MedWorm: Hematology

Long-term plasma exchange for severe refractory hypertriglyceridemia: A decade of experience demonstrates safety and efficacy

Journal of Clinical Apheresis — Fri, 20 Nov 2009 00:00:00 +0100

Hypertriglyceridemia (hyperTG) is a common form of dyslipidemia and is frequently associated with premature coronary disease, and when severe, recurrent events of pancreatitis may occur. The management of hyperTG is generally medical (life style modification, medications). Plasma exchange (PE) has been reported to be useful in emergency situations particularly when acute pancreatitis results from extreme hyperTG. To our knowledge, there is only one report on long-term use of PE for hyperTG. We here report our results of long-term treatment of hyperTG in 6 patients with Frederickson Type V hyperlipidemia who had recurrent attacks of pancreatitis due to hyperTG refractory to medical therapy. PE was performed from one to eight times a month, mostly using a Cobe Spectra apparatus. In total, ou...

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Breast Cancer Screening: New Fuel for an Old War of Words and Data

MedPage Today Hematology/Oncology — Thu, 19 Nov 2009 22:44:24 +0100

A controversy that has alternately simmered and boiled for more than 40 years reached a flash point this week when the U.S. Preventive Services Task Force published recommendations for breast cancer screening with mammography. (Source: MedPage Today Hematology/Oncology)

Response: MHC class I chain-related gene A (MICA) in unrelated donor transplantation

Blood — Thu, 19 Nov 2009 17:02:20 +0100

(Source: Blood)

Limited role of MHC class I chain-related gene A (MICA) typing in assessing graft-versus-host disease risk after fully human leukocyte antigen-matched unrelated donor transplantation

Blood — Thu, 19 Nov 2009 17:02:20 +0100

(Source: Blood)

Mutation of the H-bond acceptor S119 in the ADAMTS13 metalloprotease domain reduces secretion and substrate turnover in a patient with congenital thrombotic thrombocytopenic purpura

Blood — Thu, 19 Nov 2009 17:02:20 +0100

In this study the functional and structural role of a recently identified ADAMTS13 metalloprotease domain mutation S119F was investigated. Secretion from heterologous cells was hampered but not completely eliminated. Secreted S119F was active toward multimeric VWF and FRETS-VWF73 but with abnormal kinetics, having a significantly reduced overall catalytic rate (kcat; 0.88 ± 0.04 s–1 vs 2.78 ± 0.11 s–1) and slightly smaller Michaelis constant (KM; 1.4 ± 0.2µM vs 2.3 ± 0.3µM). A computational model of the metalloprotease domain demonstrates both steric and polar interaction effects caused by S119F. Interestingly, mutant S119A has properties similar to S119F (kcat = 0.82 ± 0.03 s–1 and KM = 1.1 ± 0.1µM), allowing to...

A role for thrombin in the initiation of the immune response to therapeutic factor VIII

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Administration of human factor VIII (FVIII) to FVIII knockout hemophilia mice is a useful small animal model to study the physiologic response in patients iatrogenically immunized to this therapeutic protein. These mice manifest a robust, T cell–dependent, antibody response to exogenous FVIII treatment, even when encountered through traditionally tolerogenic routes. Thus, FVIII given via these routes elicits both T- and B-cell responses, whereas a control, foreign protein, such as ovalbumin (OVA), is poorly immunogenic. When FVIII is heat inactivated, it loses function and much of its immunogenicity. This suggests that FVIII's immunogenicity is principally tied to its function and not its structure. If mice are treated with the anticoagulant warfarin, which depletes other coagulation...

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Platelet protein disulfide isomerase is localized in the dense tubular system and does not become surface expressed after activation

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Evidence is accumulating that circulating tissue factor (TF) contributes to the initiation of coagulation and the formation of fibrin. The majority of circulating TF is cryptic, and it has been suggested that close vicinity with anionic phospholipids on the cell surface increases the active conformation of TF. Two recent papers have shown that encryption of TF and initiation of coagulation are facilitated by the enzyme protein disulfide isomerase (PDI), possibly on the surface of activated platelets or endothelial cells. In this brief report, we demonstrate that the majority of PDI in platelets is intracellular where it is exclusively located in the dense tubular system. On activation, PDI remains confined to the intracellular stores of the dense tubular system and is neither released nor ...

Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP

Blood — Thu, 19 Nov 2009 17:02:20 +0100

The role of the Wiskott-Aldrich syndrome protein (WASp) in platelet function is unclear because platelets that lack WASp function normally. WASp constitutively associates with WASp-interacting protein (WIP) in resting and activated platelets. The role of WIP in platelet function was investigated using mice that lack WIP or WASp. WIP knockout (KO) platelets lack WASp and thus are double deficient. WIP KO mice have a thrombocytopenia, similar to WASp KO mice, resulting in part from enhanced platelet clearance. Most WIP KO, but not WASp KO, mice evolved platelet-associated immunoglobulins (Ig) of the IgA class, which normalize their platelet survival but diminish their glycoprotein VI (GPVI) responses. Protein tyrosine phosphorylation, including that of phospholipase C-2, and calcium mobiliza...

The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Neutrophils play a vital role in the immune defense, which is evident by the severity of neutropenia causing life-threatening infections. Granulocyte macrophage-colony stimulating factor (GM-CSF) controls homeostatic and emergency development of granulocytes. However, little is known about the contribution of the downstream mediating transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A/B). To elucidate the function of this pathway, we generated mice with complete deletion of both Stat5a/b genes in hematopoietic cells. In homeostasis, peripheral neutrophils were markedly decreased in these animals. Moreover, during emergency situations, such as myelosuppression, Stat5a/b-mutant mice failed to produce enhanced levels of neutrophils and were unable to respo...

Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy

Blood — Thu, 19 Nov 2009 17:02:20 +0100

An important hallmark of cancer progression is the ability of tumor cells to evade immune recognition. Understanding the relationship between neoplastic cells and the immune microenvironment should facilitate the design of improved immunotherapies. Here we identify impaired T-cell immunologic synapse formation as an active immunosuppressive mechanism in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). We found a significant reduction in formation of the F-actin immune synapse in tumor-infiltrating T cells (P < .01) from lymphoma patients compared with age-matched healthy donor cells. Peripheral blood T cells exhibited this defect only in patients with leukemic-phase disease. Moreover, we demonstrate that this T-cell defect is induced after short-term tumor cell contac...

TAPP2 links phosphoinositide 3-kinase signaling to B-cell adhesion through interaction with the cytoskeletal protein utrophin: expression of a novel cell adhesion-promoting complex in B-cell leukemia

Blood — Thu, 19 Nov 2009 17:02:20 +0100

We examined whether TAPP can regulate cell adhesion, a known function of utrophin/syntrophin in other cell types. Expression of membrane-targeted TAPP2 enhanced B-cell adhesion to fibronectin and laminin, whereas PH domain–mutant TAPP2 inhibited adhesion. siRNA knockdown of TAPP2 or utrophin, or treatment with PI3K inhibitors, significantly inhibited adhesion. These findings identify TAPP2 as a novel link between PI3K signaling and the cytoskeleton with potential relevance for leukemia progression. (Source: Blood)

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Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated (M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine. Of 58 HCLs, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53 of 58 patients (91%), whereas treatment failures were observed in 5 of 58 patients (9%). Failures were associated significantly with UM-IGHV (5 of 5 failures vs 1 of 53 beneficial responses had UM-IGHV, P < .001), leukocytosis (3 of 5 vs 3 of 53, P = .006), and bulky spl...

VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Hairy cell leukemia variant (HCLv) presents with high disease burden, lack of typical antigens like CD25, and poor response to standard treatments like cladribine. Occasionally, patients with classic HCL respond poorly. Clinical and molecular features of HCL and HCLv has not been compared. Rearrangements expressing immunoglobulin VH chain were sequenced, including 22 from 20 patients with HCLv and 63 from 62 patients with classic HCL. Most patients were seeking relapsed/refractory trials, representing a poor-prognosis population. VH4-34, a gene commonly used in autoimmune disorders, was observed in 8 (40%) HCLv and 6 (10%) classic (P = .004) HCL patients. Compared with 71 VH4-34– rearrangements, 14 VH4-34+ rearrangements were more frequently (P < .001) unmutated, defined as greate...

High TCL1 levels are a marker of B-cell receptor pathway responsiveness and adverse outcome in chronic lymphocytic leukemia

Blood — Thu, 19 Nov 2009 17:02:20 +0100

Although activation of the B-cell receptor (BCR) signaling pathway is implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), its clinical impact and the molecular correlates of such response are not clearly defined. T-cell leukemia 1 (TCL1), the AKT modulator and proto-oncogene, is differentially expressed in CLL and linked to its pathogenesis based on CD5+ B-cell expansions arising in TCL1-transgenic mice. We studied here the association of TCL1 levels and its intracellular dynamics with the in vitro responses to BCR stimulation in 70 CLL cases. The growth kinetics after BCR engagement correlated strongly with the degree and timing of induced AKT phospho-activation. This signaling intensity was best predicted by TCL1 levels and the kinetics of TCL1-AKT corecruitment to BCR ...

Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes

Blood — Thu, 19 Nov 2009 17:02:19 +0100

This study identifies the E-cadherin/catenin complex as a discriminative, partly polyamine-regulated feature of IL-4/IL-13–exposed alternatively activated macrophages that contributes to homotypic and heterotypic cellular interactions. (Source: Blood)

The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish

Blood — Thu, 19 Nov 2009 17:02:19 +0100

The nuclear protein FOG-1 binds transcription factor GATA-1 to facilitate erythroid and megakaryocytic maturation. However, little is known about the function of FOG-1 during myeloid and lymphoid development or how FOG-1 expression is regulated in any tissue. We used in situ hybridization, gain- and loss-of-function studies in zebrafish to address these problems. Zebrafish FOG-1 is expressed in early hematopoietic cells, as well as heart, viscera, and paraspinal neurons, suggesting that it has multifaceted functions in organogenesis. We found that FOG-1 is dispensable for endoderm specification but is required for endoderm patterning affecting the expression of late-stage T-cell markers, independent of GATA-1. The suppression of FOG-1, in the presence of normal GATA-1 levels, induces sever...

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Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling

Blood — Thu, 19 Nov 2009 17:02:19 +0100

The first adult-repopulating hematopoietic stem cells (HSCs) are detected starting at day 10.5 of gestation in the aorta-gonads-mesonephros (AGM) region of the mouse embryo. Despite the importance of the AGM in initiating HSC production, very little is currently known about the regulators that control HSC emergence in this region. We have therefore further defined the location of HSCs in the AGM and incorporated this information into a spatial and temporal comparative gene expression analysis of the AGM. The comparisons included gene expression profiling (1) in the newly identified HSC-containing region compared with the region devoid of HSCs, (2) before and after HSC emergence in the AGM microenvironment, and (3) on populations enriched for HSCs and their putative precursors. Two genes fo...

Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease

Blood — Thu, 19 Nov 2009 17:02:19 +0100

In conclusion, increase in hemoglobin F in sickle cell disease may be associated with relatively lower tissue oxygen delivery as reflected in higher erythropoietin concentration. Greater levels of erythropoietin or hemoglobin F were independently associated with higher tricuspid regurgitation velocity after adjustment for degree of hemolysis, suggesting an independent relationship of hypoxia with higher systolic pulmonary artery pressure. The hemolysis-lowering and hemoglobin F–augmenting effects of hydroxyurea may exert countervailing influences on pulmonary blood pressure in sickle cell disease. (Source: Blood)

Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury

Blood — Thu, 19 Nov 2009 17:02:19 +0100

Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng...

How I treat postthrombotic syndrome

Blood — Thu, 19 Nov 2009 17:02:19 +0100

Postthrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT) that reduces quality of life and has important socioeconomic consequences. More than one-third of patients with DVT will develop PTS, and 5% to 10% of patients will develop severe PTS, which may manifest as venous ulceration. The principal risk factors for PTS are persistent leg symptoms 1 month after the acute episode of DVT, extensive DVT, recurrent ipsilateral DVT, obesity, and older age. Daily use of elastic compression stockings (ECSs) for 2 years after proximal DVT appears to reduce the risk of PTS; however, there is uncertainty about optimal duration of use and compression strength of ECSs and the magnitude of their effect. The cornerstone of managing PTS is compression therapy, primarily using E...

Mechanisms underlying neutrophil-mediated monocyte recruitment

Blood — Thu, 19 Nov 2009 17:02:19 +0100

Extravasation of polymorphonuclear leukocytes (PMNs) to the site of inflammation precedes a second wave of emigrating monocytes. That these events are causally connected has been established a long time ago. However, we are now just beginning to understand the molecular mechanisms underlying this cellular switch, which has become even more complex considering the emergence of monocyte subsets, which are affected differently by signals generated from PMNs. PMN granule proteins induce adhesion as well as emigration of inflammatory monocytes to the site of inflammation involving β2-integrins and formyl-peptide receptors. Furthermore, modification of the chemokine network by PMNs and their granule proteins creates a milieu favoring extravasation of inflammatory monocytes. Finally, emigrat...

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Cracking the platelet WIP

Blood — Thu, 19 Nov 2009 17:02:19 +0100

(Source: Blood)

IG genes and hairy cell leukemia

Blood — Thu, 19 Nov 2009 17:02:19 +0100

(Source: Blood)

Macrophage fusion cuisine

Blood — Thu, 19 Nov 2009 17:02:19 +0100

(Source: Blood)

Millennium Initiates First Clinical Trial With The First Oral Proteasome Inhibitor

Lymphoma / Leukemia News From Medical News Today — Thu, 19 Nov 2009 14:00:00 +0100

Millennium: The Takeda Oncology Company announced it has further expanded its protein homeostasis program with the initiation of a Phase I clinical trial for an oral formulation of MLN9708, the Company's second-generation proteasome inhibitor. An intravenous formulation of MLN9708 entered clinical trials in March. MLN9708 is the third molecule Millennium has developed from its innovative research in protein homeostasis. (Source: Lymphoma / Leukemia News From Medical News Today)

Clinical and Applied Thrombosis/Hemostasis: Instructions for Authors

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

(Source: Clinical and Applied Thrombosis/Hemostasis)

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A Platelet Defect Modulates Bleeding in Mild Hemophilia: The Tale of 2 Brothers

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

(Source: Clinical and Applied Thrombosis/Hemostasis)

Book Review: New Therapeutic Agents in Thrombosis and Thrombolysis. Jane E. Freedman and Joseph Loscalzo, Editors. 3rd ed. New York, London: Informa Healthcare, 2009. 690 pp. $299.95. USBM 13 1420069235. Illustrated

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

(Source: Clinical and Applied Thrombosis/Hemostasis)

Book Review: Coagulation in Cancer. David Green and Hau C. Kwaan, Editors. New York, NY: Springer Science + Business Media LCC, 2009. 339 pp. Price $129.00

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

(Source: Clinical and Applied Thrombosis/Hemostasis)

A Woman With Rectal Sinus and Left Transversal Sinus Thrombosis After Ovarian Stimulation: Case Report

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

We describe a case of dual cerebral vein thrombosis in a woman with prothrombin mutation homozygosity and ovarian hyperstimulation syndrome. (Source: Clinical and Applied Thrombosis/Hemostasis)

Acute Massive Pulmonary Embolism With Hemodynamic Compromise Treated Successfully With Thrombolytic Therapy Selcuk

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

A 78 year-old woman presented with a history of 15 days of dyspnea and tachypnea at rest. A distended right ventricle with free-wall hypokinesis and displacement of the interventricular septum toward the left ventricle were shown on echocardiography. The patient suddenly arrested. She underwent cardiac catheterization and selective pulmonary angiography for suspected pulmonary embolism while undergoing cardiopulmonary resuscitation. With the diagnosis of pulmonary embolism confirmed, recombinant tissue plasminogen activator was given immediately in the catheterization room. This case shows how pulmonary embolism can be diagnosed with pulmonary angiography during cardiopulmonary resuscitation and the life-saving result from rapid thrombolysis with recombinant tissue plasminogen activator. (...

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Diffuse Cerebral Infarct Associated With Factor V Leiden and Prothrombin 20210A Mutations in a Patient With Tetralogy of Fallot

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

A 2-year-old girl with tetralogy of Fallot presented with diffuse cranial infarct after cardiac angiography. Heterozygosity for factor V Leiden and prothrombin 20210A mutations were detected. The authors suggest that if thrombosis develops in patients with congenital heart disease, genetic risk factors should be evaluated. (Source: Clinical and Applied Thrombosis/Hemostasis)

Single Nucleotide Polymorphisms That Affect Homocysteine Levels in Turkish Population

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

In this study, single nucleotide polymorphisms (SNPs) involved in homocysteine metabolism such as CT replacement in the 677th nucleotide in 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme; 68-bp insertion in the 844th nucleotide of cystathionine β-synthase (CBS) enzyme; 6-bp insertion/deletion in the region of 3'UTR in thymidylate synthase (TYMS) enzyme and 19-bp deletion in dihydrofolate reductase (DHFR) enzyme were investigated. The effects of these mutations on homocysteine levels were studied. As a result; we found that TT genotype of MTHFR 677 CT is an influencing factor on homocysteine levels in Turkish population. Furthermore, there seems to be another MTHFR 677 TT haplotype, which does not have an effect on homocysteine levels .Our data revealed that other SNPs did not...

Oxidative Stress and Total Antioxidant Capacity in Diabetic and Nondiabetic Acute Ischemic Stroke Patients

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Free radical formation is the pivotal mechanism of neuronal injury of ischemic and reperfused brain tissue. In healthy individuals, antioxidant activity counterbalances free radical production, but in the case of ischemia, the balance between reactive oxygen species and antioxidant activity is shifted toward free radicals, causing oxidative stress. The aim of this study is to assess total antioxidant capacity (TAC) and oxidative stress in diabetic and nondiabetic acute stroke patients with 2 different stroke subtypes: large and small vessel disease stroke. Sixty-five acute ischemic stroke patients (29 diabetic and 36 nondiabetic) and 20 age-matched healthy control subjects were recruited in the study. Plasma TAC and nitric oxide (NO) metabolite levels (nitrite and nitrate) were measured by...

Effects of rhG-CSF Plus Dexamethasone on Hemostatic Parameters in Healthy Granulocyte Donors: Role of u-PA and Nitric Oxide

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Granulocyte colony-stimulating factor (G-CSF) is widely used to reduce the risk of infection resulting from neutropenias and to mobilize and collect CD34+ hematopoetic progenitor cells (HPCs) for autologous and allogenic transplantation. The safety of recombinant human G-CSF (rhG-CSF) administration in healthy donors has been investigated in several studies. However, there are limited cumulative data about the effects of rhG-CSF on hemostasis. Hemostatic parameters, including urokinase-type plasminogen activator antigen (u-PA:Ag) and nitric oxide in 17 healthy granulocyte apheresis donors who donated for neutropenic patients were evaluated. rhG-CSF (single dose, 10 µg/kg subcutaneously) and dexamethasone (8 mg, single dose oral) were given to donors 12 hours before granulocyte aphere...

Relative Purity of Different Bovine Thrombin Preparations

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

The aim of this study was to compare the relative purity of bovine crude thrombin and its purified forms, namely, thrombin 4A and thrombin 4B (the products of King Pharma, Middleton, Wisconsin) by virtue of the detection of bovine prothrombin-related antigens in these preparations. Bovine prothrombin was administered intravenously to 3 individual rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic method. Blood was drawn from each rabbit on days 30, 50, 105, 137, and 165, and the pooled antisera from 3 rabbits were purified to isolate immunoglobulin G (IgG) using protein G affinity columns. Using Western blotting method, serially diluted bovine crude thrombin, thrombin 4A, and 4B preparations were probed using the prothrombin IgGs obtained from each time point to explore...

