Wong Chieh L, Szydlo Richard, Gibbs Simon, Laffan Mike
Haematology Department, Hammersmith Hospital, Imperial College Academic Health Science Centre, London, UK.
Blood Coagul Fibrinolysis. 2010 Apr;21(3):201-6. doi: 10.1097/MBC.0b013e328331e664.
The role of thrombosis and hereditary thrombotic risk factors in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) and non-CTEPH is not clear. We retrospectively analyzed the frequency of hereditary and acquired thrombotic risk factors in 245 patients with pulmonary hypertension, of whom 45 had CTEPH and 200 had non-CTEPH. Nine of 31 (29%) white patients with CTEPH versus 10 of 129 (7.8%) patients with non-CTEPH were heterozygous for factor V Leiden (FVL; P = 0.001). Contrary to other studies, antiphospholipid antibodies (APA) were not increased. Elevated factor VIII (FVIII) and von Willebrand factor (VWF; >1.5 U/ml) were common in CTEPH and non-CTEPH, although significantly higher (P = 0.01 for FVIII and 0.009 for VWF) in CTEPH versus non-CTEPH. There was no correlation between FVIII-VWF and fibrinogen levels in the CTEPH group (P = 0.84 for FVIII and 0.49 for VWF) but a strong correlation between FVIII-VWF and fibrinogen in the non-CTEPH (P < 0.0001). There was no association between FVIII-VWF and WHO functional status in the CTEPH group although there was a strong correlation (P < 0.001) between the two parameters in the non-CTEPH group. For equivalent WHO functional class, FVIII levels were significantly higher (P = 0.007) in the CTEPH group. We have found no association between FVIII-VWF levels and oxygen saturation in both groups of patients. The results indicate different pathophysiologies for CTEPH and non-CTEPH. The elevation of FVIII and increased incidence of FVL gene polymorphisms in the CTEPH group support a primary role of thrombosis in aetiology.
血栓形成及遗传性血栓形成危险因素在慢性血栓栓塞性肺动脉高压（CTEPH）和非CTEPH发病机制中的作用尚不清楚。我们回顾性分析了245例肺动脉高压患者中遗传性和获得性血栓形成危险因素的发生频率，其中45例患有CTEPH，200例患有非CTEPH。31例白人CTEPH患者中有9例（29%）与129例非CTEPH患者中有10例（7.8%）为因子V莱顿（FVL）杂合子（P = 0.001）。与其他研究相反，抗磷脂抗体（APA）并未增加。CTEPH和非CTEPH患者中因子VIII（FVIII）和血管性血友病因子（VWF；>1.5 U/ml）升高较为常见，尽管CTEPH患者中的水平显著高于非CTEPH患者（FVIII为P = 0.01，VWF为P = 0.009）。CTEPH组中FVIII-VWF与纤维蛋白原水平之间无相关性（FVIII为P = 0.84，VWF为P = 0.49），但非CTEPH组中FVIII-VWF与纤维蛋白原之间存在强相关性（P < 0.0001）。CTEPH组中FVIII-VWF与世界卫生组织（WHO）功能状态之间无关联，而非CTEPH组中这两个参数之间存在强相关性（P < 0.001）。对于同等的WHO功能分级，CTEPH组中的FVIII水平显著更高（P = 0.007）。我们发现两组患者的FVIII-VWF水平与血氧饱和度之间均无关联。结果表明CTEPH和非CTEPH具有不同的病理生理学机制。CTEPH组中FVIII升高及FVL基因多态性发生率增加支持血栓形成在病因学中的主要作用。
