De Stefano V, Chiusolo P, Paciaroni K, Leone G
Department of Hematology, Catholic University, Rome, Italy.
Semin Thromb Hemost. 1998;24(4):367-79. doi: 10.1055/s-2007-996025.
Inherited resistance to activated protein C (APC) has been 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). Factor V Leiden allele is present in about 5% of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is virtually absent in Africans, Asians, and races with Asian ancestry such as Amerindians, Eskimos, and Polynesians; this suggests a single origin of the mutation, which has been proven by haplotype analysis. A low prevalence of the mutation (1%) was noticed in African-Americans for recent racial admixture. Factor V Leiden presents not a major role as risk factor for arterial thrombosis, while it is present in 18% of Caucasian patients with venous thrombosis. This high incidence prevalence mirrors the incidence in the corresponding general populations and can be even higher in some areas according to the ethnic background. Conversely, factor V Leiden is usually not found in non-Caucasian thrombotic patients; this could give reason of the lower incidence of venous thrombotic disease in Africa and Asia in comparison with Europe. Therefore, screening for factor V Leiden is suggested for all Caucasian individuals with previous venous thrombosis; inclusion criteria for the screening should not be stringent because clinical manifestations associated with the mutant genotype can be also mild or secondary to circumstantial risk factors or manifesting at advanced age. Factor V Leiden can act also as concurrent risk factor in individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia. So far, screening for the mutation in individuals with no history of thrombosis is recommended only for relatives of proband patients identified as carriers; the available data do not justify indiscriminate screening before risk situations such as oral contraceptives intake, pregnancy, or high-risk surgery.
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）。凝血因子V莱顿等位基因存在于约5%的白种人个体（欧洲人、犹太人、以色列阿拉伯人和印度人）中，而在非洲人、亚洲人以及具有亚洲血统的种族如美洲印第安人、爱斯基摩人和波利尼西亚人中几乎不存在；这表明该突变有单一的起源，单倍型分析已证实了这一点。由于近期的种族混合，在非裔美国人中该突变的患病率较低（1%）。凝血因子V莱顿突变作为动脉血栓形成的危险因素作用不大，而在18%的白种人静脉血栓形成患者中存在该突变。这种高发病率反映了相应普通人群中的发病率，并且根据种族背景在某些地区可能更高。相反，在非白种人的血栓形成患者中通常找不到凝血因子V莱顿突变；这可以解释为什么与欧洲相比，非洲和亚洲的静脉血栓形成疾病发病率较低。因此，建议对所有既往有静脉血栓形成的白种人进行凝血因子V莱顿突变筛查；筛查的纳入标准不应过于严格，因为与突变基因型相关的临床表现可能也很轻微，或者继发于环境危险因素，或者在老年时才表现出来。凝血因子V莱顿突变在天然抑制剂缺乏或轻度高同型半胱氨酸血症的个体中也可作为并发危险因素。到目前为止，仅建议对被确定为携带者的先证者患者的亲属进行无血栓形成病史个体的突变筛查；现有数据不足以证明在口服避孕药、怀孕或高风险手术等风险情况之前进行无差别筛查是合理的。
