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Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia

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Abstract

Hyperhemolysis syndrome (HHS) is characterized by severe intravascular hemolysis with a decrease in the reticulocyte count, which is triggered and aggravated by transfusion and cannot be explained by standard immunohematological studies. A nationwide study was conducted in order to retrospectively identify thalassemia patients with HHS in Spain in order to assess pre-disposing mechanisms for this syndrome. For this, the expression of adhesion (CD49, CD36) and complement-related molecules (C3a, CD59) and the levels of reticulocyte apoptosis and macrophage activation were measured in 4 thalassemia patients with HHS, 14 patients without HHS, and 10 healthy subjects. Five of the six thalassemia patients had δβ-thalassemia. The patients were not alloimmunized prior to the syndrome, which was developed after the first transfusion in all but one case. Patients with δβ-thalassemia did not respond to corticoids or immunoglobulins; only splenectomy was successful. The expression of CD49 (α4β1 integrin) was far higher in patients who had experienced HHS (85.07 ± 18.46 vs. 46.28 ± 24.31; p < 0.01), and the difference remained significant after correcting by the number of molecules analyzed (Bonferroni p < 0.05). In our population, δβ-thalassemia was the most common hemoglobinopathy in patients with HHS. Furthermore, the risk to develop this syndrome may be associated with an increased expression of α4β1 integrin.

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Acknowledgments

We would like to acknowledge the contribution of the following members of the Spanish Society of Hematology and Hemotherapy (Erythropathology Group) and the Spanish Society of Pediatric Hematology and Oncology: Adela María Periago, Rafael Ramos, David Beneítez, Jorge Groiss, Isabel Badell, Carlos Scida, Carolina López-Santamaría, Emilia Pardal, Guillermo Martín, Marta Morado, Nieves Alonso, Manuel García, and Roberto Bajo. In addition, we acknowledge the technical and human support provided by the Service of Bioscience-Applied Techniques at SAIUEx (financed by University of Extremadura, Junta de Extremadura, MICINN, FEDER, and FSE). We also thank the patients and controls that participated in this study. This work has been supported in part by grant PI15/00804 from Instituto de Salud Carlos III, Ministry of Health, Madrid, Spain, and by grant GR15012 from “Junta de Extremadura, Consejería de Economia, Comercio e Innovacion,” Mérida, Spain.

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Authors and Affiliations

  1. Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain

    Jose Manuel Vagace, Antonio Corbacho, Teresa Vázquez & Maria Dolores de la Maya

  2. Service of Hematology, Mérida Hospital, Badajoz, Spain

    Rocío Cardesa

  3. Service of Hematology, Hospital Clínico San Carlos, Madrid, Spain

    Fernando Ataulfo Gonzalez

  4. Service of Hematology, Hospital Morales Meseguer, Murcia, Spain

    José Bartolomé Nieto

  5. Service of Pediatric Hematology, Hospital Virgen de las Nieves, Granada, Spain

    Emilia Urrutia

  6. Service of Hematology, Móstoles Hospital, Madrid, Spain

    María Jesus Gómez

  7. Service of Hematology, Alcalá de Henares Hospital, Madrid, Spain

    Teresa Pascual

  8. Service of Hematology, Hospital Universitario Juan XXIII, Tarragona, Spain

    Maria Reyes Aguinaco

  9. Department of Surgical and Medical Therapeutics, School of Medicine, University of Extremadura, Av. Elvas s/n 06071, Badajoz, Spain

    Guillermo Gervasini

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  1. Jose Manuel Vagace
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  2. Rocío Cardesa
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  4. Teresa Vázquez
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  12. Guillermo Gervasini
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Correspondence to Guillermo Gervasini.

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Vagace, J.M., Cardesa, R., Corbacho, A. et al. Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia. Ann Hematol 95, 1419–1427 (2016). https://doi.org/10.1007/s00277-016-2733-8

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  • DOI: https://doi.org/10.1007/s00277-016-2733-8

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