Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea

Am J Hematol. 2009 Aug;84(8):530-32. doi: 10.1002/ajh.21446.


Elevated pulmonary arterial systolic pressure is strongly associated with mortality in patients with sickle cell disease (SCD). A tricuspid regurgitant velocity (TRV) of 2.5 m/s or greater by trans-thoracic echocardiogram is a key marker of risk [–3]. The pathophysiologic mechanism involves release from the red cell during intravascular hemolysis of cell-free plasma hemoglobin and arginase [4]. Hydroxyurea is the only drug approved by the Food and Drug Administrations specifically for SCD. It acts by increasing levels of fetal hemoglobin, which inhibits sickling, and has been shown to reduce the incidence of vaso-occlusive crisis (VOC), and prolong survival in patients with sickle cell disease [5,6]. Because fetal hemoglobin also reduces the rate of hemolysis in SCD, hypothetically, hydroxyurea might also reduce the severity of hemolysis-linked vascular dysfunction and pulmonary hypertension. Herein, we describe five patients with sickle cell disease having elevated pulmonary arterial systolic pressure who exhibited improvement in their baseline laboratory parameters of hemolysis, accompanied by reduced TRV, during treatment with hydroxyurea. Hydroxyurea may have a role in the management of selected patients with elevated TRV.

Trial registration: NCT00081523.

Publication types

  • Clinical Trial
  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anemia, Sickle Cell* / blood
  • Anemia, Sickle Cell* / diagnostic imaging
  • Anemia, Sickle Cell* / drug therapy
  • Anemia, Sickle Cell* / mortality
  • Anemia, Sickle Cell* / physiopathology
  • Antisickling Agents / administration & dosage*
  • Arginase / blood
  • Blood Pressure / drug effects*
  • Disease-Free Survival
  • Echocardiography / methods
  • Female
  • Fetal Hemoglobin / analysis
  • Hemolysis / drug effects*
  • Humans
  • Hydroxyurea / administration & dosage*
  • Male
  • Pulmonary Artery / physiopathology*
  • Survival Rate
  • Vascular Diseases / blood
  • Vascular Diseases / diagnostic imaging
  • Vascular Diseases / drug therapy
  • Vascular Diseases / mortality
  • Vascular Diseases / physiopathology


  • Antisickling Agents
  • Fetal Hemoglobin
  • Arginase
  • Hydroxyurea

Associated data