Abstract

Afibrinogenemia is a rare blood clotting disorder with an estimated prevalence of 1: 1,000,000. It is an autosomal recessive disease caused by mutations in one of the three genes encoding the three polypeptide chains of fibrinogen located on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor trauma, and excessive bleeding during interventional procedures are the main symptoms. Replacement therapy is the mainstay of management of bleeding episodes in these patients, with plasma-derived fibrinogen concentrate being the drug of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments that should only be used when fibrinogen concentrate is not available. Secondary preventive treatment can be considered after life-threatening bleeding, but primary preventive treatment is currently not recommended. We also discuss alternative treatment options and management of surgery, pregnancy, and thrombosis in these patients. New tests to identify at-risk patients and the development of safer replacement therapies will improve the treatment of afibrinogenemia in the future.