Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state.

The pathogenesis of pulmonary hypertension (PAH), a serious complication in thalassemia, is not well understood. Thromboembolism has been postulated as one of the causative factors; however, there are currently limited specific data on its role. To examine whether increased platelet activation and hypercoagulability are linked to PAH, 25 beta-thalassemia major and beta-thalassemia intermedia patients were evaluated with Doppler echocardiograms for estimation of pulmonary artery pressure and with laboratory assays for indications of a prothrombotic state. The association of clinical variables and abnormal coagulation assays with PAH was determined. PAH was identified in 17 (68%) patients; mean pulmonary artery systolic pressure was 39.8 +/- 5.4 mm Hg. PAH was significantly associated with prior splenectomy, older age, and evidence for chronic hemolysis, diagnosed in both transfused (n = 10) and nontransfused (n = 7) patients. Increased platelet activation, measured by P-selectin, was significantly associated with PAH (P = 0.001). Increased thrombin-antithrombin III level was more prevalent in the presence of PAH, but increased fibrinolysis or low protein C levels were not. This study underscores the role of platelet activation in the development of PAH and stresses its occurrence even among patients who are regularly transfused, especially those who are older and have had splenectomies.