Elevated tricuspid regurgitant jet velocity in sub-groups of thalassemia patients: insight into pathophysiology and the effect of splenectomy

A high tricuspid regurgitant jet velocity (TRV) signifying risk for or established pulmonary hypertension (PH) is a serious complication in thalassemia patients. The underlying pathophysiology in thalassemia sub-groups and potential biomarkers for early detection and monitoring are not well defined, in particular as they relate to spleen removal. To better understand some of these unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25 splenectomized non-thalassemia patients and 12 healthy controls. An elevated TRV (>2.5m/sec) was found in 25/76 (33%) of the patients, confined to non-transfused or those with a late start of transfusions, including patients with hemoglobin H-constant spring, a finding not previously described. These non, or late-transfused patients (76% splenectomized) had significantly increased platelet activation (sCD40L), high platelet count, endothelial activation (endothelin-1) and hemolysis (LDH, plasma free-Hb), while hypercoaguable and inflammatory markers were not significantly increased. The same markers were increased in the 7 patients with confirmed PH on cardiac catheterization, suggesting their possible role for screening patients at risk for PH. A combination of hemolysis and absence of spleen is necessary for developing a high TRV, as neither chronic hemolysis in the non-splenectomized thalassemia patients, nor splenectomy without hemolysis, in the non-thalassemia patients, resulted in an increase in TRV.