title: Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia.
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.
authors.affiliation: Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Vagace
authors.affiliation: Service of Hematology, Mérida Hospital, Badajoz, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Cardesa
authors.affiliation: Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Corbacho
authors.affiliation: Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Vázquez
authors.affiliation: Service of Hematology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: de la Maya
authors.affiliation: Service of Hematology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Fernando Ataulfo
authors.initials: FA
authors.lastname: Gonzalez
authors.affiliation: Service of Hematology, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: José Bartolomé
authors.initials: JB
authors.lastname: Nieto
authors.affiliation: Service of Pediatric Hematology, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: Emilia
authors.initials: E
authors.lastname: Urrutia
authors.affiliation: Service of Hematology, Móstoles Hospital, Madrid, Spain.
authors.forename: María Jesus
authors.initials: MJ
authors.lastname: Gómez
authors.affiliation: Service of Hematology, Alcalá de Henares Hospital, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pascual
authors.affiliation: Service of Hematology, Hospital Universitario Juan XXIII, Tarragona, Spain.
authors.forename: Maria Reyes
authors.initials: MR
authors.lastname: Aguinaco
authors.affiliation: Department of Surgical and Medical Therapeutics, School of Medicine, University of Extremadura, Av. Elvas s/n 06071, Badajoz, Spain. ggervasi@unex.es.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gervasini
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001803:Blood Transfusion / Q000379:methods*; D018955:CD36 Antigens / Q000097:blood; D018957:CD59 Antigens / Q000097:blood; D015926:Complement C3a / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D039423:Integrin alpha1 / Q000097:blood; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D012156:Reticulocytes / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain; D013577:Syndrome; D013789:Thalassemia / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D055538:delta-Thalassemia / Q000097:blood / Q000503:physiopathology / Q000628:therapy
chemical_list: D018955:CD36 Antigens; D018957:CD59 Antigens; D039423:Integrin alpha1; C051590:CD59 protein, human; D015926:Complement C3a
keywords: Adhesion molecules; Delayed hemolytic transfusion reaction; Hyperhemolysis syndrome; Spain; Thalassemia