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Venous Thromboembolism in Patients Hospitalized With Thyroid Dysfunction

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

In conclusion, an increased risk of PE, DVT, and VTE was shown in patients with hypothyroidism but not hyperthyroidism. Antithrombotic prophylaxis in patients with severe hypothyroidism, however, should be viewed with caution because of a possible hyperfibrinolytic state in such patients. (Source: Clinical and Applied Thrombosis/Hemostasis)

D-Dimers, Thrombin--Antithrombin Complexes, and Risk Factors for Thromboembolism in Hospitalized Patient

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Conclusions (a) this study is the first to describe the variations of hypercoagulability markers according to a systematic screening of RFs for VTE in inpatients without suspicion of acute VTE, (b) TAT appeared as a less relevant marker of hypercoagulability than D-dimers in internal medicine inpatients, (d) the chronological classification of RFs identified clearly groups at risk for the prethrombotic state, and (d) an increased hypercoagulability state was demonstrated in patients with an association between a recent immobility and increased inflammatory markers. (Source: Clinical and Applied Thrombosis/Hemostasis)

The Impact of Prothrombotic Mutations on Factor Consumption in Adult Patients with Severe Hemophilia

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

About 10% of patients with severe hemophilia exhibit a milder clinical phenotype with less frequent bleeds. Among many other factors, coinheritance of prothrombotic mutations have been proposed to act as modulators of clinical severity in severe hemophilia. We conducted a study to evaluate the impact of 3 prothrombotic mutations (factor V Leiden, factor II, and methylenetetrahydrofolate reductase mutations) on clinical phenotype of patients with severe hemophilia in our institution. For this purpose we compared the average annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. A total of 38 hemophilia A and B patients with factor levels less than 1 were recruited between October 2006 and October 2007. Prothrombotic mutations were detected in veno...

Utility of the PFA-100 Instrument and the Novel Multiplate Analyzer for the Assessment of Aspirin and Clopidogrel Effects on Platelet Function in Patients With Cardiovascular Disease

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

This study evaluated the utility of the PFA-100 and the Multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Platelet function was determined with the PFA-100 using collagen+epinephrine (CEPI) and collagen+adenosine-5’-diphosphate (CADP) cartridges, and with whole blood impedance aggregometry using the Multiplate ASPI and ADP+PG tests (aggregation triggered with arachidonic acid and ADP+ prostaglandin E1, respectively). Four study groups were identified from the 154 patients enrolled: patients without antiplatelet therapy, patients with 100 mg aspirin daily but without clopidogrel treatment, patients with 75 mg clopidogrel daily but without aspirin treatment, and patients with both 100 mg aspirin daily...

European Community and US-FDA Approval of Recombinant Human Antithrombin Produced in Genetically Altered Goats

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Thrombin and factor Xa play a central role in thrombogenesis in both medical and surgical patients. Antithrombin (AT) is the key inhibitor, which controls the action of these enzymes in hypercoagulable states. The AT concentrates prepared from human blood have been used to treat patients with thrombotic disorders and heparin resistance. The AT concentrates are prepared from pooled human plasma and beside limited supply, suffer from viral and other biological contaminants. The availability of recombinant human AT (rhAT) obtained from genetically engineered goats provide a biologically equivalent product that can be used in practically all indications where human AT is indicated including heparin resistance. Moreover, because of its high affinity to heparin and related drugs, recombinant AT ...

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Use of Heparin in Women With Early and Late Miscarriages With and Without Thrombophilia

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Conclusions: Our data support the notion that LMWH is efficacious in patients with recurrent abortions and thrombophilia. We demonstrated the same effect of LMWH in women with unexplained abortions without thrombophilia. The potential mechanism of action of LMWH in early and late abortions warrants further study. (Source: Clinical and Applied Thrombosis/Hemostasis)

Effect of Recombinant Activated Factor VII in Critical Bleeding: Clinical Experience of a Single Center

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Recombinant activated factor VII (rFVIIa) has been successfully used ‘‘off-label’’ in patients with refractory life-threatening hemorrhage. Intravenous rFVIIa was given to 31 patients unresponsive to standard therapy with blood products and surgical reexploration, who were bleeding due to trauma, surgery, organ transplantation, liver cirrhosis, ruptured uterus. We recorded their coagulation and hematologic profiles, acid-base balance, blood loss, number of red blood cells (RBC), plasma and platelet transfusions, complications, and survival. rFVIIa (mean dose 132.2 ± 56.3 µg/kg) effectively contained the hemorrhage in 28/31 (90.3%) cases, with a mean reduction in blood loss from 12.4 ± 10.2 to 2.7 ± 2.2 L (P < .0001). The need for RBC, p...

Unexplained Discrepancies in the Activity--Antigen Ratio in Congenital FX Deficiencies With Defects in the Catalytic Domain

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Studies on molecular biology have considerably enhanced our understanding of congenital coagulation disorders but have failed so far to supply tools for an adequate classification of defects. In fact, mutations in the same domain may give rise to different phenotypes. Conversely, mutations in different domains, controlled by different exons, may cause similar patterns. The 37 kindreds with congenital factor X (FX) deficiency, known to have a defect in the catalytic domain, have been evaluated in an attempt to investigate the genotype—phenotype relation. Discrepant results were obtained because about half kindreds showed a type I pattern, namely a concomitant decrease in FX activity and antigen. The other half showed a type II pattern, namely a decrease in FX activity with a normal or...

Rivaroxaban in Orthopedic Surgery -- A Change of Paradigm?

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Two selective, orally available anticoagulant agents, although with different targets in the coagulation cascade, have recently been approved in many countries on the indication of prophylaxis against venous thromboembolism (VTE) after major joint arthroplasty. This review discusses mainly the antifactor Xa drug, rivaroxaban, with a focus on the orthopedic trials. Pharmacokinetic characteristics and other clinical development programs with rivaroxaban are briefly reviewed. Although the aim of this article is not to review the direct thrombin inhibitor, dabigatran etexilate, some comparisons are made. For clinical results, these are obviously indirect and conclusions must be drawn with caution until head-to-head comparisons are performed. Whether the introduction of rivaroxaban is a change ...

Anticoagulant Therapy for Acute Venous Thromboembolism: What We Think We Know and What the Data Show for the Timing of Recurrent Events

Clinical and Applied Thrombosis/Hemostasis — Thu, 19 Nov 2009 05:33:27 +0100

Although heparin is administered to prevent early recurrences of venous thromboembolism (VTE) by preventing new thrombi, allowing old thrombi to attach to venous walls, and covering warfarin until it is therapeutic, heparin largely prevents late recurrences of VTE (after 5 days). The dreaded early occurrence of pulmonary embolism (PE) (on or before day 5) while waiting for the vitamin K antagonist to become antithrombotic did not occur among patients with deep venous thrombosis (DVT), who received acencoumarol alone. Fewer total recurrences resulted if a therapeutic level of heparin was reached within the first 24 hours of treatment of DVT. Fewer total recurrences also resulted if heparin was consistently maintained at therapeutic levels. A recurrent VTE within 5 days, however, occurred in...

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Neuropathy and Nutritional Supplements Survey

International Myeloma Foundation — Thu, 19 Nov 2009 05:00:00 +0100

Drs. Brian Durie and Paul Richardson are conducting a survey of myeloma patients to try and learn more about experience with neuropathy and nutritional supplements. If you would like to help by participating in the survey, click the More button. All responses are anonyomous. No personal identifying information is being collected. Your help would very much be appreciated. Many thanks! (Source: International Myeloma Foundation)

Age-related plasma reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4.

International Journal of Laboratory Hematology — Thu, 19 Nov 2009 04:32:08 +0100

This study was conducted to establish age-related reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4 (PF4)--and to determine if the quantitative values of these proteins may contribute to the reported age-dependent effect of unfractionated heparin (UFH). Plasma samples were obtained from healthy children aged between 1 month and 16 years and from healthy adult volunteers. Two commercial kits were used to measure plasma vitronectin and PF4 levels. Results were reported as mean and boundaries including 95% of the population. Plasma vitronectin levels for children aged 1-5 years were significantly higher compared with adults. Plasma PF4 levels for infants <1 year of age were significantly lower compared with adults. The differences between reference values...

Evaluation of mean platelet volume in the differential diagnosis of thrombocytopenia.

International Journal of Laboratory Hematology — Thu, 19 Nov 2009 04:32:05 +0100

Authors: Ntaios G, Papadopoulos A, Chatzinikolaou A, Girtovitis F, Kaiafa G, Savopoulos C, Hatzitolios A PMID: 19909383 [PubMed - in process] (Source: International Journal of Laboratory Hematology)

Immunoadsorption apheresis and immunosuppressive drug therapy in the treatment of complicated HCV-related cryoglobulinemia

Journal of Clinical Apheresis — Thu, 19 Nov 2009 00:00:00 +0100

The immunosuppressive drug therapy (IDT) is not always effective to avoid the development of complications in hepatitis C virus-related cryoglobulinemia (HCV-Cr). Removal of cryoglobulins by therapeutic plasmapheresis is currently accepted. In this randomized, parallel group study, 17 male and female patients aged 43-79 years, with complicated HCV-Cr, were submitted for 12 weeks (initial immunosuppressive therapy) to IDT ([alpha]-interferon, pegylated-interferon [alpha]-2a, cyclophosphamide, methylprednisolone, prednisone, cyclosporine, ribavirin, and melphalan). Then, they were randomly assigned to two parallel groups: A # 9 patients treated by immunoadsorption apheresis (Selesorb®) (IA) plus IDT, and B # 8 patients submitted to IDT only, for further 12 weeks. # 187 IA aphereses were per...

