Treatment of congenital fibrinogen deficiency: overview and recent findings

Abstract

Afibrinogenemia is a rare bleeding disorder with an estimated prevalence of 1:1,000,000. It is an autosomal recessive disease resulting from mutations in any of the 3 genes that encode the 3 polypeptide chains of fibrinogen and are located on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor trauma and excessive bleeding during interventional procedures are the principal manifestations. We review the management of afibrinogenemia. Replacement therapy is the mainstay of treatment of bleeding episodes in these patients and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments that should be used only when fibrinogen concentrate is not available. Secondary prophylactic treatment may be considered after life-threatening bleeding whereas primary prophylactic treatment is not currently recommended. We also discuss alternative treatment options and the management of surgery, pregnancy and thrombosis in these patients. The development of new tests to identify higher risk patients and of safer replacement therapy will improve the management of afibrinogenemia in the future.

Chronic Subdural Hematoma in a Patient With Congenital Afibrinogenemia Successfully Treated With Fibrinogen Replacement -Case Report-

“…Fibrinogen is also important in primary hemostasis for normal platelet aggregation. 2,19) Afibrinogenemia refers to the total absence of fibrinogen and has an estimated prevalence 1:1000000. 15) The three separate genes encoding FGA, fibrinogen betachain, and fibrinogen gamma-chain are involved in causing afibrinogenemia.…”

“…13) The most common manifestations of afibrinogenemia are umbilical stump bleeding at birth and bleeding from the mucosal surface. 2,19) Although intracranial hemorrhage can present with rare coagulation disorder, lifethreatening intracranial hemorrhage is infrequent in adults, 14) with only 3 cases reported. 3,6,14) Two case reports 3,6) described spontaneous intracerebral hemorrhages which were treated conservatively with the administration of fibrinogen concentrates and the one case report 14) described acute epidural and subdural hematomas which were successfully evacuated via craniotomies using fibrinogen concentrate.…”

“…2,19) The fibrinogen level should be maintained above 1 g/l until hemostasis is secure and above 0.5 g/l until wound healing is complete. The suggested amount of fibrinogen is: dose (g) ＝ desired increment in g/l × plasma volume, where the plasma volume is 0.07 × (1 -hematocrit) × weight (kg).…”

“…Cryoprecipitate and FFP represent alternative replacement therapies and should be given only in emergencies when fibrinogen concentrate is not available. 19) Fibrin glue may be useful to treat superficial wounds. Tranexamic acid may be useful to prevent bleeding for surgical procedures, but should be used with caution in patients with a history of thrombosis because the risk of thrombosis may increase.…”

“…In later life, the disorder may be associated with bleeding from the mucosal surfaces, hemorrhage into the muscle and joints, spontaneous abortions, and spontaneous splenic rupture. 2,15,19) A small number of cases of spontaneous intracerebral bleeding in adults have been reported, 3,6,14) but none of chronic subdural hematoma (CSDH) with congenital afibrinogenemia. Here we report a case of CSDH in a 37-year-old woman that was successfully treated by burr-hole evacuation with administration of fibrinogen concentrate.…”