Original article
Red-cell alloimmunization profile in multi transfused patients: Findings and insights of a blood transfusion serviceProfil d’allo-immunisation érythrocytaire chez les patients multi-transfusés : résultats et perceptions d’un service de transfusion sanguine

https://doi.org/10.1016/j.tracli.2021.04.006Get rights and content

Abstract

Objectives

Blood transfusion is a key intervention for decreasing morbidity and mortality in many cases and, besides its importance, potentially fatal consequences of incompatible transfusion are a great risk to patients. This study evaluated the incidence and specificity of erythrocyte alloantibodies in multi-transfused patients enrolled at an important Regional Blood Center.

Materials/methods

This was a single-center retrospective cohort study that eveluated patients enrolled at a Regional Blood Center in a period of four years. A total of 29,128 patient samples were screened, out of which 79 (0.27%) were multiple-transfused patients with alloantibodies identified.

Results

The most common alloantibody found was anti-E (22.55%) followed by anti-D (14.71%), anti-C (5.88%), anti-c (5.88%), anti-e (1.96%) and anti-Cw (0.98%). We also identified combinations of alloantibodies (25.32%), 5.88% of which showed an IgG autoantibody isolated or combined with alloantibodies. The most frequent reason for the need of blood transfusion included cases of surgery, emergency and urgency (36.71%).

Conclusions

A low rate of development of alloantibodies in multi-transfused patients was found, which could be a consequence of the implementation of red blood cell phenotyping for patients who may receive frequent transfusions, as in the case of some hematological neoplasms and hemoglobinopathies. However, the most common alloantibodies identified were against the Rh and/or Kell systems, with high clinical significance since both can cause delayed hemolytic transfusion reactions. Thus, the implementation of reliable antibody screening tests and the transfusion of phenotyped units for selected patients in all transfusion services represent important measures to increase transfusion safety.

Résumé

Objectifs

La transfusion sanguine est une intervention fondamentale pour diminuer la morbidité et la mortalité dans de nombreux cas et, en plus de son importance, les conséquences potentiellement mortelles d’une transfusion incompatible sont un grand risque pour les patients. Cette étude a évalué l’incidence et la spécificité des alloanticorps érythrocytaires chez des patients polythérocytaires inscrits dans un important centre sanguin régional.

Méthodes

Il s’agissait d’une étude de cohorte rétrospective monocentrique qui évaluait les patients inscrits dans un centre régional de transfusion sanguine sur une période de quatre ans. Un total de 29 128 échantillons de patients ont été examinés, dont 79 (0,27 %) étaient des patients transfusés avec des alloanticorps identifiés.

Résultats

L’alloanticorps le plus couramment trouvé était l’anti-E (22,55 %) suivi par l’anti-D (14,71 %), l’anti-C (5,88 %), l’anti-c (5,88 %), l’anti-e (1,96 %) et anti-Cw (0,98 %). Nous avons également identifié des combinaisons d’alloanticorps (25,32 %), dont 5,88 % avaient un auto-anticorps IgG seul ou combiné avec des alloanticorps. La raison la plus fréquente de la nécessité d’une transfusion sanguine comprenait les cas de chirurgie, d’urgence et d’urgence (36,71 %).

Conclusions

Un faible taux de développement d’alloanticorps a été trouvé chez les patients multitransfusionnés, ce qui peut être une conséquence de la mise en œuvre du phénotypage des globules rouges chez les patients susceptibles de recevoir des transfusions fréquentes, comme c’est le cas de certaines néoplasmes hématologiques et hémoglobinopathies. Cependant, les alloanticorps les plus couramment identifiés étaient contre les systèmes Rh et/ou Kell, avec une signification clinique élevée, car les deux peuvent provoquer des réactions transfusionnelles hémolytiques tardives. Ainsi, la mise en œuvre de tests de dépistage d’anticorps fiables et la transfusion d’unités phénotypées pour des patients sélectionnés dans tous les services de transfusion représentent des mesures importantes pour augmenter la sécurité transfusionnelle.

Introduction

Blood transfusions are often necessary after injury or surgery, in order to acutely restore hemodynamics. Transfusion therapy is also a key intervention to decreasing morbidity and mortality, mainly in patients with neoplasia, kidney diseases and hematological diseases (such as sickle cell disease, leukemia and hemophilia). Although this process brings benefits, serious outcomes can occur if patient's and donor's blood have genetic disparities and are not compatible, as red blood cell (RBC) alloimmunization and delayed hemolytic transfusion reactions or, in cases of high demand of blood transfusion, increased risk of iron overload [1]. Nowadays, transfusion services have more advanced techniques and higher acceptance of better procedures to prevent such outcomes, as pre-transfusion testing that can detect autoantibodies and alloantibodies [2].

