FAMILIAL PROTEIN S DEFICIENCY IS ASSOCIATED WITH RECURRENT THROMBOSIS
FAMILIAL PROTEIN S DEFICIENCY IS ASSOCIATED WITH RECURRENT THROMBOSIS
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DOI：
10.1172/jci111632
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
ESMON, CT
中科院分区：
文献类型：
--
作者：
COMP, PC;NIXON, RR;ESMON, CT
最近的研究表明，蛋白C缺乏与复发性家族性血栓形成有关。在血浆中，活化蛋白C起着抗凝血剂的作用。这种抗凝反应需要依赖维生素k的血浆蛋白辅助因子，即蛋白S。由于活化蛋白C的抗凝活性依赖于蛋白S，因此假设缺乏功能性蛋白S的患者可能患有相关的血栓性疾病。本报告描述了两例其他凝血试验正常的相关个体，其血浆不能有效地用活化蛋白C抗凝。将纯化的人蛋白S添加到他们的血浆中，恢复了对活化蛋白c的正常抗凝反应。一种快速的1阶段蛋白S凝血试验被开发出来，用于定量血浆中蛋白S的水平。用固定的抗S蛋白抗体免疫吸附法去除血浆中的S蛋白。所得血浆对活化蛋白C反应较差，但在添加纯化蛋白S或少量血浆后，以剂量依赖的方式有效抗凝。受影响个体的蛋白S活性< 5%。使用劳雷尔火箭，在血浆中检测到蛋白S抗原，但在2个人中降低了13%和18%的水平。当患者血浆Ba洗脱液在季氨基乙基Sephadex上进行色谱分析时，在色谱早期检测到缺乏蛋白S抗凝辅因子活性的蛋白S抗原单峰。正常供体Ba洗脱液出现2个峰，1个峰出现较早且无抗凝辅助因子，2个峰出现较晚，具有抗凝活性。蛋白S抗原的第一个峰，来自正常供体和患者，在补体组分c4结合蛋白-蛋白S复合物区域层析。蛋白S缺乏可导致复发性血栓性疾病。
Recent studies have demonstrated that protein C deficiency is associated with recurrent familial thrombosis. In plasma, activated protein C functions as an anticoagulant. This anticoagulant response requires a vitamin K-dependent plasma protein cofactor, referred to as protein S. Since the anticoagulant activity of activated protein C is dependent on protein S, it was hypothesized that patients lacking functional protein S might have associated thrombotic disease. Two related individuals with otherwise normal coagulation tests whose plasma was not effectively anticoagulated with activated protein C were described. Addition of purified human protein S to their plasma restored a normal anticoagulant response to activated protein C. A rapid 1-stage clotting assay for protein S was developed to quantitate the level of protein S in plasma. Plasma was depleted of protein S by immunoadsorption with immobilized antiprotein S antibodies. The resultant plasma responded poorly to activated protein C, but was effectively anticoagulated in a dose-dependent fashion upon addition of purified protein S or small quantities of plasma. The affected individuals possess < 5% protein S activity. Using Laurell rockets, protein S antigen was detected in the plasma but was at reduced levels of 13 and 18% in the 2 individuals. When the Ba eluate of the patient plasma was chromatographed on quaternary aminoethyl Sephadex, a single peak of protein S antigen devoid of protein S anticoagulant cofactor activity was detected early in the chromatogram. In contrast, the Ba eluate from normal donors separated into 2 peaks, 1 emerging early and also devoid of anticoagulant cofactor and the 2nd peak with anticoagulant activity emerging later. The 1st peak of protein S antigen, from both the normal donor and the patient, chromatographed in the region of the complement component C4-binding protein-protein S complex. Protein S deficiency may result in recurrent thrombotic disease.