Dahlbck B
Department of Clinical Chemistry, University of Lund, University Hospital, Malmö, Sweden.
J Intern Med Suppl. 1997;740:1-8.
The protein C system is an important natural anticoagulant pathway. Protein C is the key component of the system and it is activated by thrombin bound to thrombomodulin on the surface of endothelial cells. Activated protein C (APC) inhibits coagulation by cleaving and inactivating coagulation factors factor Va and factor VIIIa. Until recently, the major genetic causes of familial venous thrombophilia were inherited deficiencies of protein C, protein S or antithrombin, but together they were found in less than 5-10% of patients with thrombosis. In 1993, the situation changed drastically with the description of inherited APC-resistance as a novel risk factor for venous thrombosis. APC-resistance is characterized by a poor anticoagulant response to APC. Inherited APC-resistance is the most common genetic risk factor for this disease and it is found in 20-60% of patients. The condition is caused by a single point mutation in the gene for factor V which predicts substitution of arginine (R) at position 506 with a glutamine (Q). Mutated factor V (FVR506Q, FV:Q506 or FV Leiden) expresses normal procoagulant properties but is partially resistant to APC. The resulting hypercoagulable state confers a life long increased risk of venous but not arterial thrombosis. The FVR 506Q mutation is common in Caucasians with a prevalence of 1-15%, whereas it is not found in other human races. The FVR 506Q mutation may, due to its high prevalence, be an additional risk factor in individuals carrying other inherited defects such as deficiency of protein S, protein C or antithrombin. Such individuals have a high incidence of thrombosis and severe thrombophilia is a multigenetic disease. The high prevalence of inherited APC-resistance and the availability of easy functional and genetic tests will stimulate the development of prophylactic regimens and hopefully result in a decreased incidence of thrombosis.
蛋白C系统是一条重要的天然抗凝途径。蛋白C是该系统的关键成分，它在内皮细胞表面被结合于血栓调节蛋白的凝血酶激活。活化蛋白C（APC）通过裂解和灭活凝血因子Ⅴa和Ⅷa来抑制凝血。直到最近，家族性静脉血栓形成倾向的主要遗传病因是蛋白C、蛋白S或抗凝血酶的遗传性缺乏，但在血栓形成患者中，它们共同出现的比例不到5% - 10%。1993年，随着遗传性APC抵抗作为静脉血栓形成的一种新危险因素被描述，情况发生了巨大变化。APC抵抗的特征是对APC的抗凝反应不佳。遗传性APC抵抗是该病最常见的遗传危险因素，在20% - 60%的患者中存在。这种情况是由因子Ⅴ基因中的一个单点突变引起的，该突变预测第506位的精氨酸（R）被谷氨酰胺（Q）取代。突变的因子Ⅴ（FVR506Q、FV:Q506或FV莱顿）表现出正常的促凝血特性，但对APC有部分抗性。由此产生的高凝状态使静脉血栓形成的终生风险增加，但动脉血栓形成风险未增加。FVR 506Q突变在白种人中很常见，患病率为1% - 15%，而在其他种族中未发现。由于FVR 506Q突变患病率高，它可能是携带其他遗传性缺陷（如蛋白S、蛋白C或抗凝血酶缺乏）个体的额外危险因素。这类个体血栓形成发生率高，严重血栓形成倾向是一种多基因疾病。遗传性APC抵抗的高患病率以及简便的功能和基因检测方法的可用性将促进预防方案的发展，并有望降低血栓形成的发生率。
