout his research on thrombin inhibitors. Compounds that selectively inhibit a specific enzyme can be used as a powerful tool to elucidate the physiological and pathological roles of that enzyme. As of January 2008, argatroban has been approved in 12 countries including Japan and used in several patients with chronic arterial thrombosis, acute cerebral thrombosis, and heparin-induced ... Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915390 Wed, 29 Oct 2008 15:11:32 +0100 1915390 http://www.medworm.com/index.php?rid=1915389&cid=s_36599_19_f&fid=36599&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1086075 Semin Thromb Hemost 2008; 34: 005-006DOI: 10.1055/s-0028-1086075© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Thrombosis and Hemostasis) Seminars in Thrombosis and Hemostasis journals http://www.medworm.com/rss/comments.php?id=1915389 Wed, 29 Oct 2008 15:11:32 +0100 1915389