Fibrinogen γ' levels in patients with intracerebral hemorrhage.

BACKGROUND: The fibrinogen γ' variant (γ') has both antithrombotic and prothrombotic properties when compared to normal fibrinogen. It may therefore be of relevance in intracerebral hemorrhage and intraventricular extension of the bleeding. OBJECTIVE: To study the role of γ' in intracerebral hemorrhage, and in intraventricular extension of the hemorrhage. PATIENTS/METHODS: We performed a case-control study in 156 controls and 55 patients with intracerebral hemorrhage, with and without intraventricular extension. Levels of fibrinogen γ' and the γ'/total fibrinogen ratio were measured in all participants. RESULTS: Levels of γ' were increased in patients with intracerebral hemorrhage when compared with controls (0.40 vs 0.32g/l, p<0.001). The γ'/total fibrinogen ratio was similar in patients and controls (0.092 vs 0.096 p=0.42). There was evidence for an unfavorable outcome in patients with fibrinogen levels in the highest tertile compared with the lowest tertile (OR 4.0, 95%CI 1.1-15.2), and a nonsignificant trend toward unfavorable outcome with higher levels of γ' (p-value for trend=0.06). CONCLUSIONS: Our study shows that absolute levels of fibrinogen γ' are increased in patients with intracerebral hemorrhage, but relative levels are similar in patients and controls, suggesting that the absolute rise in γ' is an acute phase response.

Haplotypes of the fibrinogen gene and cerebral small vessel disease: the Rotterdam scan study.

OBJECTIVE: Fibrinogen levels and fibrinogen clot structure have been implicated in the pathogenesis of vascular disease. We examined fibrinogen levels and variation in fibrinogen genes (fibrinogen gamma (FGG), alpha (FGA) and beta (FGB)), which have been associated with fibrin clot structure and fibrinogen levels, in relation to cerebral small vessel disease (SVD). METHODS AND RESULTS: This study was performed as part of the Rotterdam Scan Study, a population based study in 1077 elderly patients undergoing cerebral MRI. Plasma fibrinogen levels and haplotypes were determined. We examined the association between fibrinogen levels and haplotype with silent brain infarcts and white matter lesions using logistic regression models. We constructed seven haplotypes (frequency >0.01) that describe the total common variation in the FGG and FGA genes. Haplotype 2 (GATAGTG) was associated with the presence of silent brain infarcts compared with the most frequent haplotype (GGTGGTA) (OR 1.41, 95% CI 1.03 to 1.94). Haplotype 3 (GGCGATA) was associated with periventricular white matter lesions in the highest tertile of the distribution (OR 1.40, 95% CI 1.01 to 1.92). No association was found between plasma fibrinogen levels and SVD. CONCLUSIONS: Our study provides evidence for an association of common variation in the FGG and FGA genes with cerebral SVD. It is possible that the structure of the fibrin clot rather than plasma fibrinogen levels plays a role in the pathogenesis of cerebral SVD.