Different inflammatory responses induced by three LDL-lowering apheresis columns

Journal of Clinical Apheresis — Thu, 19 Nov 2009 00:00:00 +0100

In conclusion, three LDL-apheresis devices with equal cholesterol-lowering effect differed significantly with respect to the inflammatory response. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. (Source: Journal of Clinical Apheresis)

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Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura

British Journal of Haematology — Thu, 19 Nov 2009 00:00:00 +0100

We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) ( (Source: British Journal of Haematology)

The serological screening of deceased tissue donors within the English Blood Service for infectious agents – a review of current outcomes and a more effective strategy for the future

Vox Sanguinis — Thu, 19 Nov 2009 00:00:00 +0100

Conclusion Overall, the NHSBT screening programme for infectious agents in deceased tissue donors is very effective with a relatively low overall loss of donors because of non-specific reactivity. However, unnecessary loss of tissue products is not acceptable, and although this programme compares favourably with the outcomes of other such programmes, the confirmatory results obtained demonstrate both the need and the potential for improving the outcomes. This is particularly important as one donor may donate more than one product, and can be achieved very easily with a change to the screening algorithm followed, using the confirmatory data obtained to support and validate this change.Contents Summary Critical analysis of the NHSBT screening programme for infectious agents in deceased tissu...

Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome

European Journal of Haematology — Thu, 19 Nov 2009 00:00:00 +0100

(Source: European Journal of Haematology)

VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia

Haemophilia — Thu, 19 Nov 2009 00:00:00 +0100

Summary. Prophylactic treatment is recommended for severe haemophilia. Non-adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is to validate a new prophylactic treatment adherence scale entitled Validated Hemophilia Regimen Treatment Adherence Scale [ndash] Prophylaxis (VERITAS-Pro), a self-/parent-report questionnaire consisting of 24 questions on six (four-item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS-Pro for validation and reliability analysis; and observers were recruited for inter-rater reliability analysis. Validation measures included subjective adherence ratings...

Mechanical Ventilation and the Kidney

Blood Purification — Wed, 18 Nov 2009 23:00:00 +0100

Blood Purif 2010;29:52-68 (DOI:10.1159/000259585) (Source: Blood Purification)

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Upcoming Events

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

(Source: Transfusion and Apheresis Science)

Dengue virus during blood donation: Pre-screen using NS1 antigen

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Estimates for dengue transmission during blood donations have been upsetting in diverse geographical locations. During the 2004 dengue virus (DENV) outbreak in Cairns, Australia, the risk of collecting a viremic donation could have been as high as 1 in 1028 during the peak of the outbreak . Using a mathematical model and assuming a ratio of asymptomatic to symptomatic infections of 2:1–10:1, the risk for dengue-infected blood transfusions in Singapore, a city-state in Asia, during 2005 was estimated to be 1625–6/10,000 blood transfusions . In a tertiary care teaching hospital that provides care in Northeast Mexico, 800 blood donors were screened for DENV IgM, IgG using ELISA, DENV genome by reverse transcription polymerase chain reaction (RT-PCR). While 59% of donors were reactive for ...

The clinical trials section

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

In this issue of Transfusion and Apheresis Science we are introducing a new section which will address clinical trials. Dr. Ramlow from Rostock, Germany has agreed to take on the responsibility of Editor of this section. The purpose of this section will be to share information concerning proposed, ongoing or completed clinical trials with an international audience. We encourage our readers to let Dr. Ramlow know of any trials and/or provide their comments on such. He can be reached at: (Source: Transfusion and Apheresis Science)

The potential usefulness of thrombelastography in quality monitoring and quality improvement of blood components

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Thrombelastography (TEG) technology is a cell-based methodology for analysis of the viscoelastic changes that occur during coagulation of a whole blood sample in vitro, providing a unique opportunity to evaluate initiation, propagation, formation and stability of the clot strength of citrated blood and the derived haemostatic components. The potential clinical applications of modern TEG are well established. This brief report deals with additional potential applications of TEG in quality monitoring of haemostatic blood components, for clinical use. This is of particular relevance as with the recent technological advances, the TEG technology becomes well standardised and digitalisation of the procedure made it possible to be used as an essential tool in monitoring haemostasis in either labo...

Clinical trials for pathogen reduction in transfusion medicine: A review

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Abstract: Despite the implementation of highly sensitive methods for the detection of pathogens in donor blood products, the risk of transmission of infectious disease to transfusion recipients remains. Of greatest concern, and accounting for most of the risk, are newly-emerging pathogens for which screening assays do not yet exist or well-known pathogens for which testing regimens are not routinely employed. Furthermore, passive donor screening programs are unlikely to capture all potentially infective donors. A promising strategy to overcome these limitations is the proactive incapacitation of pathogens residing in donor units. Several unique pathogen reduction/inactivation (PR/PI) platforms have been developed and implemented in clinical settings. The aims of this article are to review:...

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Extracorporeal photo-apheresis for the treatment of steroid-resistant graft versus host disease

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Abstract: Acute and chronic graft versus host disease are frequent and potentially severe complications of allogeneic hematopoietic stem cell transplantation and are among the leading causes of non-relapse transplant-related mortality. For patients with steroid refractory disease, prognosis is particularly poor and although a variety of treatment options are available, responses are commonly transient and the side effects often intolerable. Since it was first introduced for the treatment of cutaneous T-cell lymphoma, extracorporeal photo-apheresis has been utilized as an immunomodulatory therapy for certain autoimmune diseases and solid organ transplant rejection. Recently, extracorporeal photo-apheresis has become a promising alternative for patients with graft versus host disease with di...

Biography

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Dr. Wagner obtained a B.S. in Chemistry (1977) at the University of Maryland and an M.S. (1979) and Ph.D. (1981) in Biophysics at the Pennsylvania State University. He joined the American Red Cross in 1989 as a scientist at the Holland Laboratory. He is a recipient of the Red Cross Tiffany Award and currently is a Director of Pathogen Management and Blood Product Improvement with the Blood Components Department. At the Holland Laboratory, Dr. Wagner has led groups which conduct developmental research in bacterial growth and detection in blood components, and in methods for pathogen reduction of blood components. He currently studies platelet preparation methods and storage conditions. He is the recipient of seven US patents and has authored or coauthored over 75 research articles. (Source:...

Illuminating blood components

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

The focus of this volume’s guest section is on the use of light with photochemicals to treat blood components. Some photochemical treatments of blood cause the formation of nucleic acid adducts and crosslinks in both leukocytes and infectious agents, ultimately leading to their apoptosis or inactivation, respectively. (Source: Transfusion and Apheresis Science)

The influence of riboflavin photochemistry on plasma coagulation factors

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:08 +0100

Conclusions: As with other pathogen reduction procedures for plasma products, treatment with riboflavin and UV light resulted in reduction in the activity levels of several pro-coagulant factors. Coagulation inhibitors are well preserved. (Source: Transfusion and Apheresis Science)

Motivators and barriers to blood donation in African American college students

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

Conclusions: African Americans female college students are willing to donate blood given convenience and support from their university. Educational campaigns to increase knowledge regarding the safety of the blood donation process and the ongoing needs of an adequate blood supply might be effective methods to increase blood donation. (Source: Transfusion and Apheresis Science)

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Homing of lin−/CD117+ hematopoietic stem cells

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

In this report, we describe the homing of hematopoietic stem cells (HSCs) to non-hematopoietic tissues in lethally irradiated (9Gy) hybrid mice transplanted intravenously with lin−/CD117+ bone marrow cells from ROSA26 mice. The numbers of CFU-GM in spleen of irradiated transplanted mice were well above the levels found in non-irradiated group as early as day 8 after transplant. On 12th day regeneration of lymphocytes was observed, an increase in granulocytes was detected as late as on 33rd day. Transplanted cells containing lacZ gene were detected in recipient mice by histochemistry and their location in the thymus, liver, stomach and ileum was followed during 33days post-transplantation. On 8 and 33days post-transplantation, we found massive presence of donor (lacZ+) cells in the thymic...

Blood transfusion therapy for 41 earthquake casualties

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

Conclusion: Blood transfusion was an effective therapy for the earthquake casualties. (Source: Transfusion and Apheresis Science)

The association of gender, age, body mass index, and vital signs in healthy plateletapheresis donors

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

Abstract: In order to determine the association between gender, age, body mass index and vital signs among healthy plateletapheresis donors, the mean and median values from the most recent donations of 236 plateletapheresis donors were calculated for age, body mass index (BMI), oral temperature, blood pressure (BP), and pulse. Values of these parameters were compared after stratification by gender, age, and BMI and multiple regression analysis between parameters performed. Gender, age, and BMI were associated with significant differences in vital signs of healthy plateletapheresis donors. (Source: Transfusion and Apheresis Science)

Anti-haptoglobin antibody detection after febrile non-hemolytic transfusion reactions in a non-haptoglobin-deficient patient

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

We describe herein a patient with FNHTR after the transfusion of leukoreduced single-donor apheresis platelet concentrates (LR-PC). (Source: Transfusion and Apheresis Science)

The effect of blood donation frequency on iron status

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

Conclusion: Adjusting the donation intervals is a way to prevent iron deficiency in blood donors. (Source: Transfusion and Apheresis Science)

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ESFH membership application form

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

(Source: Transfusion and Apheresis Science)

Editorial–Issue 41.3

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

The title of the theme in this issue is Illuminating Blood Components. This section, which was put together by one of the new members of the Editorial Board, Dr. Stephen Wagner, addresses issues related to exposure of blood components to various light sources. There is an interesting article on use of photopheresis in the treatment of Graft versus Host disease and this is followed by a review of the various clinical trials for pathogen reduction in Transfusion Medicine. The majority of the pathogen reduction methods involve exposure to either UV or other light sources. While a great many units of SDP and methylene blue treated plasma have been transfused in Europe, there are, in fact, few prospective clinical trials on these products; both amotosalen and riboflavin treated plasma are relat...

Editorial board/Publication information

Transfusion and Apheresis Science — Wed, 18 Nov 2009 14:25:07 +0100

(Source: Transfusion and Apheresis Science)

Apixaban: an emerging oral factor Xa inhibitor

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:14:11 +0100

Abstract Apixaban, an oral direct factor Xa inhibitor, is currently in late stage clinical development for the prevention and treatment of thromboembolic diseases. In comparison with current treatment standards for venous thromboembolism (VTE) prophylaxis, apixaban has shown decreased rates of clinically significant bleeding with mixed results in terms of non-inferiority for VTE events. Secondary treatment of VTE with apixaban is currently in phase III clinical study after earlier trials showed comparable safety and efficacy outcomes. The APPRAISE-1 trial, a phase II investigation of apixaban versus placebo following acute coronary syndrome showed a higher risk of clinically significant bleeding in addition to a trend toward decreased ischemic events. A large, internationa...

Prevalence, clinical correlates and treatment of permanent atrial fibrillation among the elderly: insights from the first prospective population-based study in rural Greece

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:14:10 +0100

Abstract To investigate the prevalence of permanent atrial fibrillation (AF), its clinical associated conditions and treatment status in the elderly population in rural Greece. 720 people (46.1% males) older than 65 years (mean age: 72.5 ± 5.7 years) living in four villages in rural Greece were screened with an electrocardiogram (response rate: 90.5%) for the presence of permanent AF. They underwent a physical examination, including blood pressure (BP) measurement, and body mass index (BMI) calculation, in addition to an interview about their medical history, physical activity, smoking habits, alcohol consumption and medication use. Subjects with AF for whom anticoagulants were contraindicated were identified and stroke risk stratification was performed...

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Proceedings of the 10th National Conference on Anticoagulant Therapy

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:14:07 +0100

Content Type Journal ArticleDOI 10.1007/s11239-009-0427-yAuthors David A. Garcia, University of New Mexico Health Sciences Center, 1 University of New Mexico MSC Anticoagulation Clinic 10 5550 Albuquerque NM 87131 USA Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis and Thrombolysis)

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:14:02 +0100

This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival. Content Type Journal ArticleDOI 10.1007/s11239-009-0419-yAuthors Giuseppe De Luca, “Maggiore della Carità” Hospital, Eastern Piedmont University Division of Cardiology Novara ItalyC. Michael Gibson, Brigham & Women’s Hospital TIMI Study Group, Cardiovascular Division Boston MA USAFrancesco Bellandi, Prato Hospital Division of Cardiology Prato ItalyMarko Noc, University Medical Center Center for Intensive Internal Medicine Ljubljana SloveniaMauro Maioli, Prato Hospital Division of Cardiology Prato ItalySimona Zorman, University Medical Center Center for Intensive Internal Medicine Ljubljana SloveniaUw...

What you should know about the 2008 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th) on Antithrombotic and Thrombolytic Therapy

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:13:57 +0100

The objective of this article is to help answer ten common clinical questions frequently faced by anticoagulation management services. Content Type Journal ArticleDOI 10.1007/s11239-009-0415-2Authors Scott Kaatz, Henry Ford Hospital Department of Medicine Detroit MI 48202 USA Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis and Thrombolysis)

Impact of diabetes on long-term outcome in STEMI patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors and BMS or DES

Journal of Thrombosis and Thrombolysis — Wed, 18 Nov 2009 05:13:52 +0100

This study shows that among STEMI patients undergoing primary angioplasty with Gp IIb–IIIa inhibitors, diabetes is associated with worse long-term mortality, reinfarction, and IST, even with DES implantation, that, however, were able to equalize the outcome in terms of TVR as compared to non diabetic patients. Content Type Journal ArticleDOI 10.1007/s11239-009-0420-5Authors Giuseppe De Luca, Eastern Piedmont University Division of Cardiology, Ospedale “Maggiore della Carità” C.so Mazzini 18 28100 Novara ItalyRosario Sauro, “S.G. Moscati” Division of Cardiology Avellino ItalyAttilio Varricchio, “S.G. Moscati” Division of Cardiology Avellino ItalyMichele Capasso, “S.G. Moscati” Division of Cardiology Avellino ItalyTonino Lanzillo, “S.G. Moscati” Division of Card...

Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study

Annals of Hematology — Wed, 18 Nov 2009 00:06:17 +0100

Abstract The clinical efficacy and safety of a four-drug combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone was assessed for patients with relapsed or refractory multiple myeloma. Seventy patients received at least two cycles of treatment with bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m2 orally on days 1–4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m2 intravenously on days 1, 4, 8, and 11. The overall best response rate was 88%, with 46% complete response, 9% very good partial response, and 33% partial response. After a median follow-up of 12.6 months, the median progression-free survival (PFS) was 14.6 months with a 3-year PFS of 14% and the median overal...

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Erratum to: Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia

Annals of Hematology — Wed, 18 Nov 2009 00:06:16 +0100

Content Type Journal ArticleCategory ErratumDOI 10.1007/s00277-009-0860-1Authors Antonio R. Lucena-Araujo, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilDanielle L. Souza, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilFabio Morato de Oliveira, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilMariana Tereza Lira Benicio, Univer...

Cytogenetic features and prognosis analysis in Chinese patients with myelodysplastic syndrome: a multicenter study

Annals of Hematology — Wed, 18 Nov 2009 00:06:14 +0100

In this study, we retrospectively analyzed clinical and cytogenetic data from 435 Chinese adult primary MDS patients. In addition, we evaluated the prognostic value of the World Health Organization classification as well as six prognostic scoring systems in these patients. The median follow-up time was 25.1 months (5.5–53.2). Of the 435 patients, 186 (42.8%) had died and 40 (9.2%) had progressed to acute myeloid leukemia. Multivariate analysis identified older age, higher percent of marrow blasts, and poor-risk IPSS cytogenetics as characteristics associated with worse survival and higher risk of leukemia transformation. Low platelets, hemoglobin, and mean corpuscular volume were independent factors associated only with worse survival. Among the 424 patients in whom the result...

Hyperlipidemic myeloma: review of 53 cases

Annals of Hematology — Wed, 18 Nov 2009 00:06:14 +0100

In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0849-9Authors Benjamin Misselwitz, University Hospital Zürich Department of Internal Medicine Rämistr. 100 8091 Zürich SwitzerlandJeroen S. Goede, University Hospital Zürich Clinic of Haematology Rämistr. 100 8091 Zürich SwitzerlandBernhard C. Pestalozzi, University Hospital Zürich Clinic of Oncology Rämistr. 100 8091 Zürich SwitzerlandUrs Schanz, University Hospital Zürich Clinic of Haematology Rämistr. 100 8091 Zürich SwitzerlandJörg D. Seebach, University Hospital...

In vitro comparison of platelet storage in plasma and in four platelet additive solutions, and the effect of pathogen reduction: a proposal for an in vitro rating system

Vox Sanguinis — Wed, 18 Nov 2009 00:00:00 +0100

Conclusion PLT concentrates in plasma, SSP+ and Composol scored better using an arbitrary rating system as PLTs stored in T-Sol or InterSol; PR further impaired rating parameters. The applicability of these differences in rating for clinical effects needs a clinical study. (Source: Vox Sanguinis)

Hemostasis and inflammation: two of a kind?

Thrombosis Journal — Wed, 18 Nov 2009 00:00:00 +0100

Hemostasis is a defense mechanism to stop bleeding. Activated by vessel wall injury, it consists of intertwined activation of platelets and the coagulation cascade, tightly controlled by natural anticoagulants and the fibrinolytic system. Inflammation aims at restoring the integrity of damaged or threatened tissues, most frequently because of injury or infectious pathogens. Both are intimately coupled. (Source: Thrombosis Journal)

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Cubital tunnel syndrome in patients with haemophilia

Haemophilia — Wed, 18 Nov 2009 00:00:00 +0100

Summary. Elbow is the second most common joint involved in patients with haemophilia; however, there is little data about the involvement of ulnar nerve at elbow in patients with haemophilic arthropathy. The purpose of this study was to address this problem in the elbow and evaluate the results of anterior subcutaneous transposition of the ulnar nerve in a small group of patients with haemophilia who had been managed in two institutions. Information on six patients who were diagnosed with tardy ulnar nerve palsy in two institutions was retrospectively collected. All patients suffered form severe haemophilia A. Anterior subcutaneous transposition of the ulnar nerve had been performed in all except one. The mean age of the patients at the time of procedure was 45.8 years and the mean duratio...

The optimal mode of delivery for the haemophilia carrier expecting an affected infant is vaginal delivery

Haemophilia — Wed, 18 Nov 2009 00:00:00 +0100

Summary. The optimal mode of delivery of a haemophilia carrier expecting a child is still a matter of uncertainty and debate. The aim of this commentary/review is to suggest that normal vaginal delivery should be the recommended mode of delivery for the majority of carriers, based on review of studies on obstetric aspects of haemophilia. About 2.0[ndash]4.0% of all haemophilia boys born in countries with a good standard of health care will suffer from ICH during the neonatal period. This is an average figure including all modes of delivery and regardless of whether the carrier status of the mother or the haemophilia status of the foetus was known or not at the time of delivery. On the basis of current literature, one may conclude that the risk of serious bleeding in the neonate affected wi...

