Zimmerman S A, Ware R E
Duke-UNC Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Hematol. 1998 Dec;59(4):267-72. doi: 10.1002/(sici)1096-8652(199812)59:4<267::aid-ajh1>3.0.co;2-w.
Thrombosis may play an important role in the pathophysiology of certain complications of sickle cell disease (SCD), including stroke and avascular necrosis (AVN). Currently there is no laboratory or clinical parameter that can identify patients who are at highest risk of developing these thrombotic complications. We hypothesized that some patients with SCD have an inherited hypercoagulable state that results in an increased risk of developing stroke or AVN. We examined the role of two common inherited thrombophilic mutations that, in other populations, have been associated with arterial and venous thrombosis and are amenable to screening with DNA restriction enzyme analysis. The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the C1565T mutation in the platelet glycoprotein IIIa (GPIIIa) gene were evaluated. We analyzed genomic DNA from 86 children and adults with SCD, including 16 patients with a history of a clinical stroke and 14 patients with AVN, for the presence of these mutations. The C677T MTHFR mutation was found in 19% of patients with stroke, 14% of patients with AVN, and 14% of patients with neither complication (P = NS). The C1565T GPIIIa mutation was found in 25% of patients with stroke, 14% of patients with AVN, and 18% of patients with neither complication (P = NS). Although each of these mutations is relatively common in patients with SCD, neither is independently associated with an increased risk of developing stroke or AVN.
血栓形成可能在镰状细胞病（SCD）某些并发症的病理生理学中起重要作用，包括中风和无血管性坏死（AVN）。目前尚无实验室或临床参数能够识别发生这些血栓性并发症风险最高的患者。我们推测，一些SCD患者存在遗传性高凝状态，这会增加发生中风或AVN的风险。我们研究了两种常见的遗传性血栓形成倾向突变的作用，在其他人群中，这些突变与动脉和静脉血栓形成有关，并且可以通过DNA限制性酶切分析进行筛查。评估了亚甲基四氢叶酸还原酶（MTHFR）基因中的C677T突变和血小板糖蛋白IIIa（GPIIIa）基因中的C1565T突变。我们分析了86例SCD儿童和成人的基因组DNA，包括16例有临床中风病史的患者和14例患有AVN的患者，以检测这些突变的存在。在19%的中风患者、14%的AVN患者和14%无并发症的患者中发现了C677T MTHFR突变（P=无显著性差异）。在25%的中风患者、14%的AVN患者和18%无并发症的患者中发现了C1565T GPIIIa突变（P=无显著性差异）。虽然这些突变在SCD患者中都相对常见，但两者均与发生中风或AVN的风险增加无独立关联。
