Intravascular Hemolysis, Vascular Endothelial Cell Activation and Thrombophilia in Splenectomized Patients with Hemoglobin E/β-Thalassemia Disease

Abstract

The relationship between asplenia and thrombophilia in β-thalassemia disease patients is not yet completely understood. One hundred and ten adult hemoglobin (Hb) E/β-thalassemia (E/β-Thal) disease outpatients, dichotomized according to the presence or absence of the spleen, were prospectively studied for evidence of intravascular hemolysis (IVH) and vascular endothelial cell (EC) activation. Biomarkers of IVH (serum cell-free Hb), EC [soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1)], platelet and EC [soluble P-selectin (sP-selectin)], inflammation [high-sensitivity C-reactive protein (hs-CRP)], and coagulation [thrombin-antithrombin complexes (TAT)] activation, as well as other selected blood tests were determined. The 61 splenectomized patients had a more severe hemolytic disease and higher levels of cell-free Hb and ferritin (p = 0.003), sE-selectin, sP-selectin, hs-CRP, and TAT (p < 0.05). However, serum levels of sVCAM-1 were not different between the two groups. The findings suggested IVH and EC activation. Together with chronic iron overload and chronic low-grade inflammation activation, the findings extend our understanding of the mechanism of thrombophilia in splenectomized E/β-Thal disease patients.

Intravascular Hemolysis: A Disease Mechanism Not to Be Ignored

“…As such, the report by Atichartakarn et al [5], in association with others [6,7], provides data to indicate that splenectomy in thalassemia and HS, respectively, may have important pathophysiological consequences related to the induction, or prevention, of IVH, respectively (fig. 1).…”

“…A number of risks and complications are reported to be associated with splenectomy, including an increased risk of infection and venous thromboembolism [1,4]. In this issue of Acta Haematologica, Atichartakarn et al [5 ]report important data to indicate that, following splenectomy, hemoglobin E/β-thalassemia individuals present a significant increase in IVH (as indicated by elevated circulating levels of cell-free hemoglobin), in association with alterations in markers consistent with inflammation, endothelial activation and hypercoagulability. Authors suggest that such IVH could participate in the thrombophilia that has been observed in postsplenectomized thalassemia.…”

“…Splenectomy is also employed to reduce EVH in HS, and a recent publication demonstrated that, in contrast to the observations of Atichartakarn et al [5] in thalassemia, IVH appears to be significantly reduced by splenectomy in HS patients, in association with reductions in reticulocytosis, red cell-adhesive properties and inflammation [7]. Splenectomy was also associated with increased leukocyte and platelet counts in these patients [7].…”

“…Whether a decease or an increase in the incidence of PH occurs in splenectomized HS is unclear, but a recent report has found no significant elevation in tricuspid regurgitant jet velocity in HS individuals despite a median 25-year interval since splenectomy [8,9]. Animal experiments indicate that splenectomy can cause leukocytosis and increased platelet counts [10], as observed in both the thalassemia patients and HS patients of these reports, following splenectomy [5,7]. …”

Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

“…A splenectomy is performed to reduce the risk of spleen-induced extravascular hemolysis in patients exhibiting signs of hypersplenism, which increases blood transfusion requirements (9). A previous study reported increased levels of serum cell-free Hb, which provides evidence of intravascular hemolysis (10). …”