Pulmonary hypertension in thalassemia.
Pulmonary hypertension (PH) is common in thalassemia and contributes to mortality. Advancing age and a history of splenectomy are major risk factors in this population. The etiology of PH is multifactorial, involving a complex interaction of platelets, the coagulation system, erythrocytes, and endothelial cells along with inflammatory and vascular mediators. The long-term effect of splenectomy, red cell membrane pathology, coagulation abnormalities, low nitric oxide (NO) bioavailability, excess arginase activity, platelet activation, oxidative stress, iron overload, and chronic hemolysis play a role. The process of hemolysis disables the arginine-NO pathway through the simultaneous release of erythrocyte arginase and cell-free hemoglobin. Both NO and its obligate substrate arginine are rapidly consumed. The biological consequences of hemolysis on NO bioavailability ultimately translate into the clinical manifestations of PH. Guidelines for the management of PH in thalassemia have not yet been established; however, clinical trials are ongoing in an effort to guide future therapy.
Morris
Claudia R
CR
Department of Emergency Medicine, Children's Hospital and Research Center Oakland, Oakland, California, USA. claudiamorris@comcast.net
Vichinsky
Elliott P
EP
D000328:Adult; D002648:Child; D017408:Guidelines as Topic; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D013789:Thalassemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology