Dahlbäck Björn
Department of Laboratory Medicine, Section of Clinical Chemistry, Lund University, University Hospital Malmö, Malmö, Sweden.
Blood. 2008 Jul 1;112(1):19-27. doi: 10.1182/blood-2008-01-077909.
Venous thromboembolism is a major medical problem, annually affecting 1 in 1000 individuals. It is a typical multifactorial disease, involving both genetic and circumstantial risk factors that affect a delicate balance between procoagulant and anticoagulant forces. In the last 50 years, the molecular basis of blood coagulation and the anticoagulant systems that control it have been elucidated. This has laid the foundation for discoveries of both common and rare genetic traits that tip the natural balance in favor of coagulation, with a resulting lifelong increased risk of venous thrombosis. Multiple mutations in the genes for anticoagulant proteins such as antithrombin, protein C, and protein S have been identified and constitute important risk factors. Two single mutations in the genes for coagulation factor V (FV Leiden) and prothrombin (20210G>A), resulting from approximately 20,000-year-old mutations with subsequent founder effects, are common in the general population and constitute major genetic risk factors for thrombosis. In celebration of the 50-year anniversary of the American Society of Hematology, this invited review highlights discoveries that have contributed to our present understanding of the systems that control blood coagulation and the genetic factors that are involved in the pathogenesis of venous thrombosis.
静脉血栓栓塞是一个重大的医学问题，每年影响千分之一的人。它是一种典型的多因素疾病，涉及遗传和环境风险因素，这些因素影响促凝和抗凝力量之间的微妙平衡。在过去的50年里，血液凝固的分子基础以及控制它的抗凝系统已经被阐明。这为发现常见和罕见的遗传特征奠定了基础，这些特征使自然平衡倾向于凝血，从而导致终身静脉血栓形成风险增加。已经鉴定出抗凝血蛋白（如抗凝血酶、蛋白C和蛋白S）基因中的多个突变，它们构成重要的风险因素。凝血因子V（FV Leiden）和凝血酶原（20210G>A）基因中的两个单突变，源于约2万年前的突变及随后的奠基者效应，在普通人群中很常见，是血栓形成的主要遗传风险因素。为庆祝美国血液学会成立50周年，这篇特邀综述重点介绍了一些发现，这些发现有助于我们目前对控制血液凝固的系统以及参与静脉血栓形成发病机制的遗传因素的理解。
