Results of an international, multicentre pharmacokinetic trial in congenital fibrinogen deficiency.
Results of an international, multicentre pharmacokinetic trial in congenital fibrinogen deficiency
Rare bleeding disorders represent 3–5% of all inherited coagulation factor disorders. Inherited afibrinogenemia, which is caused by a deficiency in plasma fibrinogen (coagulation factor I), accounts for only a small portion of all the rare bleeding disorders. Patients with afibrinogenemia have a variable bleeding pattern that may include potentially serious or life-threatening haemorrhages. Treatment of afibrinogenemia is aimed at replacing the missing fibrinogen to restore efficient haemostasis and to stop bleeding. Three sources of fibrinogen are currently available: fresh frozen plasma, cryoprecipitate, and lyophilized fibrinogen concentrate. Owing to its rarity, little is known about the optimal treatment of patients with afibrinogenemia, including the pharmacokinetics of fibrinogen concentrate. To explore this further, we conducted a prospective, open-label, uncontrolled, multinational pharmacokinetic trial of pasteurized human fibrinogen concentrate in 15 patients with afibrinogenemia. Infusion of a single dose of fibrinogen concentrate (70 mg/kg body weight) resulted in similar fibrinogen antigen and activity levels, which were highly correlated. Fibrinogen levels rose rapidly following infusion to reach a maximum of approximately 1.3 g/L at 1 hour. Fibrinogen concentrate effectively restored clot formation, based on the surrogate thromboelastographic end-point of maximum clot firmness. The concentrate was well tolerated and there were no treatment-related adverse events or evidence of viral transmission during the study.