The molecular basis of inherited thrombophilia.
The molecular basis of inherited thrombophilia.
复制标题
遗传性血栓形成倾向的分子基础。
作者：
P. Manucci
尽管几个世纪以来人们都知道，遗传性凝血缺陷会导致终身出血性疾病，但遗传性血栓性疾病的存在却只有几十年的时间。遗传性血栓形成倾向可定义为由遗传决定的静脉血栓栓塞倾向，其特征是在年轻时发生，没有明显的原因，并且倾向于复发。本文综述了遗传性血栓形成倾向的发病率、生化和分子基础，描述了其主要临床表现，并提供了一般的治疗指南。它仅限于更常见和公认的血栓形成倾向的原因：抗凝血酶、蛋白C和蛋白S缺乏;凝血因子V突变引起的对活化蛋白C的抗性;以及因子II（凝血酶原）的功能获得性突变。遗传性血栓形成倾向的其他原因则更为罕见，如异常纤维蛋白原血症，或尚未确定，如纤维蛋白溶解系统（纤溶酶原，富含组氨酸的糖蛋白）和血栓调节蛋白的异常。
Even though it has been known for centuries that inherited defects of blood coagulation cause lifelong bleeding disorders, the existence of the counterpart, inherited thrombotic disorders, has been appreciated for only a few decades. Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism which characteristically occurs at a young age with no apparent cause and tends to recur. This article reviews the prevalence, biochemical and molecular basis of inherited thrombophilia, describes the main clinical manifestations and provides general guidelines for treatment. It is restricted to the more frequent and well-established causes of thrombophilia: antithrombin, protein C and protein S deficiency; resistance to activated protein C caused by mutations in coagulation factor V; and the gain-of-function mutation of factor II (prothrombin). Other causes of inherited thrombophilia are much rarer, such as dysfibrinogenemia, or not firmly established, such as abnormalities of the fibrinolytic system (plasminogen, histidin-rich glycoprotein) and thrombomodulin.