Pathophysiology of Pulmonary Hypertension in Sickle Cell Disease

The pathophysiology of pulmonary hypertension (PH) in sickle cell disease (SCD) is multifactorial: hemolysis, hypercoagulability, hypoxemia, oxidative stress, platelet activation, increased adhesiveness, inflammatory cell activation and genetic susceptibility, all contributing in varying degrees to endothelial dysfunction. Intravascular hemolysis is the main pathological process contributing to vasculopathy by releasing toxic red blood cell products that impair endothelial function, cause hypercoagulable state and drive oxidative and inflammatory stress. Hemolysis induced nitric oxide imbalance is one the most important contributors to high pulmonary artery pressures seen in SCD. Multi-faceted, targeted interventions, before irreversible vasculopathy develops, will allow for improved patient outcomes and life expectancy, stressing the need for a better understanding of the multiple pathophysiological mechanisms involved in the development of PH before considering those patients for targeted therapies. Hemolysis is still considered as the main contributor of PH in SCD but the mechanisms by which it causes PH are still not completely known. This review precisely presents the various pathophysiological mechanisms and factors that have been proposed till date to help the reader get an overview.