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Comments on: alloimmunization screening after transfusion of red blood cells in a prospective study

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Comments on: alloimmunization screening after transfusion of red blood cells in a prospective study

Laércio de Melo

External Quality Control Program in Immunohematology, Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular - ABHH

Corresponding author Corresponding author: Laércio de Melo Programa Externo de Controle de Qualidade em Imuno-hematologia Rua dos Otoni, 296 - sl / 202-204, Santa Efigênia 30150-270 Belo Horizonte, MG, Brazil laercio@imunohematologia.com.br

A red blood cell (RBC) transfusion is a large-scale intravenous introduction of foreign tissue; this procedure provides a valuable opportunity to study human immunologic response to foreign antigens. Patients receiving RBC transfusions are at risk of forming alloantibodies against donor RBC antigens. The risk of alloimmunization is clinically important, but little is known about the factors governing this risk. In a novel mathematical model for RBC alloimmunization (Stochastic model, a random process) that excluded patients with sickle cell disease (SCD), it was calculated that approximately 13% of the transfusion recipient population are responders and at risk of forming RBC alloantibodies (the risk of forming alloantibodies is not the same as the incidence of alloantibodies)(1,2). The incidence of anti-RBC antibodies is not insignificant and varies widely according to the disease of the patient, history of transfusion, pregnancy and the antigen frequencies of patients versus donors in a geographic location. It is estimated at 1-2 percent in the general hospital population, 5 percent or more in multi-transfused patients and multiparous women and 20 percent or more in patients with transfusion-dependent diseases (e.g. sickle cell anemia, thalassemia, etc.)(3).

Clinically, RBC alloimmunization can result in delays in patient care, hemolytic transfusion reactions, hemolytic disease of the fetus and newborn and possibly increased morbidity following organ transplantation(4,5). Anti-RBC antibody titers frequently drop below detectable levels, allowing units to be transfused with incompatible RBCs resulting in the restimulation of memory cells and an increase in antibody titers.

With longer life expectancy and technological developments, the number of chronic degenerative diseases and more complex chirurgical procedures are increasing along with requests for more blood transfusions which consequently increase the probability of repeat transfusions. Many antibodies may not be detected at the time of a new transfusion event and so the transfusion recipient will be at risk for delayed hemolytic transfusion reactions.

Given the clinical consequences, several retrospective studies have attempted to elucidate clinical and patient variables to help identify patients at increased risk for RBC alloimmunization.

As the majority of studies report on the rate of alloimmunization in chronically transfused patients(6), Santos at al., in a retrospective study published in the Revista Brasileira de Hematologia e Hemoterapia (RBHH), demonstrated the importance of considering the incidence of clinically relevant antibodies in patients transfused in emergency situations(7). This issue of the RBHH includes an original and prospective analysis of patients in surgical and clinical emergency services - Alloimmunization screening after transfusion of red blood cells in a prospective study(8).

The results demonstrated a high rate of alloimmunization within six months of the procedure (15/143 - 10.49%) in patients transfused with packed red blood cells; the titers of these antibodies decreased and disappeared within 15 months of transfusion in 60% of the alloimmunized individuals. Anti-K alloantibodies and those directed against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K) and there was an evident correlation with the number of transfusions. Due to the high incidence of RBC alloantibodies of clinical importance in patients transfused in surgical and clinical emergency services, the authors proposed to extend phenotyping of C, c, E, e and K antigens to all patients with planned surgeries or with acute clinical events that do not need emergency transfusions.

This theme is controversial because preventing the formation of RBC antibodies is not practical for most patients and for many cases alloimmunization is not a serious problem. In addition, blood banking services face challenges with increased financial pressures amidst a growing demand. These financial pressures oblige modern blood banks to focus on improving efficiency. Thus, it is important to emphasize that donor phenotyping, when it is routinely performed using automated micro-assay techniques, often leads to a reduction in costs and a higher quality procedure. In the future the use of automated templates for large-scale phenotyping/genotyping will substantially increase transfusion safety(9). The author's proposal was realistic and will allow the prevention of RBC alloimmunization to be expanded one step further as phenotyping is already essential in women of child bearing age, for some patients at risk of serious hemolytic transfusion reactions and for patients with chronic transfusion requirements, e.g. patients with sickle cell anemia.

References

1. Higgins JM, Sloan SR. Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders. Blood. 2008;112(6)2546-53. Comment in: Blood. 2010;115(21):4315; author reply 4315-6; Blood. 2008;112(6):2180-1.

2. Cooling L. Mining the possibilities behind RBC alloimmunization. Blood. 2008;112(6):2180-1. Comment on: Blood. 2008;112(6):2546-53.

