Sun X, Evatt B, Griffin J H
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.
Blood. 1994 Jun 1;83(11):3120-5.
A coagulation test abnormality, termed activated protein C (APC) resistance, involving poor anticoagulant response to APC is currently the most common laboratory finding among venous thrombophilic patients. Because the anticoagulant activity of APC involves inactivation of factors Va and VIIIa, studies were made to assess the presence of abnormal factors V or VIII. Diluted aliquots of plasma from two unrelated patients with APC resistance and thrombosis were added to either factor VIII-deficient or factor V-deficient plasma and APC resistance assays were performed. The results suggested that patients' factor V but not factor VIII rendered the substrate plasma APC resistant. When factor V that had been partially purified from normal or APC resistant patients' plasmas using immunoaffinity chromatography was added to factor V-deficient plasma, APC resistance assays showed that patients' factor V or factor Va, but not normal factor V, rendered the substrate plasma resistant to APC. Studies of the inactivation of each partially purified thrombin-activated factor Va by APC suggested that half of the patients' factor Va was resistant to APC. These results support the hypothesis that the APC resistance of some venous thrombophilic plasmas is caused by abnormal factor Va.
一种凝血试验异常，称为活化蛋白C（APC）抵抗，即对APC的抗凝反应不佳，是目前静脉血栓形成倾向患者中最常见的实验室检查结果。由于APC的抗凝活性涉及因子Va和VIIIa的失活，因此开展了研究以评估异常的因子V或VIII的存在情况。将两名无亲缘关系的患有APC抵抗和血栓形成的患者的血浆稀释等分试样添加到因子VIII缺乏或因子V缺乏的血浆中，并进行APC抵抗测定。结果表明，患者的因子V而非因子VIII使底物血浆对APC产生抵抗。当使用免疫亲和色谱法从正常或APC抵抗患者的血浆中部分纯化的因子V添加到因子V缺乏的血浆中时，APC抵抗测定表明，患者的因子V或因子Va而非正常因子V使底物血浆对APC产生抵抗。对APC使每种部分纯化的凝血酶激活的因子Va失活的研究表明，一半患者的因子Va对APC具有抗性。这些结果支持以下假说：某些静脉血栓形成倾向血浆的APC抵抗是由异常的因子Va引起的。
