März W, Nauck M, Wieland H
Department of Medicine, Albert-Ludwigs-University, Freiburg im Breisgau, Germany.
Z Kardiol. 2000 Jul;89(7):575-86. doi: 10.1007/s003920070206.
Venous Thromboembolism develops as the result of multiple interactions between non-genetic and genetic risk factors. The most important non-genetic risk factors are age, tissue damage, oral contraception, pregnancy, obesity and lack of physical activity. Inborn factors predisposing to thrombosis are present in the majority of patients. These comprise defects affecting the anticoagulant pathways of blood coagulation like antithrombin III, protein C and protein S. Together these defects are found in 15-20% of thrombophilia families. The relatively rare defects of antithrombin III, protein C and protein S stand in contrast to two common genetic polymorphisms of procoagulant molecules, factor V-Leiden, the most frequent cause for resistance to activated protein C, and the prothrombin 20210 A allele. Together, these anomalies are found in almost two third of the thrombophilia families. The identification of factor FV-Leiden and prothrombin 20210 A has allowed to examine in detail interactions between genetic and non-genetic risk factors of thromboembolism. The results of these studies indicate that many symptomatic individuals are endowed with more than one (genetic and/or environmental) risk factor. Thrombophilia thus represents an oligogenetic rather than monogenetic clinical phenotype, the expression of which is amplified by circumstantial risk factors. As a consequence of the "multiple hit" concept, the laboratory screening of thrombosis patients needs to include all of the known genetic risk factors even if the "clinical" situation seemingly provides sufficient "explanation" for a thrombotic event.
静脉血栓栓塞症是由非遗传和遗传风险因素之间的多种相互作用导致的。最重要的非遗传风险因素包括年龄、组织损伤、口服避孕药、怀孕、肥胖和缺乏体育活动。大多数患者存在易导致血栓形成的先天因素。这些因素包括影响血液凝固抗凝途径的缺陷，如抗凝血酶III、蛋白C和蛋白S。在15%至20%的血栓形成倾向家族中可发现这些缺陷共同存在。抗凝血酶III、蛋白C和蛋白S相对罕见的缺陷与促凝血分子的两种常见基因多态性形成对比，即因子V-Leiden（对活化蛋白C抵抗的最常见原因）和凝血酶原20210 A等位基因。在几乎三分之二的血栓形成倾向家族中可发现这些异常共同存在。因子FV-Leiden和凝血酶原20210 A的鉴定使得能够详细研究血栓栓塞的遗传和非遗传风险因素之间的相互作用。这些研究结果表明，许多有症状的个体具有不止一种（遗传和/或环境）风险因素。因此，血栓形成倾向代表一种多基因而非单基因的临床表型，其表达会因环境风险因素而放大。由于“多重打击”概念，对血栓形成患者的实验室筛查需要包括所有已知的遗传风险因素，即使“临床”情况似乎为血栓形成事件提供了足够的“解释”。
