Summary. The inconsistent ®ndings among association studies that have examined the relationship between factor XIIIA Val34Leu and thrombosis may be owing to (1) population differences in the prevalence of other risk factors that modify the association with Val34Leu, or (2) linkage disequilibrium with other functional factor XIIIA polymorphisms. We therefore performed genotyping for factor XIIIA Val34Leu, Tyr204Phe and Pro564Leu in a population-based study of myocardial infarction (MI) and ischaemic stroke among white women < 45-years of age and 345 demographically similar controls, and examined potential interactions with other risk factors. The presence of the factor XIIIA Leu34 allele was associated with a slight decreased risk of MI [odds ratio (OR) 0á80] that was most pronounced among women with traditional cardiovascular risk factors. Paradoxically, women carrying two copies of the Leu34 allele had a nearly fourfold increased risk of ischaemic stroke relative to the Val34/ Val34 genotype. Heterozygosity for factor XIIIA Phe204 was associated with a milder increased risk of ischaemic stroke, and analysis of a kindred with congenital dys®bri-nogenaemia suggested that co-inheritance of the factor XIIIA Phe204 allele may increase susceptibility to ischaemic stroke. Our results suggest that the factor XIIIA Val34Leu variant may be associated with a decreased risk of MI among young women with other risk factors. The relationship of factor XIIIA polymorphisms to cerebrovascular disease requires further study.

BackgroundThe coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.ObjectivesTo better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.MethodsWe measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters.ResultsVWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.ConclusionsThese data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

This study provides HEA allele frequency and antigen prevalence data in a cohort of Asian and Native Americans donors. Several ethnic groups exhibited differences in HEA frequencies compared to Europeans. Genotype-serotype discrepancies were detected in all systems studied.

This feasibility study provides evidence that centers with primarily Caucasian donors may be able to provide highly antigen-matched products. Knowledge of the GATA status expands the inventory of antigen-matched products. Further work is needed to determine the most clinically appropriate match level for SCD patients.

Background and Purpose-Although family studies have suggested a genetic influence on hemorrhagic stroke, the underlying genetic risk factors remain poorly defined. Coagulation factor XIII, which is involved in hemostasis, fibrinolysis, vascular remodeling, and tissue repair, represents a candidate gene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding-sequence polymorphisms, along with a promoter polymorphism of plasminogen activator inhibitor-1 (PAI-1, which is also involved in fibrin stabilization and vascular remodeling), in young white women with hemorrhagic stroke. Methods-Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and for PAI-1 Ϫ675 4G/5G was performed in a population-based case-control study of 42 white women aged Ͻ45 years with nonfatal hemorrhagic stroke and 345 demographically similar control subjects. Results-Compared with the respective homozygous wild-type genotypes, the Tyr204/Phe204 genotypes (age-adjusted odds ratio [OR] 2.9, 95% 95% CI 1.1 to 7.5) and the Leu564/Leu564 genotype (OR 4.3, 95% CI 1.4 to 13.7) were each associated with an increased risk of nonfatal hemorrhagic stroke. The risk estimate associated with the Phe204 variant was highest in women with subarachnoid hemorrhage and in nonsmokers, whereas the risk estimate of the Leu564/Leu564 genotype was highest in women with intracerebral hemorrhage and in smokers. Women who carried either the Phe204 allele or the Leu564/Leu564 genotype in combination with the PAI-1 5G/5G genotype had a nearly 20-fold increased risk of hemorrhagic stroke (OR 18.9, 95% CI 3.8 to 95.1). Conclusions-Our findings suggest that the Phe204 and Leu564 variants of coagulation factor XIII may be markers for genetic susceptibility to hemorrhagic stroke in women aged Ͻ45 years.