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

Abstract

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: ClinicalTrials.gov NCT00081523.

Conflict of interest statement

Conflict of Interest: Nothing to report.

Figures

Figure 1

Hematological and pulmonary response to hydroxyurea therapy in a representative patient. Baseline measurements were obtained, and then following the commencement of hydroxyurea therapy in this 46-year-old woman with sickle cell disease, who was started on bosentan 8 months before beginning hydroxyurea. Following the induction of fetal hemoglobin, linked rises were seen in total blood hemoglobin, (Hgb), and associated fall in absolute reticulocyte count and serum lactate dehydrogenase. An improvement in pulmonary arterial pressure was suggested by a fall in serum probrain natriuretic peptide and tricuspid regurgitant peak velocity (TR peak velocity).