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

INCLUSION CRITERIA For Stage I for Pulmonary Hypertension Subjects: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-halassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Mild to severe pulmonary hypertension with systolic pulmonary artery pressures greater than or equal to 30 mm Hg (tricuspid regurgitant velocity greater than 2.5 m/sec, assuming right atrial pressure greater than 5 cm H20) or right ventricular enlargement. We will compare these studies to a control group of sickle cell patients that do not have pulmonary hypertension. For Stage I Controls: Males or females, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-halassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Tricuspid regurgitant velocity less than or equal to 2.4 m/sec, matched for age, gender, hydroxyurea therapy status and fetal hemoglobin levels with the pulmonary hypertension subjects. For Stage II: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-thalassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Mild to severe pulmonary hypertension with systolic pulmonary artery pressures greater than or equal to 30 mm Hg (tricuspid regurgitant velocity greater than 2.5 m/sec, assuming right atrial pressure greater than 5 cm H20) or right ventricular enlargement. For Stage III: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-thalassemia genotype is required). Hematocrit greater than 18 % (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Able to walk at least 100 m in six minutes at baseline. Mild to severe pulmonary hypertension with mean pulmonary artery pressures greater than or equal to 25 mm Hg, measured by pulmonary artery catheterization. Pulmonary artery wedge pressure or left ventricular end-diastolic pressure less than or equal to 18 mm Hg or echocardiographic criteria to exclude left ventricular dysfunction. EXCLUSION CRITERIA For Stage I Current pregnancy or lactation For Stage II Current pregnancy or lactation Any of the following medical conditions: Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30% of normal; Stroke within the last six weeks; New diagnosis of pulmonary embolism within the last three months; History of retinal detachment. Hematocrit less than 18 % will not be eligible for the study; may return for evaluation at a later date. Patients taking prostacyclin (inhaled or intravenous) will be excluded from the study. Patients taking calcium channel blockers will be allowed to participate provided they are on a stable dose for greater than one month. For Stage III Current pregnancy or lactation Any of the following medical conditions: Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal; Stroke within the last six weeks; Left ventricular end-diastolic pressure greater than or equal to 18 mm Hg (determined by the pulmonary artery occlusion pressure) or echocardiographic criteria for left ventricular dysfunction; New diagnosis of pulmonary embolism within the last three months; History of retinal detachment; Hematocrit less than 18 % will not be eligible for the study; may return for evaluation at a later date. Patients taking prostacyclin (inhaled or intravenous) will be excluded from the study. Patients taking calcium channel blockers will be allowed to participate provided they are on a stable dose for greater than one month. Patients who are in other research studies for the treatment of pulmonary hypertension or who are on treatment specific for pulmonary hypertension will be excluded from stage III of this study.