Platt O S, Brambilla D J, Rosse W F, Milner P F, Castro O, Steinberg M H, Klug P P
Department of Medicine, Children's Hospital, Boston, MA 02115.
N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.
Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-beta-thalassemias) is needed to counsel patients, target therapy, and design clinical trials.
We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years.
Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death.
Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy.
为了向镰状细胞病（镰状细胞贫血、镰状细胞 - 血红蛋白C病以及镰状细胞 - β地中海贫血）患者提供咨询、确定治疗靶点并设计临床试验，需要了解患者的预期寿命及早期死亡的危险因素。
我们对3764例年龄从出生到入组时66岁的患者进行随访，以确定预期寿命并计算死亡年龄中位数。此外，我们调查了研究期间死亡的所有209例成年患者的死亡情况，并使用比例风险回归分析确定了964例接受至少两年随访的镰状细胞贫血成年患者早期死亡的危险因素。
在镰状细胞贫血（镰状血红蛋白纯合子）儿童和成人中，男性死亡年龄中位数为42岁，女性为48岁。在镰状细胞 - 血红蛋白C病患者中，男性死亡年龄中位数为60岁，女性为68岁。在成年镰状细胞病患者中，18%的死亡发生在有明显器官衰竭的患者中，主要是肾脏衰竭。33%的患者临床上无器官衰竭，但在急性镰状细胞危象期间死亡（78%有疼痛、胸部综合征或两者皆有；22%有中风）。模型显示，在镰状细胞贫血患者中，急性胸部综合征、肾衰竭、癫痫发作、基线白细胞计数高于每立方毫米15000个细胞以及胎儿血红蛋白水平低与早期死亡风险增加相关。
50%的镰状细胞贫血患者存活至50岁以后。很大一部分死亡患者没有明显的慢性器官衰竭，但在疼痛、胸部综合征或中风的急性发作期间死亡。早期死亡率在有症状的患者中最高。高水平的胎儿血红蛋白预示着生存率提高，可能是成年预期寿命的可靠儿童期预测指标。