The development of alloimmunization, an immune response after exposure to foreign antigens from genetically different cells, results in the production of irregular antibodies. The presence of alloantibodies is clinically significant in future transfusions since it can result in hemolytic transfusion reactions (acute or delayed) and can hamper the provision of compatible blood units [3]. Multi-transfused patients have a higher risk of producing alloantibodies due to the exposure of the immune system to a multitude of foreign antigens that induces a prompt immune response, mostly after the second exposition, which results in various clinical consequences, depending on the blood cells and specific antigens involved [4]. Some alloantibodies are immunogenic and can cause severe transfusion reactions, as those associated to the ABO and Rhesus (Rh) red blood cell systems. The ABO blood group is characterised by the expression of two carbohydrate antigens, called A and B, that are expressed on the red blood cell membrane and other tissues by two naturally occurring antibodies found in the serum, which appear after birth, called anti-A and anti-B. The Rh system is the most polymorphic of the human blood groups, consisting of at least 45 independent antigens. The most common Rh antigens are D, C, c, E and e [5].

Considering the importance of the blood group antigens and the potentially fatal consequences of incompatible transfusion, this study was performed to evaluate the incidence and specificity of erythrocyte alloantibodies in multi-transfused patients enrolled at an important regional blood center in the state of São Paulo, southeastern Brazil, over a period of four years. We also aimed at identifying the variables affecting the extent of alloimmunization in repeated transfusions patients. Correlating alloantibody specificities and the possible factors related to alloimmunization development can be helpful to prevent its occurrence and, consequently, the impacts of delayed hemolytic transfusion reactions as well as delays and difficulties in identifying appropriate blood units.

Section snippets

Study design

This was a single-center retrospective non-randomized cohort study performed at Regional Blood Center of Bragança Paulista (São Paulo, Brazil), evaluating data from 29,128 transfused patients (transfusion protocols according World Health Organization) that were registered in the service from January 2014 to December 2017. Seventy-nine multi-transfused patients that had detectable red blood cells autoantibodies and/or alloantibodies were included in the study. Multi-transfused patients were

Transfused patient characteristics

During the study period, 29,128 samples were typed and screened, from patients assisted by inpatient and outpatient care. There was a prevalence of 320 (1.10%) positive antibody-screening tests from patients that received at least one transfusion unit, out of which 79 were multi-transfused patients (0.27%) (Table 1).

Factors including sex, age and total number of units transfused were analysed in order to search for any significant risk factors associated with alloimmunization development. Males

Discussion

The main reasons for blood transfusion in clinical practice are restoring oxygen delivery to hypoxic tissue and organs and, concomitantly, protecting patients against significant bleeding. Due to its great importance, blood transfusion practice have been improved and are currently considered safe [7]; however, there are risks ranging from mild (itching, fever, hives, rash, and allergy) to potentially life threatening (pathogen infection, severe hemolysis, and graft-versus-host disease) [8].

Conclusions

A relatively low rate of alloantibodies in multi-transfused patients enrolled at the regional blood center of Bragança Paulista over a period of 4 years, from January 2014 to December 2017, could be a consequence of the implementation of the red blood cell phenotype for patients who may receive therapeutic multi-transfusions. The implementation of such routine in all transfusion medicine services could be an important contribution to increase transfusion safety. Moreover, regular antibody

Funding

This work was supported by the Universidade São Francisco [Programa de Iniciação Científica, Iniciação Tecnológica e Extensão (PICITExt) da Universidade São Francisco – USF (Edital Proepe 2/2016 and 2/2017)].

Author contribution

M.L.P.B. was the principal investigator of this study, collecting, analysing and interpreting data, and writing the manuscript; M.B.M. collected and analysed data; JARS collected patients samples, registered patient's data and performed all experimental assays; B.D.B. acted as reference physician and revised the manuscript; F.M.R. provided the study conception, directed the research, helped analysing and interpreting data, revised and gave final approval of the manuscript.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgments

The authors would like to thank Regional Blood Center of Bragança Paulista, Hospital Universitário São Francisco (HUSF) and Centro de Diagnóstico Laboratorial São José for their medical and laboratorial assistance. We also thank Universidade São Franscisco for academic assistance.

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