Chronic Hyper-Hemolysis in Sickle Cell Anemia: Association of Vascular Complications and Mortality with Less Frequent Vasoocclusive Pain
Chronic Hyper-Hemolysis in Sickle Cell Anemia: Association of Vascular Complications and Mortality with Less Frequent Vasoocclusive Pain
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DOI：
10.1371/journal.pone.0002095
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发表时间：
2008-05-07
期刊：
影响因子：
3.7
通讯作者：
Steinberg, Martin H.
中科院分区：
文献类型：
--
作者：
Taylor, James G. V., I;Nolan, Vikki G.;Steinberg, Martin H.
背景：镰状细胞性贫血的血管内溶血可导致与一氧化氮缺乏、年龄增长和死亡率增加相关的并发症。我们之前已经报道过，在一小部分患有镰状细胞病的成年人中，强烈的溶血与血管并发症的风险增加有关。这些观察在其他人群中没有得到证实。方法：血清乳酸脱氢酶(LDH)值的分布被用来替代来自镰状细胞病合作研究(CSSCD)的同期患者组和历史成人人群的血管内溶血，这些患者都有镰状细胞性贫血。慢性溶血由LDH最高四分位数定义，并与LDH最低四分位数进行比较。结果：溶血过多的患者有较高的收缩压、小腿溃疡(OR3.27，95%CI1.925.53，P=0.0001)、异常勃起(OR2.62，95%CI1.13~6.90，P=0.03)和肺动脉高压(OR4.32，95%CI2.12~8.60，P<；0.0001)，而骨坏死(OR0.32，95%CI0.19~0.54，P<；)；疼痛(OR0.23，95%CI0.09~0.0001，P=0.0004)较少。溶血过多受胎儿血红蛋白和地中海贫血的影响，是CSSCD人群早期死亡的危险因素(危险比=1.97，P=0.02)。结论：稳态LDH测定可以识别慢性溶血过多表型，包括较少的血管闭塞性疼痛和较早的死亡率。临床医生应该考虑对这些患者进行镰状细胞特异性治疗，就像对那些更频繁的急性疼痛患者所做的那样。研究结果还表明，镰状细胞性贫血中的一类重要的疾病修饰物会影响溶血率。
Background: Intravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations.Methods: The distribution of serum lactic dehydrogenase (LDH) values was used as a surrogate measure of intravascular hemolysis in a contemporaneous patient group and an historical adult population from the Cooperative Study of Sickle Cell Disease (CSSCD), all with sickle cell anemia. Chronic hyper-hemolysis was defined by the top LDH quartile and was compared to the lowest LDH quartile. Results: Hyper-hemolysis subjects had higher systolic blood pressure, higher prevalence of leg ulcers (OR 3.27, 95% CI 1.925.53, P, 0.0001), priapism (OR 2.62, 95% CI 1.13-6.90, P = 0.03) and pulmonary hypertension (OR 4.32, 95% CI 2.12-8.60, P < 0.0001), while osteonecrosis (OR 0.32, 95% CI 0.19-0.54, P < 0.0001) and pain (OR 0.23, 95% CI 0.09-0.55, P = 0.0004) were less prevalent. Hyper-hemolysis was influenced by fetal hemoglobin and a thalassemia, and was a risk factor for early death in the CSSCD population (Hazard Ratio = 1.97, P = 0.02).Conclusions: Steady state LDH measurements can identify a chronic hyper-hemolysis phenotype which includes less frequent vasooclusive pain and earlier mortality. Clinicians should consider sickle cell specific therapies for these patients, as is done for those with more frequent acute pain. The findings also suggest that an important class of disease modifiers in sickle cell anemia affect the rate of hemolysis.