Discordant fibrin formation in hemophilia.

Background: The conversion of fibrinogen to fibrin and its crosslinking to form a stable clot are key events in providing effective hemostasis.

Objectives: To evaluate the relationship of fibrinopeptide (FP) release and factor (F) XIII activation in whole blood from hemophiliacs.

Patients/methods: We investigated FPA and FPB release, FXIII activation and fibrin mass in tissue factor-initiated coagulation in whole blood from individuals with hemophilia and healthy subjects.

Results: In hemophiliacs, the rates of fibrin formation were delayed as compared to healthy individuals. FPA/FPB release and FXIII activation were decreased in hemophiliacs vs. healthy individuals: 5.4 +/- 0.7 microM min(-1) to 1.7 +/- 0.4 microM min(-1) (P = 0.003), 2.3 +/- 0.6 microM min(-1) to 0.5 +/- 0.1 microM min(-1) (P = 0.025), and 12.1 +/- 0.7 nM min(-1) to 3.1 +/- 0.7 nM min(-1) (P < 0.0005), respectively. More FPA was released in hemophiliacs (6.6 +/- 1.2 microM) prior to clot time (CT) than in healthy individuals (2.6 +/- 0.4 microM, P = 0.013), whereas FPB and activated FXIII levels remained comparable. FXIII activation, which normally coincides with FPA release, was delayed in hemophiliacs. At CT in normal blood, the FPA concentration was 2.6-fold higher than that of FPB (P = 0.003), whereas in hemophiliacs this ratio was increased to 6.6-fold (P = 0.001).

Conclusions: These data suggest that essential dynamic correlations exist between the presentations of fibrin I, fibrin II, and FXIIIa. The 'discordance' of fibrin formation in hemophiliacs results in clots that are more soluble than normal (43% lower mass; P = 0.02). The resulting poor physical clot strength probably plays a crucial role in the pathology of hemophilia.