ICD-11

Any disease caused by genetically inherited mutations leading to lack of coagulation factors in the blood not elsewhere classified. These diseases are characterised by increased haemorrhaging and bruising as the blood cannot clot properly to control bleeding. Confirmation is identification of mutations by genetic testing.

Congenital deficiencies of fibrinogen are coagulation disorders characterised by bleeding symptoms ranging from mild to severe resulting from reduced quantity and/or quality of circulating fibrinogen. Afibrinogenaemia (complete absence of fibrinogen) and hypofibrinogenaemia (reduced plasma fibrinogen concentration) correspond to quantitative anomalies of fibrinogen while dysfibrinogenaemia corresponds to a functional anomaly of fibrinogen. Hypo- and dysfibrinogenaemia may be frequently combined (hypodysfibrinogenaemia).

Congenital deficiencies of fibrinogen are coagulation disorders characterized by bleeding symptoms ranging from mild to severe resulting from reduced quantity and/or quality of circulating fibrinogen. Afibrinogenemia (complete absence of fibrinogen) and hypofibrinogenemia (reduced plasma fibrinogen concentration) correspond to quantitative anomalies of fibrinogen while dysfibrinogenemia corresponds to a functional anomaly of fibrinogen. Hypo- and dysfibrinogenemia may be frequently combined (hypodysfibrinogenemia) (see these terms). Prevalence of afibrinogenemia is estimated at 1/1,000,000. Hypo- and dysfibrinogenemia are more frequent. Men and women are equally affected. Fibrinogen deficiency can be discovered at any age but afibrinogenemia usually manifests early in childhood, often in the neonatal period. Common manifestations of afibrinogenemia include umbilical cord bleeding, epistaxis, hemarthrosis, gastrointestinal bleeding, menorrhagia, traumatic and surgical bleeding and, rarely, intracranial hemorrhage. Recurrent spontaneous abortions may occur in women affected with afibrinogenemia. Hypofibrinogenemia is characterized by fewer and milder bleeding episodes following trauma or surgery. Most of patients with dysfibrinogenemia are asymptomatic (60%). The others may have bleeding symptoms (28%) or even thrombosis (20%). Congenital deficiencies of fibrinogen are caused by mutations in the FGA, FGB, or FGG genes. Afibrinogenemia is autosomal recessive; hypofibrinogenemia and dysfibrinogenemia are mainly autosomal dominant. Diagnosis is based on prolonged activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin and reptilase times and on fibrinogen levels measured by functional (Clauss) and immunological assays. Differential diagnoses include the other congenital clotting factor deficiencies (see these terms) and acquired fibrinogen deficiency (consumptive coagulopathy, hepatic failure). In case of thrombosis, differential diagnosis also includes congenital or acquired thrombophilia (antithrombin deficiency, protein C or S deficiency, Factor V Leiden mutation, lupus anticoagulant (see these terms), FII Leiden mutation ...). Antenatal diagnosis of afibrinogenemia is possible if the causal mutations have already been identified in the family. Fibrinogen concentrates are usually used for the treatment of hemorrhages. Fresh frozen plasma is used when fibrinogen concentrates are not available. Recurrent spontaneous abortions can be prevented by routine prophylaxis based on administration of fibrinogen concentrates early in pregnancy. Although life-threatening intracranial hemorrhage may occur, prognosis of afibrinogenemia is good with early diagnosis and adequate treatment. Prognosis of hypo- or dysfibrinogenemia is usually good.