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Advances in Understanding "High on-Treatment Platelet Reactivity".email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19888510 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Hayward CP Tags: Thromb Haemost Source Type: journals

Heparin and its derivatives - Present and future.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19888511 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Harenberg J, Casu B Tags: Thromb Haemost Source Type: journals

From heparin to EP217609: The long way to a new pentasaccharide-based neutralisable anticoagulant with an unprecedented pharmacological profile.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The elucidation of the structure of the antithrombin binding sequence in heparin has given a large impulse to the rational design of heparin related drugs. De novo chemical synthesis of the corresponding pentasaccharide as well as simplified analogues has provided very specific, antithrombin-mediated inhibitors of factor Xa with various pharmacokinetic profiles. Fondaparinux and idraparinux are examples of such compounds that have found clinical application as antithrombotics. Because of the very specific binding to antithrombin the pharmacokinetics of pentasaccharides can be predicted and transferred to other molecule...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Petitou M, Nancy-Portebois V, Dubreucq G, Motte V, Meuleman D, de Kort M, van Boeckel CA, Vogel GM, Wisse JA Tags: Thromb Haemost Source Type: journals

Development of idraparinux and idrabiotaparinux for anticoagulant therapy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Idraparinux is an analogue of fondaparinux binding with high affinity to antithrombin. It was designed for weekly, rather than daily, administration, with an exceptionally long half-life. One potential problem with small heparin-like fragments of this type is the difficulty of neutralising excessive activity in the case of side-effects or overdose. The efficacy of idraparinux was was proven in clincial studies with patients suffering from venous thromboembolism (VTE) or atrial fibrillation. Due to major bleeding events during treatment for more than six months the development of idraparinux was stopped. Idrabiotaparinu...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Harenberg J Tags: Thromb Haemost Source Type: journals

Binding between heparin and the integrin VLA-4.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Heparin possesses antimetastatic effects that were related to various molecular mechanisms beyond anticoagulant activities. The ability of heparin to interfere with the function of adhesion receptors in the metastatic course appears as a promising therapeutic approach. This refers to numerous findings that heparin attenuates metastasis in a selectin-dependent manner. We recently demonstrated that heparin interferes with the integrin VLA-4 on murine melanoma cells binding to VCAM-1. To confirm this activity and to obtain further insight into molecular recognition of heparin by VLA-4, we investigated the inhibition of VL...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Schlesinger M, Simonis D, Schmitz P, Fritzsche J, Bendas G Tags: Thromb Haemost Source Type: journals

Heparin, heparan sulfate and heparanase in inflammatory reactions.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Heparan sulfate (HS) proteoglycans at the cell surface and in the extracellular matrix of most animal tissues are essential in development and homeostasis, and are implicated in disease processes. Emerging evidence demonstrates the important roles of HS in inflammatory reactions, particularly in the regulation of leukocyte extravasation. Heparin, a classical anticoagulant, exhibits anti-inflammatory effects in animal models and in the clinic, presumably through interference with the functions of HS, as both polysaccharides share a high similarity in molecular structure. Apart of regulation during biosynthesis, the stru...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Li JP, Vlodavsky I Tags: Thromb Haemost Source Type: journals

Effects of polysaccharides enriched in 2,4-disulfated fucose units on coagulation, thrombosis and bleeding. Practical and conceptual implications.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, the location of 2,4-disulfated fucose units in the polysaccharide chains dictates the effects on coagulation, thrombosis and bleeding. PMID: 19888516 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Fonseca RJ, Santos GR, Mourão PA Tags: Thromb Haemost Source Type: journals

Effects of a semi-synthetic N-,O-sulfated glycosaminoglycan K5 polysaccharide derivative in a rat model of cerebral ischaemia/reperfusion injury.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, the results demonstrated that the sulfated semi-synthetic K5 derivative K5-N,OSepi protects the brain against I/R injury by disrupting multiple levels of the apoptotic and inflammatory cascade, including inhibition of NF-kappaB activation. PMID: 19888517 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Collino M, Castiglia S, Manoni M, Salsini L, Chini J, Masini E, Fantozzi R Tags: Thromb Haemost Source Type: journals

