Pulmonary hypertension in children with hemolytic disorders

Pulmonary hypertension (PH) is an insidious and potentially devastating complication in adults with hemolytic disorders, with pathophysiologic changes starting in childhood. Hemolysis predisposes to PH through nitric oxide depletion from extracellular release of hemoglobin and arginase, and through red blood cell membrane alterations and formation of microparticles, all promoting oxidative damage, vasoconstriction, inflammation, vascular remodeling, and thromboembolic state. PH is best diagnosed by right heart catheterization, though screening often utilizes Doppler echocardiographic measurement of tricuspid regurgitant velocity, and functional assessment by six minute walk test. Understanding the pathophysiology and clinical presentation of PH in sickle cell disease, thalassemias, paroxysmal nocturnal hemoglobinuria, and other hemolytic disorders can improve recognition, evaluation, and management of this condition.