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Impact of fibrinogen infusion on thrombin generation and fibrin clot structure in patients with inherited afibrinogenemia.

INTRODUCTION: Inherited afibrinogenemia is a very rare disease characterized by complete absence of fibrinogen in the circulation and an increased risk in both thrombosis and bleeding. Infusion of fibrinogen concentrate (FC) is the main approach for prevention and management of bleeding; however, it has been reported to carry a thrombotic risk.

METHODS: We investigated the impact of a standard dose (40-100 mg/kg) of FC infusion on the thrombin generation (TG) parameters and the fibrin clot structure formed in plasma samples of patients with afibrinogenemia. Blood samples were collected from 20 patients before (T0) and 1 hour after infusion of FC (T1). TG was studied with Calibrated Automated Thrombography. Fibrin clot structure was assessed with turbidimetry and scanning electron microscopy (SEM).

RESULTS: FC infusions (mean Clauss fibrinogen plasma level 1.21 g/L at T1) led to a statistically significant increase in endogenous thrombin potentials (ETP) (p<0.0001) and thrombin peaks (p=0.02). Nevertheless, when compared to healthy controls, patients' T1 lag times were longer (p=0.002), ETP values were lower (p=0.0003), and thrombin peaks were lower (p<00001). All fibrin polymerization parameters (turbidimetry) obtained at T1 were comparable to those of patients with inherited hypofibrinogenemia matched for fibrinogen plasma levels.

CONCLUSIONS: In summary, fibrinogen infusion with a standard dose of FC increased but did not correct TG and led to formation of fibrin clots similar to those of patients with hypofibrinogenemia. All in all, our results do not support to biological evidence of hypercoagulability induced by FC in patients with afibrinogenemia.

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