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. This study evaluated (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 enrolled 60 subjects in the clinical trial with 50 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 was only offered if the oral medications failed or were not tolerated, There were no adverse events related to the inhalation of nitric oxide and approximately 80% of patients responded 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. This protocol is now closed for accrual and is only open for data and sample analysis.
| Nguyen, Kim-Lien; Tian, Xin; Alam, Shoaib et al. (2016) Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease. Haematologica 101:e40-3 |
| Mehari, Alem; Alam, Shoaib; Tian, Xin et al. (2013) Hemodynamic predictors of mortality in adults with sickle cell disease. Am J Respir Crit Care Med 187:840-7 |
| Mehari, Alem; Gladwin, Mark T; Tian, Xin et al. (2012) Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA 307:1254-6 |
