Zöller B, Dahlbäck B
University of Lund, Malmö General Hospital, Sweden.
Curr Opin Hematol. 1995 Sep;2(5):358-64. doi: 10.1097/00062752-199502050-00006.
Each year, approximately one in 1000 individuals suffers from venous thromboembolism. The pathogenesis of the disease is multifactorial and a thrombotic event is the result of a combination of genetic and circumstantial risk factors. Until recently, genetic defects could only be identified in a minority of thrombosis patients. The discovery of inherited resistance to activated protein C as a risk factor for thrombosis changed the situation for the better. In Western countries, activated protein C resistance is found in 20% to 60% of patients with thrombosis. Activated protein C resistance is caused by a single point mutation in the Factor V gene, leading to replacement of Arg(R)506 in the activated protein C cleavage site of Factor V with a Gln(Q). As a result, the activated protein C-mediated cleavage and inhibition of mutated Factor V (FV:Q506) is impaired, which leads to increased thrombin generation, a hypercoagulable state, and a life-long increased risk of thrombosis.
每年，每1000人中约有1人患有静脉血栓栓塞症。该疾病的发病机制是多因素的，血栓形成事件是遗传和环境风险因素共同作用的结果。直到最近，只有少数血栓形成患者能够被鉴定出基因缺陷。遗传性活化蛋白C抵抗作为血栓形成的一个风险因素的发现使情况得到了改善。在西方国家，20%至60%的血栓形成患者存在活化蛋白C抵抗。活化蛋白C抵抗是由凝血因子V基因中的一个单点突变引起的，导致凝血因子V活化蛋白C裂解位点的精氨酸（R）506被谷氨酰胺（Q）取代。结果，活化蛋白C介导的突变凝血因子V（FV:Q506）的裂解和抑制受到损害，这导致凝血酶生成增加、高凝状态以及终身血栓形成风险增加。
