Frenkel E P, Bick R L
University of Texas Southwestern Medical Center, Dallas, USA.
Semin Thromb Hemost. 1999;25(4):375-86. doi: 10.1055/s-2007-994941.
This article addresses the issue of thromboembolic disorders associated with the prothrombin G20210A gene mutation, with heparin cofactor II (HC-II) defects and with primary (essential) thrombocythemia. The prothrombin gene mutation is of recent discovery, is inherited as an autosomal dominant disorder, and seems to be highly prevalent in the general white population. The incidence is almost as high as that known for factor V Leiden. Both venous and arterial thromboses are noted, especially deep venous thrombosis, including cerebral venous events and myocardial infarction. As with other congenital thrombophilic states, additional risk factors or multiple defects seem to precipitate the events. Although initially elevated plasma prothrombin levels were described in these patients, this is no longer valid for all patients. At this time there is no easy screening test to detect this defect, but, because of the high prevalence, prothrombin G20210A gene mutation should routinely be assayed for in thrombophilic patients. The association between HC-II defects and thromboembolism is more controversial, and reports both confirming and denying this association have been described. The congenital form of HC-II defect is autosomal dominant. HC-II can be determined by its activity and immunologically. HC-II defects very likely play a role in conjunction with other congenital or acquired defects. Acquired HC-II defects are found in association with systemic disseminated intravascular coagulation (DIC) but not with local activation of the hemostasis system. HC-II levels are also decreased in preeclamptic women, and newborns have physiologically low levels. HC-II defects in thrombophilic patients should be considered after the more common disorders have been ruled out. Primary (essential) thrombocythemia can be associated with both thromboembolic events and bleeding. Typical thrombotic manifestations are erythromelalgia and microvascular thrombosis. Also, pregnant females suffer high rates of complications, such as spontaneous abortion. A number of treatment modalities are at present available to not only decrease platelet counts but also manage thromboembolic events.
本文探讨了与凝血酶原G20210A基因突变、肝素辅因子II（HC-II）缺陷以及原发性（特发性）血小板增多症相关的血栓栓塞性疾病问题。凝血酶原基因突变是最近才发现的，作为常染色体显性疾病遗传，在一般白人群体中似乎非常普遍。其发病率几乎与因子V莱顿突变的发病率一样高。静脉和动脉血栓形成均有报道，尤其是深静脉血栓形成，包括脑静脉事件和心肌梗死。与其他先天性血栓形成倾向状态一样，额外的危险因素或多种缺陷似乎会促使这些事件发生。虽然最初在这些患者中描述了血浆凝血酶原水平升高，但现在并非所有患者都是如此。目前没有简单的筛查试验来检测这种缺陷，但由于其高患病率，在血栓形成倾向患者中应常规检测凝血酶原G20210A基因突变。HC-II缺陷与血栓栓塞之间的关联更具争议性，既有证实这种关联的报道，也有否定这种关联的报道。HC-II缺陷的先天性形式是常染色体显性遗传。HC-II可以通过其活性和免疫学方法进行测定。HC-II缺陷很可能与其他先天性或获得性缺陷共同起作用。获得性HC-II缺陷与全身性弥散性血管内凝血（DIC）有关，但与止血系统的局部激活无关。先兆子痫妇女的HC-II水平也会降低，新生儿的HC-II水平在生理上较低。在排除了更常见的疾病后，应考虑血栓形成倾向患者存在HC-II缺陷的可能性。原发性（特发性）血小板增多症可与血栓栓塞事件和出血相关。典型的血栓形成表现为红斑性肢痛症和微血管血栓形成。此外，怀孕女性的并发症发生率很高，如自然流产。目前有多种治疗方法，不仅可以降低血小板计数，还可以处理血栓栓塞事件。
