Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.
J Thromb Haemost. 2010 Mar;8(3):445-53. doi: 10.1111/j.1538-7836.2009.03711.x. Epub 2009 Nov 30.
Proteolytic inactivation of factors Va (FVa) and VIIIa (FVIIIa) by activated protein C (APC) and its cofactors protein S and factor V (FV) is a key process in the physiological down-regulation of blood coagulation. Functional abnormalities of this pathway, which manifest themselves in vitro as a poor anticoagulant response of plasma to added APC (APC resistance), are prevalent in the general population and are associated with an increased risk of venous thrombosis. APC resistance was originally discovered in thrombophilic families and later shown to be associated with the common FV Arg506Gln (FV(Leiden)) mutation, which abolishes one of the APC-cleavage sites in FV. Although FV(Leiden) is the major cause of hereditary APC resistance, it is becoming increasingly clear that several other genetic and acquired conditions contribute to APC resistance and thereby increase the risk of venous thrombosis. This paper reviews the multifactorial etiology of APC resistance and discusses its clinical implications.
蛋白 C（APC）及其辅助因子蛋白 S 和因子 V（FV）对因子 Va（FVa）和 VIIIa（FVIIIa）的蛋白水解失活是血液凝固的生理下调过程中的关键步骤。该途径的功能异常在体外表现为血浆对添加的 APC 的抗凝反应不良（APC 抵抗），在普通人群中很常见，并且与静脉血栓形成的风险增加相关。APC 抵抗最初在血栓形成倾向的家族中发现，后来发现与常见的 FV Arg506Gln（FV（利登））突变相关，该突变消除了 FV 中的一个 APC 裂解位点。尽管 FV（利登）是遗传性 APC 抵抗的主要原因，但越来越清楚的是，其他一些遗传和获得性条件也导致 APC 抵抗，从而增加静脉血栓形成的风险。本文综述了 APC 抵抗的多因素病因，并讨论了其临床意义。
