Thalassemia Associated Pulmonary Hypertension

Abstract

Cardiac disease is the main cause of death in both forms of thalassemia; thalassemia major (TM) and thalassemia intermedia (TI). Pulmonary hypertension (PH) is one of the cardiopulmonary morbidities with high mortality that, if not treated, may trigger right-sided heart failure and premature death. PH is defined as a mean pulmonary artery pressure of ≥25 mmHg at rest or ≥30 mmHg during exercise. The prevalence of PH is known to be higher in TI than in TM. Moreover, the pathophysiology of PH in thalassemia appears to be sophisticated and complex. Risk factors for occurrence of PH consists of non-transfusion dependent thalassemia (NTDT), sub-optimally transfused transfusion dependent thalassemia (TDT), splenectomy, thrombocytosis, anemia, NRBC ≥ 300 × 106, iron accumulation, history of thrombosis and older age. Other parameters which aggravate the risk of PH include hemolysis, oxidative stress, hypoxemia, alteration of erythrocyte membrane, decline of nitric oxide biological availability, arginine abnormal regulation and arginase excess. The screening method for PH is Doppler echocardiography but the gold standard for detection of PH is right heart catheterization (RHC). Current medical therapeutic options in PH comprise hydroxyurea, L- Carnitine, sildenafil, calcium channel antagonists, endothelin 1-receptor blockers and prostacyclin agonists. The only curative surgical method for the refractory and severe cases of PH is pulmonary endarterectomy. In this article, the etiology, pathophysiology, diagnostic methods and novel therapies of thalassemia associated PH are discussed.