Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Hematol. 2008 Jan;83(1):6-14.

Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease.

Author information

  • 1Vascular Medicine Branch, NHLBI, NIH, Bethesda, Maryland 20892-1476, USA. jamesta@mail.nih.gov

Abstract

Pulmonary hypertension is a common complication of sickle cell disease (SCD) and a risk factor for early death. Hemolysis may participate in its pathogenesis by limiting nitric oxide (NO) bioavailability and producing vasculopathy. We hypothesized that hemoglobin mutations that diminish hemolysis in SCD would influence pulmonary hypertension susceptibility. Surprisingly, coincident alpha-thalassemia (Odds Ratio [OR]=0.95, 95% CI=0.46-1.94, P=NS) was not associated with pulmonary hypertension susceptibility in homozygous SCD. However, pulmonary hypertension cases were less likely to have hemoglobin SC (OR=0.18, 95% confidence interval [CI]=0.06-0.51, P=0.0005) or Sbeta(+) thalassemia (OR=0.25, 95% CI=0.06-1.16, P=0.10). These compound heterozygotes may be protected from pulmonary hypertension because of reduced levels of intravascular hemolysis, but develop this complication at a lower rate possibly due to the presence of non-hemolytic risk factors such as renal dysfunction, iron overload and advancing age. Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio=8.20, P=0.0057).

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk