To determine if pulmonary hypertension (PH) is associated with increased mortality in children with sickle-cell disease (SCD), we prospectively followed 88 pediatric patients for a mean of 3 years after echocardiographic screening for PH. Subjects (45 males, 43 females) were 5–20 years old (median 13) at initial screening and included 59 SS, 23 SC, 4 S/β0Thalassemia, 1 S/β+Thalassemia and 1 S/HPFH. PH was defined as tricuscipid regurgitant jet velocity (TRV) of ³2.5 m/s. Of the 88 subjects, 18 (20%) had TRV ³2.5 m/s (median 2.6, range 2.5–3.1). Subjects with PH ranged from 7 to 19 years old (median 15), were predominantly male (12 of 18) and included 14 (78%) SS, 2 SC, 2 S/β0Thalassemia. After a mean follow-up of 36.3 ± 9.4 (SD) months, all 18 patients with PH were alive. None had received specific treatment for PH; one had undergone a successful bone marrow transplant from a matched sibling donor. After a mean follow-up of 33.5 ± 13.3 months, 67 subjects with normal TRV were alive; 3 had been lost to follow-up. To compare risk factors for PH in our children with those reported for adults, we reviewed the clinical data for our subjects. Children with PH had significantly increased serum lactate dehydrogenase (LDH; P=0.04), higher platelet count (P=0.02), and, in males, a history of priapism (P=0.009). No significant differences were observed with respect to age, gender, sickle-cell type, white blood cell count, hemoglobin, reticulocyte count, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, ferritin, history of painful crisis, acute chest syndrome, asthma, splenectomy, or hydroxyurea therapy. To further examine the association of PH and hemolysis, a subanalysis was done excluding 18 chronically transfused patients because transfusion can alter laboratory indicators of hemolysis. Independent variables with P≤0.1 on univariate analysis (LDH, female gender, and platelet count) were entered into a logistic regression model. Only LDH was independently associated with PH (Odds Ratio=1.6, 95% CI=1.2–2.1, P=0.004). Our results show that PH diagnosed by Doppler echocardiography was not associated with an increased risk of death in children with SCD followed for a mean of 3 years. A greatly increased risk of death (rate ratio, 10.1) has been reported in adults followed for a mean of 1.5 years (

N Eng J Med 2004;350:886–95
). In our children, as in the adults, increased LDH, a marker of hemolysis, and, in males, a history of priapism were associated with PH. By contrast, our children with PH did not have increases in serum creatinine, direct bilirubin, alkaline phosphatase and ferritin that have been linked epidemiologically to PH in adults with SCD (
Pediatr Hematol Onc 2007;24:159–70
). These findings suggest that PH of itself may not be a direct cause of death in SCD. Rather, PH may be a manifestation of progressive, cumulative organ damage resulting from chronic hemolysis and systemic vasculopathy that ultimately leads to increased mortality in adulthood. Early recognition and preventive therapy for increased hemolysis may be needed to avert premature death in adults with SCD.

Topics:
death of child, pulmonary hypertension, sickle cell anemia, thalassemia, alkaline phosphatase, ferritin, follow-up, priapism, screening, acute chest syndrome

Disclosures: Berman Rosenzweig:Actelion: Research Funding; Gilead Sciences: Research Funding; United Therapeutics: Research Funding. Barst:Actelion: Consultancy; Eli Lilly: Consultancy; GSK: Consultancy; Gilead : Consultancy; Pfizer: Consultancy.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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