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

Abstract

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.

Review of the Association between Splenectomy and Chronic Thromboembolic Pulmonary Hypertension

“…Some studies regarding certain conditions did not show a link (e.g., hemoglobin H disease, hereditary spherocytosis, idiopathic thrombocytopenic purpura) or reported conflicting results (thalassemia) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, many of these studies involved a smaller number of subjects and used noninvasive means to screen for pulmonary hypertension, mainly echocardiography.…”

“…The contribution of post-splenectomy thrombocytosis to the observed propensity for coagulation is controversial (6,8,20,36,42,89,106,107). Thrombocytosis is not necessary to develop thromboembolic complications after splenectomy and alone does not explain the procoagulant state (24,27,32,89).…”

“…(4)Post-splenectomy thrombocytosis and increased platelet reactivity may promote clot formation(6,66,109). (5) Hemolysis releases the enzyme arginase I into the bloodstream, which competes with the endothelial NO synthetase for arginine, a substrate for NO synthesis(65).…”

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

“…These events lead to an imbalance of vasodilator and vasoconstrictor autacoids; for example, NO and prostacyclin vasodilators decrease, while endothelin-1 vasoconstrictor increases (169,196). Thalassemia patients with pulmonary hypertension have increased markers of endothelial cell activation (endothelin-1), platelet activation (sCD40 L), and hemolysis (lactate dehydrogenase and cell-free Hb) (169).…”

“…These events lead to an imbalance of vasodilator and vasoconstrictor autacoids; for example, NO and prostacyclin vasodilators decrease, while endothelin-1 vasoconstrictor increases (169,196). Thalassemia patients with pulmonary hypertension have increased markers of endothelial cell activation (endothelin-1), platelet activation (sCD40 L), and hemolysis (lactate dehydrogenase and cell-free Hb) (169). Most pulmonary hypertension in thalassemia is precapillary pulmonary hypertension (pulmonary arterial hypertension) with the prevalence of 4.8% and 1.1% in b-thalassemia intermedia and b-thalassemia major, respectively (49).…”