Factor I (Fibrinogen) Deficiency
Factor I deficiency is a collective term for three rare inherited fibrinogen deficiencies. It was first described in 1920 by two German physicians. Fibrinogen helps platelets stick together to form the initial “plug” after an injury. Fibrinogen deficiencies can be quantitative or qualitative, depending on whether the fibrinogen is deficient or defective. The quantitative disorders are afibrinogenemia, when fibrinogen is absent, and hypofibrinogenemia, when some protein with normal structure is present but below levels needed for normal clotting. Dysfibrinogenemia is a qualitative disorder in which normal amounts of fibrinogen are manufactured by the liver, but they don’t clot properly.
Factor I deficiency is inherited in an autosomal recessive fashion, which means that both parents must carry the gene to pass it on to their children; it affects men and women equally. Afibrinogenemia is very rare, occurring in 1-2 people per million.. Dysfibrinogenemia is inherited in an autosomal dominant manner, which means that only one parent must carry the gene to pass it on to a child. Hypofibrinogenemia can be inherited in either manner.
Afibrinogenemia and hypofibrinogenemia are usually diagnosed in newborns who exhibit excessive bleeding from the umbilical cord and after circumcision. Easy bruising, nose and mouth bleeds, and soft tissue bleeds are common. Joint and muscle bleeds can also occur. Women with afibrinogenemia typically have menorrhagia (long, heavy periods) and difficulties carrying a baby to term because fibrinogen plays a role in embryo implantation. People with dysfibrinogenemia experience prolonged wound healing and are at increased risk of blood clots in the veins.
Tests to diagnose factor I deficiency measure the amount of fibrinogen in the blood and the time it takes for the blood to clot during the prothrombin time (PT) test, activated partial thromboplastin time (aPTT) test and thrombin clotting time (TCT) test.
In 2009, the FDA approved RiaSTAP™, the first factor concentrate, to treat afibrinogenemia and hypofibrinogenemia in patients with <50 mg/dL of fibrinogen. RiaSTAP cannot be used in patients with dysfibrinogenemia because of the risk of blood clots. For them, fresh frozen plasma or cryoprecipitate is recommended.
In 2017, the FDA approved Fibryga®, a human plasma-derived fribrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and adolescents with afibrinogenemia and hypofibrinogenemia. It is administered via intravenous infusion. Fibryga is not indicated for dysfibrinogenemia.