Zöller B, Hillarp A, Berntorp E, Dahlbäck B
Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden.
Annu Rev Med. 1997;48:45-58. doi: 10.1146/annurev.med.48.1.45.
Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution or arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found fewer than 10-15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20-60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1-15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.
遗传性活化蛋白C（APC）抵抗最近被发现是家族性血栓形成倾向的一个原因，现在已知它是静脉血栓形成最常见的遗传风险因素。它由因子V基因中的一个单点突变引起，该突变预测第506位的精氨酸（R）被谷氨酰胺（Q）取代。因此，与正常的活化因子V（FVa:R506）相比，突变的活化因子V（FVa:Q506）被活化蛋白C降解得更慢，导致血液高凝状态以及静脉血栓形成的终生风险增加5至10倍。先前已知的遗传性血液高凝状态，即抗凝血蛋白抗凝血酶III、蛋白S和蛋白C的缺乏，在西方国家血栓形成患者中发现的比例不到10%至15%，而遗传性APC抵抗在这类患者中的比例为20%至60%。FV突变在白种人起源的人群中很常见，患病率在1%至15%之间，而在某些其他种族群体如日本人和中国人中未发现。APC抵抗的高患病率，加上简单实验室检测方法的可用性，将对血栓形成的治疗和预防方案的发展产生深远影响，并有望降低血栓栓塞事件的发生率。