Heparins: Process-related physico-chemical and compositional characteristics, fingerprints and impurities.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
During the past 25 years, heparin extraction and purification processes have changed. The results of these changes are reflected by the continuous increase in potency of the International Standard for heparin. This increase is due not only to a higher purity, but also to a number of changes in the physico-chemical characteristics of heparin. For long time, all these changes have been disregarded as non-critical by regulatory authorities. Heparin marketing authorisation was reviewed only two years ago and Pharmacopoeia monographs were reviewed just for the addition of new tests, mainly aimed at tackling the oversulfated...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Liverani L, Mascellani G, Spelta F Tags: Thromb Haemost Source Type: journals

From crisis to opportunity: A perspective on the heparin crisis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19888519 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Sasisekharan R, Shriver Z Tags: Thromb Haemost Source Type: journals

Detection and neutralisation of heparin by a fluorescent ruthenium compound.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We describe here a new optical molecular probe for the detection of LMWH in serum samples. The polycationic ruthenium compound 1 is applicable to the quantification of heparin by monitoring 630 nm fluorescence. In addition, compound 1 is a rare example of a non-polymeric low molecular weight compound which neutralises the anticoagulant activity of heparin and LMWH in plasma samples. Limitation of the method is its low sensitivity currently being improved by structural modification of compound 1. PMID: 19888520 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Szelke H, Harenberg J, Krämer R Tags: Thromb Haemost Source Type: journals

Structural features of low-molecular-weight heparins affecting their affinity to antithrombin.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This study is therefore critical for establishing correlations between structural features of LMWHs and their AT-mediated anticoagulant activity. PMID: 19888521 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G Tags: Thromb Haemost Source Type: journals

The potential for circular dichroism as an additional facile and sensitive method of monitoring low-molecular-weight heparins and heparinoids.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The ultraviolet circular dichroism (CD) spectra of commercial low-molecular-weight heparins, heparinoids and other anticoagulant preparations have been recorded between 180 and 260 nm. Principal component analysis of the spectra allowed their differentiation into a number of groups related to the means of their production reflecting the structural changes introduced by each process. The findings suggest that CD provides a complementary technique for the rapid analysis of heparin preparations. PMID: 19888522 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Rudd TR, Skidmore MA, E Guimond S, Holman J, Turnbull JE, Lauder RM, Fernig DG, Yates EA Tags: Thromb Haemost Source Type: journals

Activated partial thromboplastin time monitoring in patients receiving unfractionated heparin for venous thromboembolism in relation to clinical outcomes.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, weight-adjusted subcutaneous unfractionated heparin without anticoagulation monitoring may be feasible for patients with acute venous thromboembolism. No differences exist between intravenous and subcutaneous modes of administration with regards to the correlation between anticoagulant measures and the clinical outcomes. More research is needed to substantiate this observation. PMID: 19888523 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Vardi M, Laor A, Bitterman H Tags: Thromb Haemost Source Type: journals

Heparin-induced thrombocytopenia (HIT II) - A drug-associated autoimmune disease.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Autoimmune thrombocytopenia (ITP) is an acquired autoimmune disease characterised by isolated persistent thrombocytopenia and normal megakaryopoiesis. This definition also applies to heparin-induced thrombocytopenia (HIT II), a frequent side effect of heparin treatment. In HIT II, the immunogen is a coagulation active complex of heparin and platelet factor 4 (PF4). By now, diagnostics of HIT II is often material and time consuming. Three groups of patients were investigated for HIT II antibodies (HIT II-AB): 54 hospitalised stroke patients, 87 hospitalised cardiac patients, and 71 patients on chronic haemodialysis, all...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Nowak G Tags: Thromb Haemost Source Type: journals

Direct inhibitors of coagulation proteins - the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Heparins, either unfractionated or low-molecular-weight (UFH and LMWHs), and vitamin K antagonists (VKAs) are currently the anticoagulants of choice for the prevention of post-operative venous thromboembolism (VTE) and for the treatment of acute venous and arterial thromboembolism. While VKAs are widely used in the US, LMWHs are the standard of care in the EU. Although efficacious, these agents are associated with a number of drawbacks, such as the risk of heparin-induced thrombocytopenia, the need for frequent coagulation monitoring in the case of UFH and VKAs, and the parenteral mode of administration in the case of ...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Laux V, Perzborn E, Heitmeier S, von Degenfeld G, Dittrich-Wengenroth E, Buchmüller A, Gerdes C, Misselwitz F Tags: Thromb Haemost Source Type: journals