3. Types of transfusion complications [Internet]. Canadian Blood Service; c2009 [cited 2012 May 3]. Available from: http://www.transfusionmedicine.ca/resources/books/vein-vein/complicationsblood-transfusion/types-transfusion-complications

4. Lerut E, Van Damme B, Noizat-Pirenne F, Emonds MP, Rouger P, Vanrenterghem Y, et al. Duffy and Kidd blood group antigens: minor histocompatibility antigens involved in renal rejection? Transfusion. 2007;47(1):28-40.

5. Boyd SD, Stenard F, Lee DK, Goodnough LT, Esquivel CO, Fontaine MJ. Alloimmunization to red blood cell antigens affects clinical outcomes in liver transplant patients. Liver Transpl. 2007;13(12):1654-61. Comment in: Liver Transpl. 2007;13(12):1630-2.

6. Schonewille H, van de Watering LM, Brand A. Additional red blood cell alloantibodies after blood transfusions in a non-hematologic alloimmunized patient cohort: is it time to take precautionary measures? Transfusion. 2006;46(4):630-5.

7. Santos FW, Magalhães SM, Mota RM, Pitombeira MH. Posttransfusion red alloimmunization in patients with acute disorders and medical emergencies. Rev Bras Hematol Hemoter. 2007;29(4):369-72.

8. Alves VM, Martins PR, Soares S, Araújo G, Schmidt LC, Costa SS, Langhi Júnior DM, Moraes-Souza H. Alloimmunization screening after transfusion of red blood cells in a prospective study. Rev Bras Hematol Hemoter. 2012;34(3)206-11.

9. Castilho L. [The future of red cell alloimmunization]. Rev Bras Hematol Hemoter. 2008;30(4):261-2. Portuguese.

Submitted: 5/11/2012

Accepted: 5/12/2012

Conflict-of-interest disclosure: The authors declare no competing financial interest

www.rbhh.org or www.scielo.br/rbhh

  • 1. Higgins JM, Sloan SR. Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders. Blood. 2008;112(6)2546-53.
  • Comment in: Blood. 2010;115(21):4315; author reply 4315-6;
  • Blood. 2008;112(6):2180-1.
  • 2. Cooling L. Mining the possibilities behind RBC alloimmunization. Blood. 2008;112(6):2180-1.
  • Comment on: Blood. 2008;112(6):2546-53.
  • 3. Types of transfusion complications [Internet]. Canadian Blood Service; c2009 [cited 2012 May 3]. Available from: http://www.transfusionmedicine.ca/resources/books/vein-vein/complicationsblood-transfusion/types-transfusion-complications
  • 4. Lerut E, Van Damme B, Noizat-Pirenne F, Emonds MP, Rouger P, Vanrenterghem Y, et al. Duffy and Kidd blood group antigens: minor histocompatibility antigens involved in renal rejection? Transfusion. 2007;47(1):28-40.
  • 5. Boyd SD, Stenard F, Lee DK, Goodnough LT, Esquivel CO, Fontaine MJ. Alloimmunization to red blood cell antigens affects clinical outcomes in liver transplant patients. Liver Transpl. 2007;13(12):1654-61.
  • Comment in: Liver Transpl. 2007;13(12):1630-2.
  • 6. Schonewille H, van de Watering LM, Brand A. Additional red blood cell alloantibodies after blood transfusions in a non-hematologic alloimmunized patient cohort: is it time to take precautionary measures? Transfusion. 2006;46(4):630-5.
  • 7. Santos FW, Magalhães SM, Mota RM, Pitombeira MH. Posttransfusion red alloimmunization in patients with acute disorders and medical emergencies. Rev Bras Hematol Hemoter. 2007;29(4):369-72.
  • 8. Alves VM, Martins PR, Soares S, Araújo G, Schmidt LC, Costa SS, Langhi Júnior DM, Moraes-Souza H. Alloimmunization screening after transfusion of red blood cells in a prospective study. Rev Bras Hematol Hemoter. 2012;34(3)206-11.
  • 9. Castilho L. [The future of red cell alloimmunization]. Rev Bras Hematol Hemoter. 2008;30(4):261-2. Portuguese.
  • Corresponding author:

    Laércio de Melo
    Programa Externo de Controle de Qualidade em Imuno-hematologia
    Rua dos Otoni, 296 - sl / 202-204, Santa Efigênia
    30150-270 Belo Horizonte, MG, Brazil
  • Publication Dates

    • Publication in this collection
      08 Aug 2012
    • Date of issue
      2012
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