The aim of this study was to prospectively assess associations between
amaurosis fugax, inherited
thrombophilia, and acquired
thrombophilia.
Thrombophilia and hypofibrinolysis were studied in 11 cases (eight women, three men; all white) with
amaurosis fugax, 57 +/- 17 years old, selected by the absence of abnormal brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), magnetic resonance venography (MRV), ipsilateral internal carotid artery plaque,
atrial fibrillation, or cardiac
thrombus. Cases were compared to 78 healthy adult white controls (53 +/- 18 years old) for serologic measures, and by polymerase chain reaction to 248 healthy white controls (78 adults, 170 children) for gene mutations. All 11 cases had one or more familial thrombophilic coagulation disorder including one heterozygous for the G1691A
factor V Leiden mutation, two with low free
protein S, four with high
factor VIII, three with resistance to activated
protein C, three homozygous for the C677T
methylenetetrahydrofolate reductase (MTHFR) mutation, two compound C677T-A1298C MTHFR heterozygotes, and three with hypofibrinolytic 4G4G homozygosity for the
PAI-1 gene. The case with
factor VIII of 160% had two other
thrombophilias (compound MTHFR C677T-A1298C heterozygosity, resistance to activated
protein C), and hypofibrinolytic high Lp(a). Thrombophilic C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in five of 10 (50%) cases vs. 30 of 248 (12%) controls, Fisher's p (p(f)) = .005. Thrombophilic
factor VIII was high in four of 10 (40%) cases vs. 0 of 38 controls, p(f) = .001. Thrombophilic hyperestrogenemia in five of the eight women (four exogenous
estrogen, one pregnant) may have interacted with inherited
thrombophilia-hypofibrinolysis, promoting
thrombus formation. In cases selected by the absence of abnormal brain magnetic resonance imaging, significant ipsilateral internal carotid artery plaque,
atrial fibrillation, or cardiac
thrombus, we speculate that
amaurosis fugax can be caused by reversible (by anticoagulation) retinal artery thrombi associated with heritable
thrombophilia and/or hypofibrinolysis, often augmented by
estrogen-driven acquired
thrombophilia.