The role of fibrinogen variants in cardiovascular diseases and wound healing

Maintaining the integrity and patency of the vascular system is essential for the viability of humans. When vascular injury has occurred, fast formation of a thrombus at the site of injury is essential to seal the wound, resulting in haemostasis. Haemostasis is a tightly regulated process, which involves the activation of endothelial cells, platelets, procoagulants and the inhibition of fibrinolytic factors. Haemostasis can be separated in two phases called primary and secondary haemostasis, which occur simultaneously.1 In primary haemostasis, a platelets plug is rapidly formed at the site of injury, whereas in secondary haemostasis, blood coagulation is initiated, either with negatively charged surfaces (intrinsic pathway) or with tissue factor (extrinsic pathway). The cascade leads to the generation of thrombin and the formation of a fibrin network.2 The thrombus provides an effective restriction for bleeding. Hence, an imbalance of normal haemostasis caused by pathologic disorders may lead to thrombosis or hemorrhage, which may account for morbidity and mortality. Fibrinogen is a central protein in the hemostatic system. At the final stage of the blood coagulation system, thrombin converts the soluble fibrinogen into fibrin monomers, which then polymerize to an insoluble fibrin clot. Furthermore, fibrinogen induces platelet adhesion and aggregation via the αIIbβ3 integrin, thus promoting blood coagulation. In addition to their primary function in blood clotting, fibrinogen and fibrin also play a role in various physiological reactions including fibrinolysis, cellular and matrix interactions, wound healing and neoplasia

Fibrinogen γ′ in ischemic stroke: A case-control study

BACKGROUND AND PURPOSE - To determine the contribution of fibrinogen γ′ levels and FGG haplotypes to ischemic stroke. METHODS - Associations between fibrinogen γ′ levels, fibrinogen γ′/total fibrinogen ratio, and FGG haplotypes with the risk of ischemic stroke were determined in 124 cases and 125 controls. RESULTS - Fibrinogen γ′/total fibrinogen ratio was higher in patients than in controls during the acute phase of the stroke and lower in the convalescent phase 3 months after the stroke. FGG haplotype 3 (H3) was associated with a reduced risk of ischemic stroke (odds ratio 0.60; 95% CI, 0.38 to 0.94), but not with the fibrinogen γ′/total fibrinogen ratio. In contrast, FGG-H2 was associated with a decreased fibrinogen γ′/total fibrinogen ratio, but not with risk of stroke. CONCLUSIONS - Fibrinogen γ′/total fibrinogen ratio is associated with ischemic stroke, especially in the acute phase of the disease. In addition, FGG-H3 haplotype appears to be protective against ischemic stroke

γ/total fibrinogen ratio is associated with short-term outcome in ischaemic stroke

Fibrinogen γ' (γ') is a natural isoform of fibrinogen, and alters the rate of formation and the properties of clots. It could therefore affect outcome after ischaemic stroke. The prognostic significance of γ' fibrinogen levels is, however, still unclear. It was the objective of this study to assess levels of γ' in ischaemic stroke, and its association with short-term outcome. We included 200 ischaemic stroke patients and 156 control persons. Total fibrinogen and γ' levels were measured; outcome at discharge was assessed by means of the modified Rankin Scale score (defined as unfavourable when >2). We compared levels between patients and controls using multiple linear regression analysis, and logistic regression analysis was used to assess the relationship between levels and outcome. All analyses were adjusted for age and sex. Mean γ' levels were significantly higher in patients with ischaemic stroke than in controls (0.37 vs. 0.32 g/l, p<0.001), and patients also had a higher γ'/total fibrinogen ratio (0.102 vs. 0.096, p=0.19). The γ'/total fibrinogen ratio is associated with unfavourable outcome in patients with ischaemic stroke (odds ratio per unit increase of γ'/total fibrinogen ratio 1.27, 95% confidence interval 1.09-1.47). Our study shows that patients with ischaemic stroke have increased levels of fibrinogen γ' and suggests a trend towards an increased γ'/total fibrinogen ratio in ischaemic stroke. Increased fibrinogen γ' relative to total fibrinogen levels are associated with unfavourable outcome in the early phase after stroke