Glueck C J, Goldenberg Naila, Bell Howard, Golnik Karl, Wang Ping
Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA.
Clin Appl Thromb Hemost. 2005 Jul;11(3):235-41. doi: 10.1177/107602960501100301.
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.
本研究的目的是前瞻性评估一过性黑矇、遗传性易栓症和获得性易栓症之间的关联。对11例（8名女性，3名男性；均为白人）一过性黑矇患者进行了易栓症和纤溶功能减退研究，这些患者年龄为57±17岁，入选标准为无脑磁共振成像（MRI）、磁共振血管造影（MRA）、磁共振静脉造影（MRV）异常，同侧颈内动脉斑块、房颤或心脏血栓。将这些病例与78名健康成年白人对照（53±18岁）进行血清学指标比较，并通过聚合酶链反应与248名健康白人对照（78名成年人，170名儿童）进行基因突变比较。所有11例患者均有一种或多种家族性易栓性凝血障碍，包括1例G1691A因子V Leiden突变杂合子、2例游离蛋白S水平低、4例因子VIII水平高、3例对活化蛋白C抵抗、3例C677T亚甲基四氢叶酸还原酶（MTHFR）突变纯合子、2例C677T - A1298C MTHFR复合杂合子以及3例PAI - 1基因4G4G纯合子导致的纤溶功能减退。因子VIII为160%的病例还存在另外两种易栓症（复合MTHFR C677T - A1298C杂合子、对活化蛋白C抵抗）以及纤溶功能减退性高Lp(a)。10例病例中有5例（50%）存在血栓ophilic C677T MTHFR纯合子或复合C677T - A1298C杂合子，而248名对照中有30例（12%）存在，Fisher's p（p(f)）=0.005。10例病例中有4例（40%）因子VIII水平高，而38名对照中无1例，p(f)=0.001。8名女性中有5例（4例使用外源性雌激素，1例怀孕）存在血栓ophilic高雌激素血症，可能与遗传性易栓症 - 纤溶功能减退相互作用，促进血栓形成。在入选标准为无脑磁共振成像异常、同侧颈内动脉明显斑块、房颤或心脏血栓的病例中，我们推测一过性黑矇可能由与遗传性易栓症和/或纤溶功能减退相关的可逆性（通过抗凝）视网膜动脉血栓引起，雌激素驱动的获得性易栓症常使其加重。