M118 - A rationally engineered low-molecular-weight heparin designed specifically for the treatment of acute coronary syndromes.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We describe here M118, a novel LMWH designed specifically for use in the treatment of ACS. M118 shows broad anticoagulant activity, including potent activity against both factor Xa (~240 IU/mg) and thrombin (factor IIa; ~170 IU/mg), low polydispersity, high (78%) subcutaneous bioavailability in rabbits, and predictable subcutaneous and intravenous pharmacokinetics. Additionally, the anticoagulant activity of M118 is monitorable by standard coagulation assays and is reversible with protamine. M118 demonstrates superior activity to conventional LMWH in a rabbit model of abdominal arterial thrombosis without increasing bleedi...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Kishimoto TK, Qi YW, Long A, Capila I, Sasisekharan R, Guerrero L, Fier I, Roach J, Venkataraman G Tags: Thromb Haemost Source Type: journals

The tainted heparin story: an update.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Recently, certain batches of heparin have been associated with an acute, rapid onset of serious side-effects indicative of allergic-type reactions. These reports generated significant concern regarding the possible presence of a dangerous contaminant within heparin and highlighted the need to re-assess the purity criteria of heparin preparations for clinical use. Given the nature of the array of all possible contaminants, traditional screening tests cannot safely differentiate between contaminated and uncontaminated heparin preparations. Mono- and bi-dimensional NMR spectroscopy are powerful techniques that are able to...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Guerrini M, Shriver Z, Bisio A, Naggi A, Casu B, Sasisekharan R, Torri G Tags: Thromb Haemost Source Type: journals

Pro: "Anti-platelet therapy is an alternative to oral anticoagulation for atrial fibrillation".email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19888528 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Healey JS Tags: Thromb Haemost Source Type: journals

Contra: "Anti-platelet therapy is an alternative to oral anticoagulation for atrial fibrillation".email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19888529 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Apostolakis S, Shantsila E, Lip GY, Lane DA Tags: Thromb Haemost Source Type: journals

The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Although, the main physiological role of monocytes is attributed to innate immunity (that is, phagocytosis) and the development of tissue macrophages and dendritic cells, the pathophysiological role of these goes far behind these (simplistic) limits. Indeed, monocytes constitute a major source of blood tissue factor, a key element of the extrinsic coagulation cascade. Monocytes actively bind to platelets, thus forming very prothrombotic monocyte-platelet aggregates. Additionally, these cells link inflammation and the procoagulant state observed in various prothrombotic conditions. However, monocytes are also crucial fo...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Shantsila E, Lip GY Tags: Thromb Haemost Source Type: journals

Factor VIII-eGFP fusion proteins with preserved functional activity for the analysis of the early secretory pathway of factor VIII.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Considering the difficulty in detecting factor (F)VIII in vivo, fluorescently labelled FVIII protein provides a tool to analyse the intracellular localisation, bio distribution, and pharmacokinetics of the protein in living organisms. Here, we report the use of FVIII full length and B-domain deleted proteins, fused to enhanced green fluorescent protein (eGFP) at the C-terminus of the coagulation protein via a nine amino acid spanning linker. Comparison of the FVIII-eGFP fusion proteins to their unlabelled counterparts showed no impairment with respect to recombinant expression levels, intracellular processing, specific...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Heinz S, Schüttrumpf J, Simpson JC, Pepperkok R, Nicolaes GA, Abriss D, Milanov P, Roth S, Seifried E, Tonn T Tags: Thromb Haemost Source Type: journals

Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, CAT conditions differentially affected the sensitivity of thrombin generation to elevated factor levels. Monitoring the peak height and/or ETP following initiation of clotting in PFP with 1 pM TF was most likely to detect hypercoagulability due to increased procoagulant factor levels. PMID: 19888532 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Machlus KR, Colby EA, Wu JR, Koch GG, Key NS, Wolberg AS Tags: Thromb Haemost Source Type: journals

