Thrombophilia Due To Thrombin Defect; Thph1

Description

Thrombophilia is a multifactorial disorder of inappropriate clot formation resulting from an interaction of genetic, acquired, and circumstantial predisposing factors. Venous thromboembolism most commonly manifests as deep vein thrombosis, which may progress to pulmonary embolism if the clot dislodges and travels to the lung. Other manifestations include thromboses of the cerebral or visceral veins and recurrent pregnancy loss (summary by Seligsohn and Lubetsky, 2001 and Varga and Kujovich, 2012). Genetic Heterogeneity of ThrombophiliaTHPH2 (OMIM ) is caused by mutation in the F5 gene (OMIM ) on chromosome 1q23; THPH3 (OMIM ) and THPH4 (OMIM ) are both caused by mutation in the PROC gene (OMIM ) on 2q; THPH5 (OMIM ) and THPH6 (OMIM ) are caused by mutation in the PROS1 gene (OMIM ) on 3q11; THPH7 (OMIM ) is caused by mutation in the AT3 gene (OMIM ) on 1q25; THPH8 (OMIM ) is caused by mutation in the F9 gene (OMIM ) on Xq27; THPH9 (OMIM ) is associated with decreased release of tissue plasminogen activator (PLAT ); THPH10 (OMIM ) is caused by mutation in the HCF2 gene (OMIM ) on 22q11; THPH11 (OMIM ) is caused by mutation in the HRG gene (OMIM ) on 3q27; and THPH12 (OMIM ) is associated with variation in the THBD gene (OMIM ) on 20p11.Susceptibility to thrombosis has also been associated with variation in additional genes, including MTHFR ({607093.0003}); F13B ({134580.0003}); plasminogen activator inhibitor (SERPINE1 ); and several genes encoding fibrinogen (FGA, {134820}; FGB, {134830}; FGG, {134850}). Variation in the SERPINA10 (see {605271.0001}), KNG1 (OMIM ) and HABP2 (OMIM ) genes has also been reported.Protection against venous thrombosis is associated with variation in the F13A1 gene (OMIM ) on 6p25.

Clinical Features

• Neoplasm
• Gastrointestinal hemorrhage
• Venous thrombosis
• Thromboembolism
• Pulmonary embolism
• Deep venous thrombosis
• Hypercoagulability
• Cerebral venous thrombosis
• Recurrent deep vein thrombosis
• Recurrent thrombophlebitis