Major orthopaedic surgeries for haemophilia with inhibitors using rFVIIa

Haemophilia — Wed, 18 Nov 2009 00:00:00 +0100

This report is the largest clinical report on major orthopaedic surgeries at a single institute. We have concluded that the combination of bolus and continuous infusion of rFVIIa is safe and effective, and more convenient to administer than simple bolus infusion therapy to achieve haemostasis at peri-operative periods. In addition, our data also concurs with the data of several previous reports which showed that orthopaedic surgery for haemophilia patients with inhibitors by means of rFVIIa is safe and effective. (Source: Haemophilia)

Mammography Recommendation Draws Strong Responses

MedPage Today Hematology/Oncology — Tue, 17 Nov 2009 23:08:49 +0100

A recommendation to delay breast cancer screening with mammography until age 50 drew a mix of strong dissent and support from organizations and individuals that have a particular interest in the topic. (Source: MedPage Today Hematology/Oncology)

Syndrome Misdiagnosed as Neurofibromatosis (CME/CE)

MedPage Today Hematology/Oncology — Tue, 17 Nov 2009 19:49:35 +0100

The recently discovered Legius syndrome may be underdiagnosed because doctors confuse it with neurofibromatosis type 1, a genetically distinct but similar disorder, a new study found. (Source: MedPage Today Hematology/Oncology)

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Editorial Board

Experimental Hematology — Tue, 17 Nov 2009 14:20:43 +0100

(Source: Experimental Hematology)

How Cells Tolerate DNA Damage - MDC Researchers Identify Start Signal For Cell Survival Program

Lymphoma / Leukemia News From Medical News Today — Tue, 17 Nov 2009 13:00:00 +0100

Cancer researchers of the Max DelbrÃ¼ck Center for Molecular Medicine (MDC) Berlin-Buch have gained new insights into how cells react to DNA damage. Dr. Michael Stilmann, Dr. Michael Hinz and Professor Claus Scheidereit have shown that the protein PARP-1, which detects DNA damage within seconds, activates the transcription factor NF-kappaB, a well-known regulator of gene expression. NF-kappaB triggers a survival program, which blocks programmed cell death. (Source: Lymphoma / Leukemia News From Medical News Today)

Co-Founder Of Microsoft Diagnosed With Non-Hodgkin's Lymphoma

Lymphoma / Leukemia News From Medical News Today — Tue, 17 Nov 2009 11:00:00 +0100

Paul Allen who co-founded the computer giant Microsoft with Bill Gates in the 1970s has been diagnosed with Non-Hodgkin's Lymphoma, 25 years after surviving Hodgkin's lymphoma. The news was announced in a memo to the staff of Allen's company Vulcan, by CEO Jody Allen, who is also Paul Allen's sister. A copy of the memo was also sent to the media. (Source: Lymphoma / Leukemia News From Medical News Today)

EntreMed's ENMD-2076 Active In Solid And Hematological Cancers

Lymphoma / Leukemia News From Medical News Today — Tue, 17 Nov 2009 09:00:00 +0100

EntreMed, Inc. ( ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer announced the presentation of data for the Phase 1 study for its Aurora A/angiogenic kinase inhibitor, ENMD-2076, in leukemia patients. The Company also announced that it has selected ovarian cancer as an initial Phase 2 indication. (Source: Lymphoma / Leukemia News From Medical News Today)

Post-transfusion purpura caused by anti-HPA-3a antibodies that are only detectable using whole platelets in the platelet immunofluorescence test

Transfusion Medicine — Tue, 17 Nov 2009 00:00:00 +0100

(Source: Transfusion Medicine)

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Mean cell volume of neutrophils and monocytes compared with C-reactive protein, interleukin-6 and white blood cell count for prediction of sepsis and nonsystemic bacterial infections

Clinical and Laboratory Haematology — Tue, 17 Nov 2009 00:00:00 +0100

Clinicians are in need of better diagnostic markers for rapid diagnosis of severe infections. Therefore, we studied the diagnostic significance of mean cell volume of neutrophils (MNV) and monocytes (MMV) compared with Interleukin-6 (IL-6), C-reactive protein (CRP) and white blood cell count for predicting systemic clinical infection (sepsis). MNV and MMV were obtained by volume conductivity scatter (VCS) technique of the Coulter LH 750 hematology analyzer during automated differential counts, and blood samples from patients with sepsis (n = 37), nonsystemic bacterial infections (n = 39) and controls (n = 48) were studied. We observed a significant increase in MNV and MMV in the sepsis group compared with limited infections and controls. However, at a designated cut-off point of 250 pg/ml,...

Successful treatment of autoimmune and lymphoproliferative complications of patients with intrinsic B-cell immunodeficiencies with Rituximab

British Journal of Haematology — Tue, 17 Nov 2009 00:00:00 +0100

The heterogeneous group of primary immunodeficiencies requires personalized diagnosis and therapy to acheive an optimal outcome for each patient. This was exemplified by two patients with intrinsic B-cell class-switch defects (subclass of Hyper-IgM syndromes), where lymphoproliferation and autoimmunity determined the clinical course for many years due to lack of exact diagnosis. Based on genetics or a novel functional diagnostic approach, a definite individual diagnosis was established for each patient and they started Rituximab therapy. Autoimmune phenomena and generalized lymphadenopathy disappeared and remained well controlled during the observation period (3[ndash]4 years) without adverse effects. Quality of life increased remarkably in both patients. (Source: British Journal of Haemat...

Panel Puts Off Mammography until Age 50 (CME/CE, with audio)

MedPage Today Hematology/Oncology — Mon, 16 Nov 2009 21:00:00 +0100

Women younger than 50 do not need routine screening mammography for breast cancer, according to new government recommendations, which constitute a departure from other clinical guidelines for breast cancer prevention. (Source: MedPage Today Hematology/Oncology)

Smoking-Related Bladder Cancer on the Rise (CME/CE)

MedPage Today Hematology/Oncology — Mon, 16 Nov 2009 20:00:00 +0100

Smokers appear to be at nearly four times the risk of bladder cancer than they were in the mid-1990s, possibly stemming from changes to the design and composition of cigarettes in the 1960s and 1970s, a new study found. (Source: MedPage Today Hematology/Oncology)

Finding May Give Hope To More Leukemia Patients So They May Live Cancer-Free

Lymphoma / Leukemia News From Medical News Today — Mon, 16 Nov 2009 08:00:00 +0100

A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning. This finding has the potential to change the current medical practice of using one unit of UCB for treatment of patients who are at high risk for recurrence of leukemia and other cancers of the blood and bone marrow. Michael Verneris, M.D. (Source: Lymphoma / Leukemia News From Medical News Today)

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Download the classic folksong Shenandoah to your iPod or Zune, and make a donation to the the IMF.

International Myeloma Foundation — Mon, 16 Nov 2009 05:00:00 +0100

This holiday season, why not do something for yourself and the IMF. For every 99-cent download of Shenandoah, beautifully sung by singer-songwriter Taylor Barton, she will donate her royalties to the IMF. (Source: International Myeloma Foundation)

Application of an expanded multiplex genotyping assay for the simultaneous detection of Hemoglobin Constant Spring and common deletional α-thalassemia mutations

Clinical and Laboratory Haematology — Mon, 16 Nov 2009 00:00:00 +0100

Hemoglobin Constant Spring (HbCS) is the most common nondeletional [alpha]-thalassemia variant causing HbH disease, making its detection crucial in populations at risk. Universal newborn screening for HbH is carried out in California. Identification of [alpha]-thalassemia genotypes responsible for HbH and HbH-CS requires rapid, accurate and cost-effective genotyping methods suitable for population screening. We incorporated the HbCS mutation into our existing seven-plex genotyping assay for common [alpha]-thalassemia deletions. To assess the feasibility and diagnostic utility of this expanded multiplex gap-PCR assay, we determined genotypic frequencies of HbCS in samples referred for [alpha]-thalassemia testing between 1 January 2006 and 31 December 2008. During the 3-year study period, 14...

Health-related quality of life following haematopoietic cell transplantation: patient education, evaluation and intervention

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

Health-related quality of life (QOL) is a vital concern in the pre-treatment consent process and post-treatment care of recipients of haematopoietic cell transplantation (HCT). We propose that comprehensive care of such patients requires an integration of knowledge of the impact of HCT on QOL, assessment of QOL, as well as resources available for intervention. This knowledge may significantly improve patient care when incorporated into daily clinical practice in the transplant setting. As a framework for this approach, this article reviews the literature on QOL after allogeneic and autologous HCT for adults with haematological malignancies. We then discuss evidence in support of the beneficial impact of clinical QOL assessment, and finally evaluate behavioural interventions that show promi...

Favourable outcome of pneumonia due to novel influenza A/H1N1 2009 virus in a splenectomised adult patient undergoing therapy for non-Hodgkin lymphoma

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

(Source: British Journal of Haematology)

Fludarabine, Bortezomib, Myocet® and rituximab chemotherapy in relapsed and refractory mantle cell lymphoma

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

(Source: British Journal of Haematology)

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Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

Progressive degeneration of the central nervous system leading to the loss of neuromotor, neurophysiological and cognitive abilities is the fundamental clinical problem in patients with many inherited metabolic diseases (IMD). Worldwide experience shows that morbidity, quality of life, and survival in these patients can be improved by allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed early in the course of the disease. At present, while available for some conditions, exogenous enzyme replacement therapy is unable to correct cognitive and central nervous system disease because of its inability to cross the blood-brain barrier. In contrast, HSCT allows donor-derived, enzyme-producing cells to migrate to the brain and other organs providing a permanent en...

Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

This study identified a structure that deeply affects this response, because of its impact on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone remodelling compartment (BRC). These canopies are frequently disrupted in myeloma, and this disruption correlates with increased proximity and density of myeloma cells. In vitro evidence indicates that this disruption may be due to direct contact between myeloma and BRC canopy cells. Importantly, this disruption and increased proximity and density of myeloma cells coincides with key myeloma-induced...

Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma

British Journal of Haematology — Mon, 16 Nov 2009 00:00:00 +0100

We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1·3 mg/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1·0 mg/m2, dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%[ge] very good partial response. Twenty-two patients have undergone stem-cell transplantation. After a median follow-up of 20·9 months, five patients have died; none was induction therapy-related. Median event-free survival (EFS) and overall survival (OS) have ...

Development of national performance measures on the prevention and treatment of venous thromboembolism

Journal of Thrombosis and Thrombolysis — Sat, 14 Nov 2009 20:48:50 +0100

Abstract Venous thromboembolism (VTE) remains a significant public health problem in the United States, particularly for hospitalized patients. Approximately two-thirds of all VTE events are associated with recent hospitalization. Despite the well-known risks of VTE, multiple studies have demonstrated underuse of VTE prophylaxis and clinicians often do not provide evidence-based care for those patients with confirmed VTE. In January 2005, the National Quality Forum initiated a project to develop national consensus standards on organization policies, preferred practices, and performance measures for the prevention and treatment of VTE. In addition to the organizational policy statement and 17 preferred practices, eight national performance measures addressing various aspect...

Combined warfarin–aspirin therapy: what is the evidence for benefit and harm and which patients should (and should not) receive it?

Journal of Thrombosis and Thrombolysis — Sat, 14 Nov 2009 20:48:50 +0100

The objectives of this review are to describe the characteristics of patients who are receiving combined warfarin–aspirin therapy, to summarize the evidence for the therapeutic benefit and harm of combined warfarin–aspirin, and to provide practical guidelines as to which patients should (or should not) receive such treatment. Content Type Journal ArticleDOI 10.1007/s11239-009-0413-4Authors Marco P. Donadini, McMaster University and St Joseph’s Healthcare Department of Medicine Hamilton ON L8N 4A6 CanadaJames D. Douketis, McMaster University and St Joseph’s Healthcare Department of Medicine Room F-544, 50 Charlton Ave. East Hamilton ON L8N 4A6 Canada Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis a...

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Oncostatin M and leukemia inhibitory factor increase hepcidin expression in hepatoma cell lines.

International Journal of Hematology — Sat, 14 Nov 2009 00:00:00 +0100

In conclusion, we demonstrated that OSM and LIF can induce hepcidin expression mainly through the JAK/STAT pathways. Further studies are warranted to evaluate the clinical significance of OSM and LIF in the development of anemia in various inflammatory diseases. PMID: 19915946 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein-Barr virus infection.

International Journal of Hematology — Sat, 14 Nov 2009 00:00:00 +0100

Authors: Wada T, Yokoyama T, Nakagawa H, Asai E, Toga A, Sakakibara Y, Shibata F, Tone Y, Shimizu M, Toma T, Yachie A In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56(+) NK cells in the fluid compared with a simple mosquito allergy, in which the majority of...

Central nervous system T-cell lymphoma in acquired immunodeficiency syndrome

British Journal of Haematology — Sat, 14 Nov 2009 00:00:00 +0100

(Source: British Journal of Haematology)

The financial viability of an anticoagulation clinic: a discussion from the anticoagulation forum meeting, May, 2009

Journal of Thrombosis and Thrombolysis — Fri, 13 Nov 2009 18:27:56 +0100

Content Type Journal ArticleDOI 10.1007/s11239-009-0417-0Authors Henry I. Bussey, The University of Texas at Austin College of Pharmacy Austin TX USA Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis and Thrombolysis)

Angiotensin II up-regulates CX3CR1 expression in THP-1 monocytes: impact on vascular inflammation and atherogenesis

Journal of Thrombosis and Thrombolysis — Fri, 13 Nov 2009 18:27:55 +0100

In conclusion, angiotensin II increases the rate of CX3CR1-positive THP-1 cells. By extrapolating this in vitro observation to disease mechanisms, we speculate that angiotensin II induces up-regulation of CX3CR1 and promotes firm adhesion of circulation CX3CR1-positive monocytes on CX3CL1 expressing endothelial cells inducing vascular inflammation and atherogenesis. Content Type Journal ArticleDOI 10.1007/s11239-009-0424-1Authors Stavros Apostolakis, University of Crete Department of Clinical Virology, Faculty of Medicine Heraklion GreeceZacharenia Vlata, Institute of Molecular Biology and Biotechnology Department of Applied Biochemistry and Immunology FORTH, Heraklion Crete GreeceKonstantina Vogiatzi, University of Crete Department of Clinical Virology, Faculty of Medicine Her...

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Assessment of validity of INR system for patients with liver disease associated with viral hepatitis

Journal of Thrombosis and Thrombolysis — Fri, 13 Nov 2009 18:27:54 +0100

Abstract International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in all prognostic models of survival, the classification of CHILD-Pugh or Meld. However, the mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation. Our aim was to assess the validity of the INR system for patients with liver disease associated with viral hepatitis. We prospectively collected blood samples from 61 patients with liver disease associated with viral hepatitis; control patients were on warfarin (n = 20). PTs were measured on a STA-R coagulometer with six thromboplastin reagents, and INRs were calculated using instrument-spec...

Test for Platelet Contamination Wins FDA Nod

MedPage Today Hematology/Oncology — Fri, 13 Nov 2009 18:17:51 +0100

The FDA has approved the first rapid test for bacterial contamination of bagged platelets, which can be performed immediately before they are transfused into patients. (Source: MedPage Today Hematology/Oncology)

Recent advances in the understanding of iron metabolism and iron-related diseases.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Hoffbrand AV PMID: 19907143 [PubMed - in process] (Source: Acta Haematologica)

The role of hepcidin in iron metabolism.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Nemeth E, Ganz T Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemias, and hepatitis C. Hepcidin excess is associated with anemia of inflammation, chronic kidney disease and iron-refractory iron deficiency anemia. Diagnostic and therapeutic applications of this new knowledge are beginning to emerge. Dr. Ernest Beutler played a significant role in advancing our understanding of the function of hepcidin. This review is dedicated to his memory. PMID: 19907144 [PubMed - in process] (Source: Acta Haematologica)

Role of matriptase-2 (TMPRSS6) in iron metabolism.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Lee P Iron, an essential element for life, is regulated primarily at the level of uptake, storage, and transport in order to maintain sufficient availability for normal physiology. The key protein in iron homeostasis is a 25-amino-acid peptide, hepcidin, which modulates the amount of iron in the circulation by binding and promoting the degradation of the iron exporter ferroportin. Given the central importance of hepcidin, recent studies have focused on how iron is sensed and how the iron signal is transmitted to hepcidin. Mutations in a type II serine protease, matriptase-2/TMPRSS6, were recently identified to be associated with severe iron deficiency caused by inappropriately high levels of hepcidin expression. A key biologically relevant substrate for the proteolytic activit...

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Iron deficiency, Helicobacter infection and gastritis.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Hershko C, Ronson A Despite elegant regulatory mechanisms, iron deficiency anemia (IDA) remains one of the most common nutritional deficiencies of mankind. Iron deficiency is the result of an interplay between increased host requirements, limited external supply, and increased blood loss. When related to increased physiologic needs associated with normal development, iron deficiency is designated physiologic or nutritional. By contrast, pathological iron deficiency, with the exception of gross menorrhagia, is most often the result of gastrointestinal disease associated with abnormal blood loss or malabsorption. If gastroenterologic evaluation fails to disclose a likely cause of IDA, or in patients refractory to oral iron treatment, screening for celiac disease (anti-tissue tra...

Anemia of chronic disease (anemia of inflammation).

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Agarwal N, Prchal JT Mild-to-moderate anemia often develops in the setting of acute or chronic immune activation and is termed anemia of chronic disease (ACD) or anemia of inflammation. Anemia of chronic disease is the second most common type of anemia (after anemia of iron deficiency) and results in increased morbidity and mortality of the underlying disease. Anemia of chronic disease is mediated by inflammatory cytokines and is characterized by low serum iron (hypoferremia) and often increased reticuloendothelial stores of iron. Hepcidin is the master regulator of iron homeostasis and its synthesis is inhibited by iron deficiency and stimulated by inflammation. The serum hepcidin level is useful in identifying iron deficiency in patients with ACD. Successful treatment of the...

The anemia of heart failure.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Silverberg DS, Wexler D, Palazzuoli A, Iaina A, Schwartz D Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of eryt...

Mitochondrial iron metabolism and sideroblastic anemia.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Sheftel AD, Richardson DR, Prchal J, Ponka P Sideroblastic anemias are a heterogeneous group of disorders, characterized by mitochondrial iron overload in developing red blood cells. The unifying characteristic of all sideroblastic anemias is the ring sideroblast, which is a pathological erythroid precursor containing excessive deposits of non-heme iron in mitochondria with perinuclear distribution creating a ring appearance. Sideroblastic anemias may be hereditary or acquired. Hereditary sideroblastic anemias are caused by defects in genes present on the X chromosome (mutations in the ALAS2, ABCB7, or GRLX5 gene), genes on autosomal chromosomes, or mitochondrial genes. Acquired sideroblastic anemias are either primary (refractory anemia with ring sideroblasts, RARS, represent...

The natural history of untreated HFE-related hemochromatosis.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Adams PC Hemochromatosis has generally been considered to be a genetic disease in which progressive iron accumulation over many years can lead to cirrhosis of the liver, hepatocellular carcinoma, diabetes, cardiomyopathy, and arthropathy. Iron depletion by phlebotomy has been the recommended therapy although a randomized trial of phlebotomy versus no treatment has never been reported. Since the discovery of the HFE gene in 1996, it has been possible to predict the risk of developing iron overload by a simple blood test to detect C282Y homozygotes of the HFE gene. The application of the hemochromatosis genetic test in large population studies often initiated to investigate other diseases has provided a fascinating glimpse into the natural history of untreated C282Y homozygotes ...

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Rare types of genetic hemochromatosis.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Camaschella C, Poggiali E Most types of genetic hemochromatosis are due to mutations in the HFE gene, although similar iron overload and organ damage can also result from mutations in genes other than HFE in rare types of hemochromatosis. Non-HFE hemochromatoses have been divided into two subgroups with distinctive features. The first includes juvenile and TFR2-related hemochromatoses that, similar to HFE hemochromatosis, show recessive inheritance, increased transferrin saturation, iron storage in hepatocytes and responsiveness to phlebotomy. Disorders in this subgroup, although differing regarding the severity of iron overload and/or the age at presentation, are all either due to hepcidin deficiency or to the inability to increase hepcidin levels according to iron stores. Th...

Role of T2* magnetic resonance in monitoring iron chelation therapy.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Carpenter JP, Pennell DJ The monitoring of chelation therapy is a very important part of the management of transfusion-dependent patients. Classical methods of monitoring iron loading are either unreliable or unable to detect important myocardial siderosis which can predispose to the development of cardiac complications such as heart failure. The development of the T2* technique using cardiovascular magnetic resonance has allowed clinicians to have a reliable method for measuring cardiac iron to guide chelation therapy. T2* can identify early those patients who are at risk of developing cardiac complications, enabling personalised, tailored therapy to avoid potential problems. PMID: 19907152 [PubMed - in process] (Source: Acta Haematologica)

Deferiprone chelation therapy for thalassemia major.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Galanello R, Campus S Iron overload is one of the major causes of morbidity in patients with thalassemia major. Deferiprone (DFP), an orally active iron chelator, emerged from an extensive search for new drugs to treat iron overload. Comparative studies have shown that at comparable doses the efficacy of DFP in removing body iron is similar to that of desferoxamine (DFO). In retrospective and prospective studies, DFP monotherapy was significantly more effective than DFO in the treatment of myocardial siderosis in thalassemia major. DFP can be used in combination with DFO in the management of severe iron overload. This chelation regimen is tolerable and attractive for patients unable to comply with standard DFO infusions or with inadequate response to DFP monotherapy. DFP has a...

Deferasirox (Exjade) for the treatment of iron overload.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Cappellini MD, Taher A Deferasirox is a once-daily oral iron chelator with established dose-dependent efficacy in both adult and pediatric patients with transfusional iron overload. The clinical development program has demonstrated the efficacy of deferasirox for up to 4.5 years of treatment in patients with various underlying anemias, including beta-thalassemia, myelodysplastic syndromes, sickle cell disease, aplastic anemia, and other rare anemias. In addition to reducing key indicators of total body iron levels (serum ferritin, liver iron concentration, and toxic labile plasma iron), deferasirox has also demonstrated the ability to remove cardiac iron and prevent future cardiac iron accumulation. Emerging long-term data confirm the tolerability profile of deferasirox, and d...

Iron metabolism and iron chelation in sickle cell disease.

Acta Haematologica — Fri, 13 Nov 2009 15:22:05 +0100

Authors: Walter PB, Harmatz P, Vichinsky E This review highlights recent advances in iron metabolism that are relevant to sickle cell disease (SCD). SCD is a common hemoglobinopathy that results in chronic inflammation. Improved understanding of how iron metabolism is controlled by proteins such as hepcidin, ferroportin, hypoxia-inducible factor 1, and growth differentiation factor 15 have revealed how they are involved in the organ toxicity of SCD. SCD patients have lower levels of non-transferrin-bound iron (NTBI) relative to other hemoglobinopathies, such as thalassemia. Care for SCD now commonly uses transfusion that results in iron overload and necessitates the need for chelation. New oral chelation therapy using deferasirox (Exjade/ICL670) appears to be safe and may even lower th...

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The aging population poses a global challenge for blood services.

Transfusion — Fri, 13 Nov 2009 00:00:00 +0100

CONCLUSIONS: A large part of the variation in RBC use per capita can be explained by the age distribution of the different populations and not by the different national and regional treatment policies and protocols used. If current efforts are not enough to serve the changing population demographic and if increasing demands for blood products cannot be met, there is need to consider unprecedented measures such as reversing certain donor deferrals or even exporting blood from country to country. PMID: 19912582 [PubMed - as supplied by publisher] (Source: Transfusion)

The quality of stored umbilical cord and adult-donated whole blood in Mombasa, Kenya.

Transfusion — Fri, 13 Nov 2009 00:00:00 +0100

CONCLUSION: Variable volumes of UC-WB can be stored for 35 days without prestorage processing and further work into its suitability for transfusion to children is justified. The quality of conventional AD-WB is a concern and needs further evaluation. PMID: 19912583 [PubMed - as supplied by publisher] (Source: Transfusion)

Declining hepatitis C virus (HCV) prevalence in pregnant women: impact of anti-HCV screening of donated blood.

Transfusion — Fri, 13 Nov 2009 00:00:00 +0100

CONCLUSION: Anti-HCV screening of donated blood and hygienic improvements have markedly decreased HCV infection of pregnant women with a transfusion history; however, 70% of anti-HCV-reactive women were deemed to be infected via routes other than transfusion. PMID: 19912584 [PubMed - as supplied by publisher] (Source: Transfusion)

Direct assessment of cytomegalovirus transfusion-transmitted risks after universal leukoreduction.

Transfusion — Fri, 13 Nov 2009 00:00:00 +0100

CONCLUSION: Among all 46 baseline seronegative recipients and 1316 evaluable transfusions, the calculated overall CMV-TTD risk was up to 6.5% (95% confidence interval [CI], 1.0%-18.0%) in terms of TRs and up to 0.23% (95% CI, 0.06%-0.62%) in terms of non-CMV-screened leukoreduced cellular products. In summary, after universal leukoreduction, CMV-TTD, while uncommon, may still occur. PMID: 19912585 [PubMed - as supplied by publisher] (Source: Transfusion)

Long-term storage of peripheral blood stem cells frozen and stored with a conventional liquid nitrogen technique compared with cells frozen and stored in a mechanical freezer.

Transfusion — Fri, 13 Nov 2009 00:00:00 +0100

CONCLUSION: In vitro measurements indicate that PBSCs can be successfully frozen and stored using a combination of DMSO and HES providing smaller amounts of DMSO and allowing simplified freezing and storage conditions. PMID: 19912586 [PubMed - as supplied by publisher] (Source: Transfusion)

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Compounds of the anthracycline family of antibiotics elevate human gamma-globin expression both in erythroid cultures and in a transgenic mouse model.

Blood Cells, Molecules & Diseases — Fri, 13 Nov 2009 00:00:00 +0100

We examined the effect of the anthracyclines aclarubicin, bleomycin, daunorubicin, doxorubicin and idarubicin on human gamma- and beta-globin promoter activity in an in vitro luciferase assay, ex vivo in erythroid cultures and in vivo in transgenic mice carrying the human gamma-globin gene. Effects in erythroid liquid cultures derived from healthy donors were assayed by evaluating HbF production with high performance liquid chromatography and by measuring mRNA levels of the globin genes and the proportion of erythroblasts containing HbF. Compounds testing positive in the in vitro and ex vivo assays were applied to erythroid cultures derived from thalassaemic patients. Doxorubicin, idarubicin and daunorubicin increased HbF production in cultures of both, healthy and thalassaemic donors. Dau...

The battlefield of perforin/granzyme cell death pathways.

Journal of Leukocyte Biology — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Hoves S, Trapani JA, Voskoboinik I A pore-forming protein, PRF, and serine proteases, Grz, are key effector molecules of CL. These toxins are stored within secretory granules, which exocytose their contents in response to immune synapse formation between the CL and virus-infected or transformed target cell. There, PRF and Grz synergize to induce various apoptotic death pathways and to maintain immune homeostasis. Mechanistic aspects of the synergy and apoptotic mechanisms are still not fully understood, and the current review will address some of the hotly debated controversies in the field. PMID: 19915166 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)

Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.

Journal of Leukocyte Biology — Fri, 13 Nov 2009 00:00:00 +0100

In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil --> blood --> BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR2 SHM followed different strategies to provide appropriate amino acid changes, but both exhibited maximal resistance to incorporating drastic molecular alterations in the...

Multiple Myeloma Involving Skin and Pulmonary Parenchyma after Autologous Stem Cell Transplantation

Journal of Hematology and Oncology — Fri, 13 Nov 2009 00:00:00 +0100

Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation. (Source: Journal of Hematology and Oncology)

The potential role of epigenetic therapy in multiple myeloma

British Journal of Haematology — Fri, 13 Nov 2009 00:00:00 +0100

This review describes the role that epigenetic changes play in the pathogenesis of cancer, concentrating on the plasma cell malignancy multiple myeloma, and highlights recent findings regarding the efficacy of epigenetic therapeutic agents in laboratory studies and clinical trials. DNA methylation is altered in a wide range of cancers with hypermethylation of CpG islands associated with silencing of tumour suppressor genes. Genes found to be silenced by methylation in myeloma samples include VHL, TP53, CDKN2A, and TGFBR2. Myeloma is linked to the overexpression of a histone methylatransferase (MMSET) and inactivating mutations of a histone demethylase (UTX), suggesting that the regulation of histone methylation is a potential therapeutic target. Abnormal expression of histone deacetylases ...

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Serum granulysin as a possible biomarker of natural killer cell neoplasms

British Journal of Haematology — Fri, 13 Nov 2009 00:00:00 +0100

(Source: British Journal of Haematology)

Deciphering the molecular basis of venous thromboembolism: where are we and where should we go?

British Journal of Haematology — Fri, 13 Nov 2009 00:00:00 +0100

Venous thromboembolism (VTE) is a frequent disease that has a major genetic component of risk. However, known identified genetic risk factors account for (Source: British Journal of Haematology)

van de Vosse et al. Antisense-mediated exon skipping to correct IL-12R{beta}1 deficiency in T cells. Blood. 2009;113(19):4548-4555.

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

Allogeneic transplantation for children and adolescents with Hodgkin lymphoma

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

Response: Elevated fibrinogen {gamma}' ratios and clinical outcomes

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

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Elevated fibrinogen {gamma}' ratio is associated with cardiovascular diseases and acute phase reaction but not with clinical outcome

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

Response: NPM1-mutated AML is an entity irrespective of whether or not chromosomal aberrations are present

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

The role of cytogenetic abnormalities in acute myeloid leukemia with NPM1 mutations and no FLT3 internal tandem duplication

Blood — Thu, 12 Nov 2009 17:38:06 +0100

(Source: Blood)

A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis

Blood — Thu, 12 Nov 2009 17:38:06 +0100

In this study, we show that activation of Epac or Rap1 leads to potent inhibition of angiogenesis in vivo. Epac/Rap1 activation down-regulates inhibitor of differentiation 1 (Id1), which negatively regulates thrombospondin-1 (TSP1), an inhibitor of angiogenesis. Consistent with this mechanism, activation of Epac/Rap 1 induces expression of TSP1; conversely, depletion of Epac reduces TSP1 levels in endothelial cells. Blockade of TSP1 binding to its receptor, CD36, rescues inhibition of chemotaxis or angiogenesis by activated Epac/Rap1. Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/Rap1 by inducing Id1 and suppressing TSP1 expression. Finally, TSP1 is also secreted by fibroblasts in response to Epac/Rap...