Impact of long-term testosterone treatment on plasma levels of free TFPI and TF-induced thrombin generation ex vivo in elderly men with low testosterone levels.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, normalising testosterone levels by testosterone treatment for 12 months in elderly men did not affect TF-induced coagulation or plasma TFPI levels. The potential antithrombotic role of testosterone therapy remains to be elucidated. PMID: 19888533 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Agledahl I, Brodin E, Svartberg J, Hansen JB Tags: Thromb Haemost Source Type: journals

Rates of venous thromboembolism occurrence in medical patients among the insured population.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, commercially insured medical patients in the US are at high risk of VTE following hospital discharge. One-quarter of medical patients who developed a VTE are at high risk of developing the more severe form of the disease, namely PE, with independent predictors of VTE in the post-discharge period including previous VTE and cancer. PMID: 19888534 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Spyropoulos AC, Hussein M, Lin J, Battleman D Tags: Thromb Haemost Source Type: journals

Effect of sex difference on platelet adhesion, spreading and aggregate formation under flow.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, our data would argue against an intrinsic difference for female mouse platelets in regulating the major functional platelet responses: platelet adhesion, spreading, or aggregation under flow. PMID: 19888535 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Eshel-Green T, Berny MA, Conley RB, McCarty OJ Tags: Thromb Haemost Source Type: journals

Cellular prion protein in blood platelets associates with both lipid rafts and the cytoskeleton.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The recently shown transmissibility of variant Creutzfeldt-Jakob disease (vCJD) by blood transfusion emphasises the need for better understanding of the cellular prion protein (PrPc) in blood. A substantial amount of cell-associated PrPc in blood resides in platelets. Platelet activation leads to up-regulation of PrPc on the platelet surface and its release on exosomes and microparticles. The sub-cellular localisation and function of platelet PrPc, however, is poorly understood. In the present study, we investigated the association of PrPc with platelet lipid rafts and the platelet cytoskeleton. Immuno-fluorescence mic...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Brouckova A, Holada K Tags: Thromb Haemost Source Type: journals

Variable effects of alpha v suppression on VEGFR-2 expression in endothelial cells of different vascular beds.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, we determined the effect of alphavbeta3 and alphavbeta5 suppression in endothelial cells (EC) on vascular endothelial growth factor (VEGF) and VEGFR-2 expression. alphav was suppressed by shRNA in HUVEC (venous endothelial cells) and HMVEC (microvascular endothelial cells). VEGFR-2 was significantly upregulated by alphav suppression in HUVEC and downregulated in HMVEC at both mRNA and protein levels, as assessed by real-time PCR and flow cytometry, respectively. HMVEC displayed completely abolished Sp1 binding to the VEGFR-2 promoter, and HUVEC exhibited enhanced binding to the -170 E-Box element in the VEGF...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Dardik R, Livnat T, Seligsohn U Tags: Thromb Haemost Source Type: journals

Constriction of carotid arteries by urokinase-type plasminogen activator requires catalytic activity and is independent of NH(2)-terminal domains.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Urokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle - not the catalytic - domain of uPA. We used an in-vivo uPA overexpression model to test the hypothesis that uPA-induced vasoconstriction is a reversible vasomotor process that can be prevented - and uPA fibrinolytic activity preserved - by: 1) removing the growth factor...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Massey PG, Tanaka S, Buckler JM, Jiang B, McCourtie A, Qian K, Tom C, Stempien-Otero A, Wen S, Luttrell I, Chitaley K, Dichek DA Tags: Thromb Haemost Source Type: journals

Short-term ethinylestradiol treatment suppresses inferior caval vein thrombosis in obese mice.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Obesity and oral estrogens are independent risk factors for venous thrombosis, and their combined effect is stronger than the sum of the isolated factors. It was the objective of this study to investigate the interaction between obesity and estrogens at the level of venous thrombotic tendency, coagulation and inflammation in a mouse model. Female C57Bl/6J mice were fed a standard fat diet (SFD) or a high fat diet (HFD) to induce nutritional obesity. After 14 weeks, while maintaining their diet, mice were orally treated eight days with 1 microg ethinylestradiol or vehicle (n=25 per group), and subsequently subjected to ...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Cleuren AC, van Hoef B, Hoylaerts MF, van Vlijmen BJ, Lijnen HR Tags: Thromb Haemost Source Type: journals

