In 8 men and 9 women (age 60 ± 14, all white) without ipsilateral atherosclerotic carotid plaque and with no other known causes of amaurosis fugax (AF), whose AF was associated with thrombophilia-hypofibrinolysis, we hypothesized that case-specific thromboprophylaxis (Coumadin-Lovenox, folic acid [5 mg]-B6 [100 mg]-B12 [2,000 μg], aspirin, cessation of exogenous estrogens, glucophage [2.5 g]) would prevent subsequent episodes of transient monocular partial or total blindness. All 17 cases had $ 1 thrombophilic-hypofibrinolytic disorder thought to be etiologic for AF. Seven cases had MTHFR C677T homozygosity or C677T-A1298C compound heterozygosity, 5 4G4G PAI-1 homozygosity, 4 high factor VIII, 4 lupus anticoagulant, 4 the platelet glycoprotein PL A1/A2 mutation, 2 low free protein S, 2 high plasminogen activator inhibitor activity (PAI-Fx), 1 V Leiden heterozygosity, 1 prothrombin gene (PTG) heterozygosity, and 1 protein C deficiency. In 4 cases on Coumadin for 16,16, 21, and 98 months (1 PTG heterozygote, 1 protein C deficient [41%], 1 free protein S deficient [53%] with high factor VIII [157%], and 1 with high factor VIII [207%]), AF resolved, usually within 1 month of starting Coumadin, and the patients remained asymptomatic provided that the INR remained 2.5 or higher. In 1 case with low free protein S (28%), treated for 8 months of pregnancy and 1 month postpartum on Lovenox 80 mg/day, AF disappeared within 1 week, and she remained asymptomatic. In 3 cases with MTHFR C677T homozygosity treated with folic acid-B6-B12 for 10, 15, and 29 months, AF resolved, usually within 1 month of starting therapy, and has not recurred. AF stopped within 1 month in 2 cases (1 high factor VIII 157%, 1 PAI-1 4G4G, PL A1/A2) when exogenous estrogens-SERMS were discontinued and has not recurred. The frequency of AF events was reduced in 2 cases on aspirin alone (1 PL A1/A2, I high VIII 157%) and AF events have remained less frequent over 5 and 11 months on aspirin. In 1 case with hypofibrinolysis (4G4G PAI-1 polymorphism, high PAI Fx, 31.7 IU/mL) treated with Glucophage (2.55 g/day), symptoms resolved within 1 month and have not recurred in 9 months on Glucophage. When AF occurs in the absence of carotid artery atherosclerosis or other known causes of AF, thrombophilia and/or hypofibrinolysis are nearly universal, reversible pathoetiologies.
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