Schorer A E, Wickham N W, Watson K V
Department of Medicine, Minneapolis Veterans Administration Medical Center, MN 55417.
Br J Haematol. 1989 Mar;71(3):399-407. doi: 10.1111/j.1365-2141.1989.tb04298.x.
A patient with microvascular thrombosis and thrombocytopenia was found to have a high-titre lupus anticoagulant. The biological effects of the patient's lupus anticoagulant were studied using whole patient serum and plasma. Staph Protein A eluate, and affinity-purified lupus anticoagulant. The latter was isolated by immunoadsorption of serum onto cardiolipin/phosphatidylserine/cholesterol liposomes. Each source of lupus anticoagulant demonstrated 'anticoagulant' activity, defined as prolongation of a modified kaolin clotting time, and contained antibody which bound to endothelial monolayers. Each interfered with thrombin-mediated prostacyclin release from endothelial cells, but had no effect on arachidonate-induced prostacyclin release. In addition, the lupus anticoagulant selectively blocked platelet aggregation in response to thrombin, but not in response to arachidonate, ADP or epinephrine. Lupus anticoagulant also reduced thrombin-stimulated shifts in cytosolic calcium. Thrombin-mediated membrane inositol metabolism and total thrombin binding to endothelium were unaffected by lupus anticoagulant, and another endothelial anticoagulant function related thrombin binding. Protein C activation by thrombomodulin, was not altered. We conclude that the binding of lupus anticoagulant to endothelial cells and platelets does not prevent all thrombin signalling events, but does interrupt prostacyclin production.
一名患有微血管血栓形成和血小板减少症的患者被发现有高滴度狼疮抗凝物。使用患者全血清和血浆、葡萄球菌蛋白A洗脱液以及亲和纯化的狼疮抗凝物研究了该患者狼疮抗凝物的生物学效应。后者通过将血清免疫吸附到心磷脂/磷脂酰丝氨酸/胆固醇脂质体上分离得到。每种狼疮抗凝物来源均表现出“抗凝”活性，定义为改良高岭土凝血时间延长，且含有与内皮单层结合的抗体。每种都干扰凝血酶介导的内皮细胞前列环素释放，但对花生四烯酸诱导的前列环素释放无影响。此外，狼疮抗凝物选择性地阻断凝血酶诱导的血小板聚集，但不阻断花生四烯酸、二磷酸腺苷或肾上腺素诱导的血小板聚集。狼疮抗凝物还减少了凝血酶刺激的细胞内钙转移。凝血酶介导的膜肌醇代谢以及凝血酶与内皮的总结合不受狼疮抗凝物影响，且与另一种内皮抗凝功能相关的凝血酶结合也未改变。凝血酶调节蛋白对蛋白C的激活未发生改变。我们得出结论，狼疮抗凝物与内皮细胞和血小板的结合并不阻止所有凝血酶信号事件，但确实会中断前列环素的产生。
