Severe hemophilia and physiologic inhibitors of coagulation

Patients with hemophilia demonstrate quite variable clinical phenotype even in cases with the same level of deficient factor or the same molecular abnormality. Different interacting factors including congenital and acquired alterations of coagulation inhibitors can modulate both clinical expression and severity of hemophilia. In this study, plasma levels of factor VIII (FVIII), factor IX (FIX) as well as protein C (PC), protein S (PS), and antithrombin (AT) plasma levels were measured in 80 patients with severe hemophilia A and B. Patients were divided into two groups according to the risk of bleeding: the first group (n = 32) with mild bleeding (< 2 bleeds/year), and the second group (n = 48) with severe bleeding (> or = 2 bleeds/year). Both hemophilia groups showed significantly decreased PC plasma levels compared to levels in healthy control subjects (the first group: p < 0.0001 and second group: p < 0.01). The difference in PC plasma levels between the first and second hemophilia group was significant (p < 0.05). Moreover, there was positive correlation between age and the functional PC in both hemophilia groups. Our results suggest that decreased PC plasma levels can testify to a slightly protective effect of the PC pathway on the severity and frequency of bleeding in patients with severe hemophilia A and B.