Objective-The beneficial effect of dietary fish oil, rich in omega-3 polyunsaturated fatty acids (PUFAs), on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action. We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein. Methods and Results-Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks. Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation, as well as plasma levels of fibrinogen and factor V, but had no effect on vitamin K-dependent coagulation factors. Before fish oil intake, thrombin generation (reflecting the coagulant potential) considerably varied between plasmas from individual subjects, which were partly explained by variation in prothrombin, antithrombin, fibrinogen, and factor V levels. Fish oil intake reduced thrombin generation in the presence and absence of platelets. This reduction correlated with the fish oil effect on fibrinogen and factor V levels. Interestingly, the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen ␣-chain polymorphism. Conclusions-Dietary omega-3 PUFAs provoke a hypocoagulant, vitamin K-independent effect in humans, the degree of which may depend on fibrinogen level. Key Words: coagulation Ⅲ factor V Ⅲ fibrinogen Ⅲ fish oil Ⅲ thrombin generation S ince the 1970s, fish oil has been studied as a nutritional component with antithrombotic potential. 1 The protective effect on thrombosis has been attributed to the omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid, which are abundantly present in fish oil. Early epidemiological and intervention studies pointed to a strong association between consumption of omega-3 PUFAs and a reduced risk of coronary heart disease, even with only 2 fish dishes per week. 2,3 Currently, a daily intake of 0.3 g of omega-3 PUFAs is recommended for healthy adults, and a daily dose up to 1 to 3 g is recommended for patients with coronary heart disease or hypertriglyceridemia. 4 Despite 30 years of study, the precise mechanisms of action of omega-3 PUFAs are still a matter of debate. 5 Established effects include an altered heart and vessel function, a decreased risk for arrhythmias, and lowering of blood pressure. Many reports also describe effects on plasma hemostatic variables, but usually with high interstudy variation. Best documented is that omega-3 PUFA intake reduces plasma triglycerides levels, whereas plasma cholesterol is decreased in only few studies. 6 -8 Part of published studies show, often mild, lowering effects of omega-3 PUFA on platelet activation and bleeding time. 9 With respect to coagulation, some trials point to a moderate reduction by fish oil of the plasma levels of fibrinogen and coagulation factors V, VII, and X, 10 -12 whereas other studies fail to detect this. 5,9 Because some of these factors require vitami...

Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic hematopoietic stem cell transplantation (SCT). The effect of NOD2/CARD15 polymorphism is reported to be associated with type of donor (sibling or matched unrelated donor) as well as type of conditioning regimen. We reviewed NOD2/CARD15 SNPs in all donor/recipient pairs of 192 consecutive patients who received nonmyeloablative allogeneic SCT at our institution between 2002 and 2006. All patients were treated with fludarabine 30 mg/m(2)/day for 3 days followed by 200 cGy total-body irradiation (TBI) (n = 154) or TBI alone (n = 38) and received grafts from HLA-matched related (n = 132) or unrelated (n = 61) donors. NOD2/CARD15 polymorphisms were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. The incidences of acute and chronic graft-versus-host disease (aGVHD, cGVHD) were 39% and 49%, respectively, in patients with NOD2/CARD15 variants versus 51% and 61% in patients with wild type. The relapse rate at 3 years was 38% in patients with variants and 36% in patients with wild type. The incidence of transplant-related mortality was 22% for patients with variants and 21% for patients with wild type. Overall survival (OS) at 3 years was 56% in patients with variants and 64% in patients with wild-type NOD2/CARD15. There was no significant impact of NOD2/CARD15 mutations on clinical outcome (all P > .05, Kaplan-Meier and Fine and Gray's tests). These data indicate that mutations in the NOD2/CARD15 gene are not a risk factor for clinical outcome in nonmyeloablative allogeneic SCT. Therefore, screening for NOD2/CARD15 polymorphisms in patients or donors does not have additional value in patients undergoing nonmyeloablative SCT.

An association between human leukocyte antigen (HLA) molecules and the incidence of various diseases has been recognized for years. Molecules of the HLA system also exert an important role on the clinical outcome after transplantation such as stem cell transplantation. The conventional HLA typing method is sequence based typing (SBT) which is reliable but laborious. The goal of this study was to develop a high-throughput Taqman assay to screen large panels for HLA-E alleles. Two functional HLA-E alleles, *0101 and *0103, have been identified. We set up the Taqman assay with genomic DNA as template to discriminate the three HLA-E genotypes: homozygous HLA-E*0101, heterozygous *0101, *0103 and homozygous *0103. This Taqman approach was validated by the comparison of results obtained with the typing results acquired by sequenced base typing (SBT). Additional screening of a large panel showed the pronounced discriminative capacity of the Taqman assay for HLA-E allele typing. The Taqman assay is a fast, reliable and consistent HLA-E allele typing method, especially useful to screen large panels.

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