De Stefano V, Leone G
Divisione di Ematologia, Università Cattolica, Rome, Italy.
Haematologica. 1995 Jul-Aug;80(4):344-56.
Inherited resistance to activated protein C (APC) was recently recognized as a novel cause underlying venous thrombophilia. In most cases APC-resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Amino acid substitution occurs at one of the APC cleavage sites of factor Va, rendering it resistant to APC inactivation. Plasma anticoagulant response to exogenous APC as a simple diagnostic assay of APC- resistance shows good sensitivity and specificity as compared to gene analysis, yet standardization of the results needs to be improved. The APC-resistance trait is present in 2%-6% of the general population and was found to be associated with venous thrombophilia in about 20% of patients with unexplained thrombosis. Clinical features are substantially similar to other congenital plasma abnormalities predisposing to thrombosis (antithrombin III, protein C, protein S deficiencies); yet the overall clinical penetrance of the defect seems lower, at least for the heterozygous condition. Preliminary data suggest a higher risk of thrombosis in APC-resistant homozygous individuals or in patients exhibiting APC-resistance together with other thrombophilic genetic defects. To date, genetically determined APC-resistance does not seem to play a significant role in the development of arterial thrombotic disease.
遗传性活化蛋白C（APC）抵抗最近被认为是静脉血栓形成倾向的一个新的潜在原因。在大多数情况下，APC抵抗是由于凝血因子V基因中的单个点突变，导致精氨酸506被谷氨酰胺取代（凝血因子V莱顿突变）。氨基酸取代发生在凝血因子Va的一个APC裂解位点，使其对APC失活具有抗性。作为APC抵抗的一种简单诊断检测方法，血浆对外源性APC的抗凝反应与基因分析相比具有良好的敏感性和特异性，但结果的标准化仍需改进。APC抵抗性状在普通人群中的出现率为2%-6%，在约20%原因不明的血栓形成患者中发现与静脉血栓形成倾向有关。临床特征与其他易导致血栓形成的先天性血浆异常（抗凝血酶III、蛋白C、蛋白S缺乏）基本相似；然而，该缺陷的总体临床外显率似乎较低，至少对于杂合子情况是这样。初步数据表明，APC抵抗纯合子个体或同时表现出APC抵抗和其他血栓形成倾向遗传缺陷的患者发生血栓形成的风险更高。迄今为止，基因决定的APC抵抗似乎在动脉血栓性疾病的发生中不起重要作用。
