Kato Gregory J, Hsieh Matthew, Machado Roberto, Taylor James, Little Jane, Butman John A, Lehky Tanya, Tisdale John, Gladwin Mark T
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1476, USA.
Am J Hematol. 2006 Jul;81(7):503-10. doi: 10.1002/ajh.20642.
In patients with sickle cell disease, anemia is a recognized risk factor for stroke, death, and the development of pulmonary hypertension. We have proposed that hemolytic anemia results in endothelial dysfunction and vascular instability and can ultimately lead to a proliferative vasculopathy leading to pulmonary hypertension. Consistent with this mechanism of disease, we now report a case series of six patients with obliterative central nervous system vasculopathy who also have pulmonary hypertension and high hemolytic rate. These patients, identified in the course of a prospective screening study for pulmonary hypertension, presented with neurological symptoms prompting neuroimaging studies. Compared to 164 other patients of similar age in the screened population, those with newly diagnosed or clinically active cerebrovascular disease have significantly lower hemoglobin levels and higher levels of lactate dehydrogenase. A review of the literature suggests that many clinical, epidemiological, and physiological features of the arteriopathy of pulmonary hypertension closely overlap with those of stroke in sickle cell disease, both known to involve proliferative vascular intimal and smooth muscle hypertrophy and thrombosis. These cases suggest that cerebrovascular disease and pulmonary hypertension in sickle cell disease share common mechanisms, in particular, reduced nitric oxide bioactivity associated with particularly high-grade hemolysis. Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension.
在镰状细胞病患者中，贫血是公认的中风、死亡及肺动脉高压发生的危险因素。我们提出，溶血性贫血会导致内皮功能障碍和血管不稳定，并最终导致增殖性血管病变，进而引发肺动脉高压。与这种疾病机制一致，我们现在报告一组6例患有闭塞性中枢神经系统血管病变且同时伴有肺动脉高压和高溶血率的病例。这些患者是在一项针对肺动脉高压的前瞻性筛查研究过程中被发现的，他们出现了提示进行神经影像学检查的神经系统症状。与筛查人群中其他164名年龄相仿的患者相比，那些新诊断出或患有临床活动性脑血管疾病的患者血红蛋白水平显著更低，乳酸脱氢酶水平更高。文献综述表明，肺动脉高压性动脉病变的许多临床、流行病学和生理学特征与镰状细胞病中风的特征密切重叠，二者均涉及增殖性血管内膜和平滑肌肥大以及血栓形成。这些病例表明，镰状细胞病中的脑血管疾病和肺动脉高压具有共同机制，尤其是与特别严重的溶血相关的一氧化氮生物活性降低。临床医生应怀疑患有肺动脉高压的镰状细胞病患者存在隐匿性脑血管疾病。
