Our studies suggest that secondary pulmonary hypertension is common in adult patients with sickle cell disease, appears to be resistant to hydroxyurea therapy, is linked to hemolysis and is associated with a high mortality. The current study evaluates (1) the pathophysiologic processes that are associated with and potentially contribute to secondary pulmonary hypertension in adult patients with sickle cell anemia. (2) 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 disease. (3) 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) 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. We have enrolled 47 subjects in the clinical trial with 40 completing stage I, 16 completing stage II and 7 completing stage III. Due to the availability of FDA approved oral medications, such as Prostacyclin, Bosentan, Sildenafil and L-Arginine, etc, Stage II of this protocol will only be offered if the oral medications fail or are not tolerated, There have been no adverse events related to the inhalation of nitric oxide and approximately 80% of patients are responding with decreases in pulmonary pressures. The efficacy data accrued to date are currently under analysis for publication. Conclusions: The use of six-minute walk distance to evaluate the effects of therapies such as hydroxyurea, transfusion, and selective pulmonary vasodilator and remodeling agents has the potential to accelerate the development of specific therapies for this population. These results suggest that increased pulmonary vascular resistance is poorly tolerated in patients with severe anemia, potentially explaining the increased mortality associated with its development in this population.
| Anthi, Anastasia; Machado, Roberto F; Jison, Maria L et al. (2007) Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension. Am J Respir Crit Care Med 175:1272-9 |
| Gladwin, Mark T; Sachdev, Vandana; Jison, Maria L et al. (2004) Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 350:886-95 |
