Congenital Afibrinogenemia, Hypofibrinogenemia, Dysfibrinogenemia

Afibrinogenemia is a rare genetic disorder of hemostasis occurring with an estimated prevalence of approximately 1 in 1,000,000. This is an autosomal recessive disorder mostly seen in communities where consanguinity is prevalent (India, Pakistan, and the Middle East). Afibrinogenemia results in altered hemostasis, poor inflammatory response (fibrinogen is an acute-phase reactant), and delayed wound healing because of a distorted cellular and matrix interaction. Dysfibrinogenemia is an autosomal-dominant disorder causing bleeding and thrombosis. Thrombosis occurs among about 20% of patients with dysfibrinogenemia. There appears to be no direct correlation between functional fibrinogen and clinical features in dysfibrinogenemia. Until recently, fresh frozen plasma and cryoprecipitate were the mainstays of treatment, but the newer fibrinogen concentrates are favored because of the infective/allergic complications of the blood products. However, the fibrinogen concentrates (4 FDA-approved agents) are still not advised for dysfibrinogenemia with thrombotic symptoms. Furthermore, acquired causes of hypo-/dysfibrinogenemia are by far more common, and these should be excluded from evaluating patients with defective fibrinogen synthesis.