Hemolytic anemia-associated pulmonary hypertension in sickle cell disease

Pulmonary hypertension is one of the leading causes of death in adult sickle cell patients, with a prevalence of 20% to 40%. Although these patients have lower pulmonary pressures than patients with primary pulmonary hypertension, both groups suffer high 2-year mortality rates. Pulmonary hypertension may go undetected until the disease is advanced. Therefore, all adult patients with sickle cell disease should be screened with transthoracic Doppler echocardiogram and the tricuspid regurgitant jet (TRJ) velocity measured to estimate pulmonary artery pressures. A regurgitant jet (RJ) velocity of 2.5 m/s or higher establishes diagnosis and suggests a high risk of death (rate ratio of 10.1; CI= 2.2-47). Basic and epidemiologic studies suggest that pulmonary hypertension in sickle cell disease is mechanistically linked to chronic hemolytic anemia. Hemolysis results in the release of hemoglobin and arginase from the erythrocyte, increasing the consumption and decreasing the production of nitric oxide (NO), respectively. NO is a critical regulator of vasodilation and vascular homeostasis whose inactivation produces vasoconstriction and proliferative vasculopathy. Finally, we review suggested therapies including the established treatments and new pulmonary vasodilator and remodeling agents in the management of pulmonary hypertension in hemolytic anemias.