Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Anemia

Pulmonary hypertension develops in most forms of hereditary and chronic hemolytic anemia, including sickle cell disease, thalassemia, hereditary spherocytosis, and paroxysmal nocturnal hemoglobinuria, suggesting that there is a clinical syndrome of hemolysis-associated pulmonary hypertension. Retrospective studies from tertiary care referral centers suggest a prevalence of pulmonary hypertension in adults with sickle cell disease ranging from 20 to 40%. Despite the fact the elevations in pulmonary artery pressures are slight, morbidity and mortality are high. In adult sickle cell anemia patients, pulmonary hypertension is emerging as a major risk factor for death. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 80 consecutive patients (20 men and 60 women; mean [±SD] age, 30 ± 10.8 years) between 1/20/2006 and 1/20/2008. The genotype on the basis of hematologic and hemoglobin characteristics was hemoglobin SS in all patients. Pulmonary hypertension was prospectively defined as a tricuspid regurgitant Jet velocity (TFJV) of at least 2.5 m per second. Patients were followed for a mean of 18 months (6–24 months), and data were censored at the time of death or loss to follow-up. Doppler-defined pulmonary hypertension occurred in 37.5 percent of patients (30/80). Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified age, female sex, deferasirox therapy, left ventricular mass index, pulmonary artery systolic pressure, reticulocytes, white-cell count, platelet count, lactate dehydrogenase (a marker of hemolysis), blood urea nitrogen, creatinine, uric acid and self-reported history of cardiovascular complication, billiary stones, retinopathy and acute chest syndrome, as significant independent correlates of pulmonary hypertension. The hemoglobin level, fetal hemoglobin level, hydroxyurea therapy and serum ferritin level were unrelated to pulmonary hypertension. Hazard rate for death according to the TFJV of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was associated with an increased risk of death (0.00 versus 2.54; P=0.998). Mortality rate in 24 months was 6.7% (2/30) for patients with TRJ velocity ≥ 2.5 m/sec versus 0.0% (0/50) for patients without pulmonary hypertension. Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Large trials evaluating the effects of treatment for pulmonary hypertension in the sickle cell anemia population are indicated.