Pathophysiology and treatment of pulmonary hypertension in sickle cell disease.

Pulmonary hypertension (PH) affects approximately 10% of adult patients with sickle cell disease (SCD), particularly those with the homozygous genotype. An increase in pulmonary artery systolic pressure, estimated noninvasively by echocardiography, helps identify SCD patients at risk for PH but definitive diagnosis requires right heart catheterization. About half of SCD-related PH patients have pre-capillary PH with potential etiologies of 1) an NO deficiency state and vasculopathy consequent to intravascular hemolysis, 2) chronic pulmonary thromboembolism, or 3) upregulated hypoxic responses secondary to anemia, low O2 saturation and microvascular obstruction. The remainder have post-capillary PH secondary to left ventricular dysfunction. Though the pulmonary artery pressure in SCD patients with PH is only moderately elevated, they have a markedly higher risk of death than patients without PH. Guidelines for diagnosis and management of SCD-related PH were published recently by the American Thoracic Society. Management of adults with sickle-related PH is based on anti-coagulation for those with thromboembolism, oxygen therapy for those with low oxygen saturation, treatment of left ventricular failure in those with post-capillary PH, and hydroxyurea or transfusions to raise the hemoglobin concentration, reduce hemolysis, and prevent vaso-occlusive events that cause additional increases in pulmonary pressure. Randomized trials have not identified drugs to lower pulmonary pressure in SCD patients with pre-capillary PH. Patients with hemodynamics of pulmonary arterial hypertension should be referred to specialized centers and considered for treatments known to be effective in other forms of pulmonary arterial hypertension. There have been reports that some of these treatments improve SCD-related PH.