Nitric Oxide and Transfusion Therapy for Sickle Cell Patients With Pulmonary Hypertension

Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Pulmonary hypertension has now been identified as a major cause of death in adults with sickle cell disease. Inhaled nitric oxide (NO) has been proposed as a possible therapy for both primary and secondary pulmonary hypertension. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia. In addition, chronic exchange transfusion therapy may reduce the progression and/or severity of pulmonary hypertension in these patients. This clinical trial is designed (1) to determine the pathophysiologic processes that are associated with and potentially contribute to secondary pulmonary hypertension in adult patients with sickle cell anemia, by comparing the cardio-pulmonary status of patients with sickle cell disease with and without pulmonary hypertension (2) to determine the relative acute vasodilatory effects of oxygen, intravenous prostacyclin, and inhaled nitric oxide on pulmonary artery pressures and other hemodynamic parameters in patients with secondary pulmonary hypertension and sickle cell anemia, (3) to determine the effects of two months of inhaled nitric oxide on pulmonary artery pressures, other hemodynamic parameters, exercise tolerance, and symptoms in this patient population, and (4) to determine the effects of three months of exchange transfusion on pulmonary artery pressures, other hemodynamic parameters, exercise tolerance, and symptoms in patients who do not receive or fail to respond to NO therapy.