Active von Willebrand factor and the risk of stroke

Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Atherosclerosis (Impact Factor: 3.99). 09/2009; 208(2):322-3. DOI: 10.1016/j.atherosclerosis.2009.07.047
Source: PubMed
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    ABSTRACT: The plasma glycoprotein von Willebrand factor (VWF) exhibits fivefold antigen level variation across the normal human population determined by both genetic and environmental factors. Low levels of VWF are associated with bleeding and elevated levels with increased risk for thrombosis, myocardial infarction, and stroke. To identify additional genetic determinants of VWF antigen levels and to minimize the impact of age and illness-related environmental factors, we performed genome-wide association analysis in two young and healthy cohorts (n = 1,152 and n = 2,310) and identified signals at ABO (P < 7.9E-139) and VWF (P < 5.5E-16), consistent with previous reports. Additionally, linkage analysis based on sibling structure within the cohorts, identified significant signals at chromosome 2q12-2p13 (LOD score 5.3) and at the ABO locus on chromosome 9q34 (LOD score 2.9) that explained 19.2% and 24.5% of the variance in VWF levels, respectively. Given its strong effect, the linkage region on chromosome 2 could harbor a potentially important determinant of bleeding and thrombosis risk. The absence of a chromosome 2 association signal in this or previous association studies suggests a causative gene harboring many genetic variants that are individually rare, but in aggregate common. These results raise the possibility that similar loci could explain a significant portion of the "missing heritability" for other complex genetic traits.
    Proceedings of the National Academy of Sciences 12/2012; 110(2). DOI:10.1073/pnas.1219885110 · 9.67 Impact Factor
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    ABSTRACT: It has been well known for many years that the ABO blood group has a major influence on hemostasis, through its influence on von Willebrand factor and, consequently, factor VIII plasma levels. Although the relationship between non-O blood type and the risk of venous thromboembolism is nowadays also well established, the association with arterial thrombotic events (i.e., myocardial infarction [MI] and ischemic stroke) is less well characterized. To elucidate the latter issue, we have conducted a systematic review and meta-analysis of the existing literature. After an electronic search strategy using MEDLINE and EMBASE and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, 28 studies were finally included in our systematic review. The prevalence of non-O blood group was significantly higher in patients with MI (pooled odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.17-1.40; p < 0.001) and ischemic stroke (pooled OR: 1.17, 95% CI: 1.01-1.35; p = 0.03) than in controls. The restriction of the analysis to high quality studies only confirmed the association with MI (pooled OR: 1.17, 95% CI: 1.03-1.32) but not with ischemic stroke (pooled OR: 1.28, 95% CI: 0.94-1.74). In conclusion, the results of our meta-analysis confirm the existing literature evidence of a weak association between non-O blood group and vascular arterial thrombosis, in particular myocardial ischemia.
    Seminars in Thrombosis and Hemostasis 12/2013; 40(1). DOI:10.1055/s-0033-1363460 · 3.88 Impact Factor
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    ABSTRACT: Von Willebrand Factor (VWF) plays an important role in hemostasis by mediating platelet adhesion and aggregation. Ultralarge VWF multimers are cleaved by ADAMTS13 in smaller, less procoagulant forms. An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been observed between low ADAMTS13 levels and arterial thrombosis. We reviewed the current literature and performed meta-analyses on the relationship between both VWF and ADAMTS13 with arterial thrombosis. Most studies showed an association between high VWF levels and arterial thrombosis. It remains unclear whether ADAMTS13 is a causal independent risk factor because the association between low ADAMTS13 and arterial thrombosis is so far only shown in case-control studies. Prospective studies are awaited. A causal role for ADAMTS13 is supported by mice studies of cerebral infarction where the infusion of recombinant human ADAMTS13 reduced the infarct size.
    Blood reviews 04/2014; 28(4). DOI:10.1016/j.blre.2014.04.003 · 5.57 Impact Factor