Fibrinogen concentrate for bleeding in patients with congenital fibrinogen deficiency: Observational study of efficacy and safety for prophylaxis and treatment

Abstract

Background Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder characterized by reduced levels (afibrinogenemia, hypofibrinogenemia) or dysfunctional fibrinogen (dysfibrinogenemia), for which fibrinogen supplementation is the mainstay treatment. Objectives To assess the efficacy and safety of human fibrinogen concentrate (FCH) in patients with CFD. Methods This was a multicenter, noninterventional, retrospective cohort study with a 12‐month prospective follow‐up period in the United States and Canada. Individuals with CFD who received FCH for the treatment of bleeding, perioperative hemostasis, or prophylaxis were included. Data were collected retrospectively from medical records and every 3 months during the prospective period. Hemostatic efficacy was rated by the investigators as effective or ineffective using a 4‐point efficacy scale. Annualized bleeding rate (ABR) was summarized for patients who received FCH for routine prophylaxis. Results Twenty‐two patients were enrolled. FCH treatment was rated effective in treating ≥97.0% of bleeding events, in the retrospective and prospective periods. FCH was effective for perioperative hemostasis in ≥97.5% of minor and major surgeries across both periods. In patients treated with FCH for routine prophylaxis, the median ABRs for the retrospective and prospective period were 1.4 and 1.3, respectively. One adverse event (AE), thrombosis of the right cephalic vein, was reported as related to FCH treatment and resolved with a short course of anticoagulant. No serious AEs related to FCH or deaths were reported. Conclusions In patients with CFD, FCH is a well‐tolerated and effective treatment to achieve hemostasis during bleeding events and surgery and associated with infrequent bleeding events when used prophylactically.

Congenital Fibrinogen Deficiency in India and Role of Human Fibrinogen Concentrate

“…Lasky et al [52] reported the effectiveness of HFC with treating ≥97% of the bleeding events and perioperative hemostasis in ≥98.5% minor or major surgeries. The bleeding events in patients receiving HFC for routine prophylaxis were infrequent with median annualized bleeding rates of 1.4 and 1.3 for retrospective and prospective periods of the study, respectively.…”

“…In the FOR-MA-02 study, a single thrombotic event was reported in a patient, while allergic or hypersensitivity reactions were not observed [51]. Pallor, chills, cough, vomiting, headache, urticarial, erythematous rash [53], thrombosis [52], and anaphylactic reactions (hypotension, cyanosis, and abdominal and back pain) [53,56] have been reported.…”

Impact of Fibrinogen Infusion on Thrombin Generation and Fibrin Clot Structure in Patients with Inherited Afibrinogenemia

“…Plasma-derived fibrinogen concentrate (FC) is the optimal option as it generally considered safer and easier to handle compared to fresh frozen plasma and cryoprecipitate (4). Infusion of FC for treatment or prevention has been helpful in patients with afibrinogenemia (5). However, a potential link between FC and thromboembolism events have been reported (6), although causality is often not established, and pharmacovigilance data suggest that this risk, if any, is low (7,8).…”

“…4 Infusion of FC for treatment or prevention has been helpful in patients with afibrinogenemia. 5 However, a potential link between FC and thromboembolism events have been reported, 6 although causality is often not established, and pharmacovigilance data suggest that this risk, if any, is low. 7 8 To date pathogenesis of thrombosis in afibrinogenemia is only partially understood 9 and there are no reliable tools to identify which patients are at risk of thrombosis.…”

Cell Attachment Capacity and Compounds of Fibrin Membranes Isolated from Fresh Frozen Plasma and Cryoprecipitate

“…Cryoprecipitate was originally developed as a therapy for treating congenital factor VIII deficiency in the 1950s [ 7 ], but later it was also applied in the cases of von Willebrand disease, hypofibrinogenemia, or fibrinogen replacement therapy in fibrinogen deficiency [ 6 ]. However, in the case of fibrinogen deficiencies, cryoprecipitate has been largely replaced by human fibrinogen concentrates due to safety reasons [ 8 ].…”