Heptest-STAT, a new assay for monitoring of low-molecular-weight heparins, is not influenced by pregnancy-related changes of blood plasma.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Monitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptest-STAT is a new clotting assay for monitoring of LMWHs, which has been optimised for use in near-patient laboratory instrumentation. It has been suggested that monitoring of LMWHs requires the use of individual calibration curves for each LMWH. We compared the dose response of four conventional LMWHs and f...
Source: Thrombosis and Haemostasis - November 1, 2009 Category: Hematology Authors: Dempfle CE, Zharkowa U, Elmas E, Ahmad-Nejad P, Neumaier M, Borggrefe M Tags: Thromb Haemost Source Type: journals

Does weather influence the development of deep venous thrombosis? The answer may be blowing in the wind.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19806243 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Reid JH Tags: Thromb Haemost Source Type: journals

Platelets interact with bacterial pathogens.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19806244 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Shannon O Tags: Thromb Haemost Source Type: journals

C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, this prospective, population-based study suggests elevated CRP is independently associated with increased risk of VTE. PMID: 19806245 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Folsom AR, Lutsey PL, Astor BC, Cushman M Tags: Thromb Haemost Source Type: journals

Risk factors for cerebral venous thrombosis and deep venous thrombosis in patients aged between 15 and 50 years.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This study demonstrated no differences in thrombophilic markers between CVT patients and DVT/PE patients aged between 15 and 50 years, while the frequency of some transient risk factors was different. Cerebral venous thrombosis was relatively more common in women and hormonal factors may predispose to CVT compared to DVT/PE, while trauma, immobilisation and surgery may be less important in the pathophysiology of CVT. PMID: 19806246 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Koopman K, Uyttenboogaart M, Vroomen PC, van der Meer J, De Keyser J, Luijckx GJ Tags: Thromb Haemost Source Type: journals

Differences in prethrombin-1 activation with human or bovine factor Va can be attributed to the heavy chain.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Human and bovine factor Va (FVa) function similarly in the activation of prothrombin but differently in the activation of prethrombin-1 (Pre-1). Pre-1 activation with human FVa proceeds at about 22 percent of the rate with bovine FVa. The dependencies of initial rates on the FVa and Pre-1 concentrations indicate that the differential activity is expressed in kcat differences, rather than differences in the assembly of prothrombinase or the K(m) value of the substrate. The heavy and light chains of both species of FVa were separated and interspecies hybrids were constructed in the presence of Ca(++). Studies of the acti...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Kim PY, Manuel R, Nesheim ME Tags: Thromb Haemost Source Type: journals

Genetic fusion to albumin improves the pharmacokinetic properties of factor IX.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Haemophilia B is a X-chromosome linked disease characterised by a deficiency of functionally active coagulation Factor IX (FIX). Patients with severe haemophilia B at risk of recurrent bleeding are treated approximately twice a week in a prophylactic setting by application of FIX concentrates. To increase convenience and compliance of the therapy it is desirable to reduce the dosing frequency by improving the pharmacokinetic properties of FIX. Here a concept of rFIX (recombinant factor IX) albumin fusion proteins (rIX-FPs) with cleavable linker peptides derived from the FIX activation sequence is presented. Constructs ...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Metzner HJ, Weimer T, Kronthaler U, Lang W, Schulte S Tags: Thromb Haemost Source Type: journals

Identification of a protein S-interactive site within the A2 domain of the factor VIII heavy chain.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We have recently demonstrated that protein S impairs the intrinsic tenase complex, independent of activated protein C, in competitive interactions between the A2 and A3 domains of factor VIIIa and factor IXa. In the present study, we have identified a protein S-interactive site in the A2 domain of factor VIIIa. Anti-A2 monoclonal antibody recognising a factor IXa-functional region (residues 484-509) on A2, and synthetic peptide inhibited the A2 binding to protein S by ~60% and ~70%, respectively, in solid-phase binding assays. The 484-509 peptide directly bound to protein S dose-dependently. Covalent cross-linking was ...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Takeyama M, Nogami K, Saenko EL, Nishiya K, Ogiwara K, Shima M Tags: Thromb Haemost Source Type: journals

The A6936G polymorphism of the endothelial protein C receptor gene is associated with the risk of unexplained foetal loss in Mediterranean European couples.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The endothelial protein C receptor (EPCR) is expressed by trophoblast cells. Mid-gestation pregnancy loss is described in animals with a haemochorial placenta lacking EPCR. The A6936G allele of the EPCR gene (PROCR) may be associated with lower EPCR densities on trophoblasts, but data are lacking for its effect on the risk of pregnancy loss in humans. A 1:2 case-control study on unexplained pregnancy loss was nested in the NOHA First cohort: 3,218 case couples and 6,436 control couples were studied for PROCR A6936G, coagulation factor V gene (F5) G1691A and coagulation factor II gene (F2) G20210A polymorphisms. Ethnici...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Cochery-Nouvellon E, Chauleur C, Demattei C, Mercier E, Fabbro-Peray P, Marès P, Mismetti P, Lissalde-Lavigne G, Gris JC Tags: Thromb Haemost Source Type: journals

Cardiovascular risk factors in idiopathic compared to risk-associated venous thromboembolism: A focus on fibrinogen, factor VIII, and high-sensitivity C-reactive protein (hs-CRP).email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
There have recently been reports of an increased incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism (VTE) compared to patients with risk-associated VTE. The aim of our study was to evaluate whether elevated clotting factors, which have been linked to chronic sub-clinical inflammation and arterial thromboembolic disease, have a higher prevalence in idiopathic VTE compared to secondary VTE. Plasma fibrinogen, factor VIII, and high-sensitivity C-reactive protein (hs-CRP) levels were determined in a cohort of sex- and age-matched patients with unprovoked VTE (n=101), patients wit...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Luxembourg B, Schmitt J, Humpich M, Glowatzki M, Dressler D, Seifried E, Lindhoff-Last E Tags: Thromb Haemost Source Type: journals

The influence of meteorological variables on the development of deep venous thrombosis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The influence of weather on deep venous thrombosis (DVT) incidence remains controversial. We aimed to characterize the temporal association between DVT and meteorological variables including atmospheric pressure. Data relating to hospital admissions with DVT in Scotland were collected retrospectively for a 20 year period for which corresponding meteorological recordings were available. Weather variables were calculated as weighted daily averages to adjust for variations in population density. Seasonal variation in DVT and short-term effects of weather variables on the relative risk of developing DVT were assess using P...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Brown HK, Simpson AJ, Murchison JT Tags: Thromb Haemost Source Type: journals

Risk stratification of patients with pulmonary embolism based on pulse rate and D-dimer concentration.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
To enable outpatient treatment of a selected group of patients with pulmonary embolism (PE), insight in the determinants of adverse clinical outcome is warranted. We have identified risk factors for serious adverse events (SAE) within the first 10 days of acute PE. We have retrospectively analysed data of 440 consecutive patients with acute PE. Collected data included age, gender, medical history, blood pressure, pulse rate and D-dimer concentration. The variables associated with SAE in the first 10 days in univariate analysis (p<0.15) have been included in a multivariate logistic regression model (backward conditio...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Agterof MJ, van Bladel ER, Schutgens RE, Snijder RJ, Tromp EA, Prins MH, Biesma DH Tags: Thromb Haemost Source Type: journals

Long-term complications of medical patients with hospital-acquired venous thromboembolism.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, hospitalised medical patients are particularly vulnerable to the development of recurrent VTE, PTS, and CTEPH. These VTE complications would be reduced by more than half with universal thromboprophylaxis. Further efforts should focus on improving VTE prophylaxis utilisation. PMID: 19806254 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Fanikos J, Piazza G, Zayaruzny M, Goldhaber SZ Tags: Thromb Haemost Source Type: journals

alpha(1)-acid glycoprotein (AGP)-induced platelet shape change involves the Rho/Rho kinase signalling pathway.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
alpha(1)-acid glycoprotein (AGP) is an acute-phase protein that contributes to inflammation processes. The role of AGP in platelet activation and thrombosis is, however, largely unknown. Therefore, we thoroughly investigated the effects of AGP on human platelets. Platelets were isolated from healthy volunteers and subsequently exposed to AGP. Platelet responses were monitored as change in light transmission, intracellular calcium concentration, light microscopy and protein phosphorylation by Western blot. We found that AGP induced platelet shape change independently of a second release of adenine nucleotides or thrombo...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Gunnarsson P, Levander L, Påhlsson P, Grenegård M Tags: Thromb Haemost Source Type: journals

The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, activated platelets release significant amounts of APRIL in a long-lasting manner, differently regulated than the gradual release of other platelet-derived TNF superfamily ligands. The enhanced expression of APRIL in atherosclerotic disorders, both systemically and within the lesion, may suggest a potential involvement of APRIL in atherogenesis. PMID: 19806256 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Sandberg WJ, Otterdal K, Gullestad L, Halvorsen B, Ragnarsson A, Frøland SS, Damås JK, Oie E, Aukrust P, Hansson GK, Yndestad A Tags: Thromb Haemost Source Type: journals

Proteomic and functional characterisation of platelet microparticle size classes.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Activated platelets release large lipid-protein complexes termed microparticles. These platelet microparticles (PMP) are composed of vesicular fragments of the plasma membrane and alpha-granules. PMP facilitate coagulation, promote platelet and leukocyte adhesion to the subendothelial matrix, support angiogenesis and stimulate vascular smooth muscle proliferation. Objectives: PMP were separated into 4 size classes to facilitate identification of active protein and lipid components. PMP were obtained from activated human platelets and separated into 4 size classes by gel filtration chromatography. Proteins were identifi...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Dean WL, Lee MJ, Cummins TD, Schultz DJ, Powell DW Tags: Thromb Haemost Source Type: journals

The influence of clinical characteristics, laboratory and inflammatory markers on 'high on-treatment platelet reactivity' as measured with different platelet function tests.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are independently associated with an increased risk of atherothrombotic events. However, despite this positive correlation, the definitions of both HCPR and HAPR vary largely throughout studies and between different platelet function assays. The aim of the present study was to explore clinical and laboratory parameters that are associated with HCPR and HAPR as measured with different platelet function tests. 530 clopidogrel and aspirin pre-treated patients undergoing elective PCI (percutaneous coronary intervention) were enrol...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Elsenberg EH, van Werkum JW, van de Wal RM, Zomer AC, Bouman HJ, Verheugt FW, Berg JM, Hackeng CM Tags: Thromb Haemost Source Type: journals

Tissue factor activity of blood mononuclear cells is increased after total knee arthroplasty.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Tissue factor (TF) is present in small quantities in normal blood and is reported to be elevated in arterial and venous thrombosis. Patients undergoing total knee arthoplasty (TKA) are at high risk of post-operative venous thromboembolism (VTE). To evaluate the possible contribution of elevated blood TF to VTE risk, we performed serial studies of peripheral blood mononuclear cell (PBMC) functional TF procoagulant activity (PCA) in 19 patients after TKA. PBMC and platelet TF PCA were measured by a functional, clot-based assay following decryption with a calcium ionophore. Plasma TF antigen levels were measured by ELISA....
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Johnson GJ, Leis LA, Bach RR Tags: Thromb Haemost Source Type: journals

Pneumococcal association to platelets is mediated by soluble fibrin and supported by thrombospondin-1.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Platelets and coagulation are involved in bacterial colonisation of the host. Streptocococcus pneumoniae (pneumococcus) are important etiologic agents of respiratory tract infections in humans. The formation of pneumococci-platelet associations may facilitate haematogenous dissemination of pneumococci by providing an adhesive surface on damaged endothelium. However, the formation of platelet-pneumococci associations and the factors involved in this process have not been described so far. The formation of platelet-pneumococci associates was analysed and quantified using flow cytometry. Binding of pneumococci to platelet...
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Niemann S, Kehrel BE, Heilmann C, Rennemeier C, Peters G, Hammerschmidt S Tags: Thromb Haemost Source Type: journals

Proliferative stimulation of the vascular endothelin-1 axis in vitro and ex vivo by infection with Chlamydia pneumoniae.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, this is the first study to demonstrate infection to dysregulate the ET-1 axis towards inducing a proatherogenic proliferative phenotype. PMID: 19806261 [PubMed - in process] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - September 30, 2009 Category: Hematology Authors: Kern JM, Maass V, Rupp J, Maass M Tags: Thromb Haemost Source Type: journals