Pulmonary hypertension in sickle cell disease.

Pulmonary hypertension (PH), a disorder characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, is an increasingly recognized complication of sickle cell disease (SCD), with a prevalence of approximately 30% in adult patients. It confers a high risk of death, with 2-year mortality rates of 40-50%, even at modest elevations of pulmonary pressures. The pathogenesis of PH complicating SCD is probably heterogeneous, including hemolysis and its effect on nitric oxide bioavailability, asplenia, thrombosis, chronic lung disease, and iron overload. Clinical manifestations of PH are difficult to recognize in sickle cell patients as they overlap with signs and symptoms of chronic anemia. Doppler echocardiography is recommended for screening, using tricuspid regurgitant jet velocity (TRV) to estimate pulmonary artery systolic pressure, with PH defined as TRV of at least 2.5 m/s. Detection of an elevated TRV is followed by characterization of PH by various tests to confirm diagnosis, define hemodynamics, identify underlying causes or associated diseases, determine severity and prognosis, and select appropriate therapy. Current data on treatment of PH in SCD are limited. Recommendations include intensification of sickle cell-directed therapies, treatment of causal factors or associated diseases, general supportive measures, and use of PH-specific pharmacologic agents. Further knowledge of the pathobiology of this complication and clinical trials of effective therapy are needed to improve survival.