title: Ocular vascular thrombotic events: a diagnostic window to familial thrombophilia (compound factor V Leiden and prothrombin gene heterozygosity) and thrombosis.
abstract: In a 12-member, 3-generation kindred with conjoint inheritance of G1691A factor V Leiden (FVL) and G20210A prothrombin gene (PTG) mutations, identified through a proband with amaurosis fugax and his father with nonarteritic ischemic optic neuropathy (NAION), the authors' hypothesis was that ocular thrombosis was a diagnostic window to familial thrombophilia-thrombosis. The authors used polymerase chain reaction (PCR) measures for thrombophilia (FVL, PTG, C677T-A1298C methylenetetrahydrofolate reductase [MTHFR], platelet glycoprotein PLA1A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). The 39-year-old white male proband, with amaurosis fugax and transient ischemic attacks (TIA), was found to be a compound heterozygote for FVL and PTG mutations. His symptoms resolved only after coumadin. His 44-year-old brother (deep venous thrombosis [DVT]) and 46-year-old sister (DVT, pulmonary embolus [PE]) were compound FVL-PTG gene heterozygotes. Of 4 asymptomatic children born to these 3 siblings, 2 were FVL heterozygotes and 2 PTG heterozygotes. The proband's 69-year-old father, with NAION and ischemic stroke, had PTG heterozygosity, familial high factor VIII, and compound MTHFR C677T-A1298C mutation with homocysteinemia. The proband's 61-year-old aunt had PTG heterozygosity, recurrent DVT, and mesenteric artery thrombosis. The proband's 67-year-old mother, free of thrombotic events, was a FVL heterozygote, had high factor VIII, and PAI-1 4G4G homozygosity. In this extended kindred, ocular thrombotic events (amaurosis fugax, NAION) were associated with variegated thrombotic events, including TIA, ischemic stroke, DVT, PE, and mesenteric artery thrombosis, and opened a diagnostic window to family screening and treatment for complex thrombophilias, which had previously been undiagnosed.
authors.affiliation: Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA. glueckch@healthall.com
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D020757:Amaurosis Fugax / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D006801:Humans; D008297:Male; D018917:Optic Neuropathy, Ischemic / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics*; D011655:Pulmonary Embolism / Q000235:genetics; D019851:Thrombophilia / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin