Fibrinogen replacement therapy for congenital fibrinogen deficiency

Abstract

Summary. This review of published studies was conducted to derive data on patients with congenital fibrinogen deficiency (CFD), including dosing of fibrinogen replacement therapy, outcome, and adverse events, either temporally related or distant to fibrinogen replacement, in order to assist clinicians in developing treatment plans for patients with CFD. A systematic review was performed of case reports identified by a MEDLINE search between 1961 and 2010. Eligible studies included subjects with a diagnosis of CFD who received fibrinogen replacement. An attempt was made to extract dose, frequency, duration, hemostatic efficacy and adverse events such as thrombosis or allergic reactions. Reported thrombotic events distant from fibrinogen replacement were also recorded. From 104 papers reviewed, a total of 50 cases were identified: afibrinogenemia (35), hypofibrinogenemia (6), and dysfibrinogenemia (9). Fibrinogen replacement therapy was generally effective in preventing or treating bleeding in doses adequate to achieve and maintain fibrinogen activity above 50–100 mg dL−1 (non‐surgical and obstetric use) or 100–200 mg dL−1 (surgical prophylaxis). Increased fibrinogen clearance was observed with massive hemorrhage, major surgery, and advanced pregnancy. Obstetric outcomes were optimized when fibrinogen replacement was initiated prior to conception. Uncontrolled hemorrhage, allergic reactions and antibody formation were rare events. However, thromboses, both related and unrelated to fibrinogen replacement, occurred in 15 of 50 (30%) patients overall, and in eight of 12 (67%) adult non‐obstetric patients with afibrinogenemia. Published fibrinogen replacement regimens are presented for 50 CFD patients. Fibrinogen replacement therapy requires careful monitoring of fibrinogen levels. Afibrinogenemia is associated with thromboembolic complications with or without treatment.

Management of Congenital Afibrinogenemia: Report of Two Cases

“…In March 2006, she first presented with fever and right leg swelling for 2 days at the age of 4 years. Her examination revealed normal findings with no obvious pallor or bleed except for of fibrinogen, but methylene blue/visible light treatment of cryoprecipitate may reduce the fibrinogen level by 40% [9]. Each unit of cryoprecipitate contains 140 mg of Fibrinogen.…”

“…Each unit of cryoprecipitate contains 140 mg of Fibrinogen. Classically, virally-inactivated FFP is preferred over non-virally inactivated cryoprecipitate [9,10]. Compared to cryoprecipitate, HFC offers more benefits in terms of purity, accuracy of dosing, feasibility of administration, and improved safety [9].…”

Management of Inherited Bleeding Disorders in Pregnancy

“…175,[195][196][197] In the neonate, afibrinogenaemia has been associated with ICH and umbilical bleeding. 189,198 Although fibrinogen levels increase during pregnancy, 87 this does not necessarily protect against complications.…”

“…191,192,194 Thrombotic complications are very common in patients with congenital fibrinogen deficiency, with or without fibrinogen replacement therapy. 198 LMWH prophylaxis has been used both antenatally and postpartum. 200,201 Fibrinogen replacement therapy does not necessarily prevent all pregnancy complications, 198 possibly due to difficulty maintaining adequate trough levels.…”

“…198 LMWH prophylaxis has been used both antenatally and postpartum. 200,201 Fibrinogen replacement therapy does not necessarily prevent all pregnancy complications, 198 possibly due to difficulty maintaining adequate trough levels.…”