LETTER TO THE EDITOR Blood group genotyping for patients with autoimmune hemolytic anemia
W
e read with great interest the paper of El Kenz et al.1 The authors emphasize the importance of red blood cell (RBC) genotyping for patients with autoimmune hemolytic anemia (AIHA). AIHA is characterized by different types of autoantibodies directed against RBCs that reduce the survival of erythrocytes and cause hemolytic reactions. These antibodies can be divided into warm, mixed, or cold reactive subtypes resulting from optimal autoantibody reactivity temperatures.2 AIHA may be primary or secondary to infection, associated with neoplastic and autoimmune disorders. The diagnosis is based on clinical signs and laboratory tests or the identification of autoantibodies through the direct antiglobulin test, which that is 1 of the most important pieces of evidence of AIHA.3 Several studies4,5 have demonstrated the spectrum of treatment for patients with AIHA, including corticosteroids, splenectomy, immunosuppressive agents, and monoclonal antibodies, in particular for hemolytic anemia with warm autoantibodies. Blood transfusions are necessary in some patients as a result of an inadequate response to therapy. However, transfusions may be complicated by the presence of autoantibodies, leading to the destruction of donor RBCs. We agree with the authors that the introduction of RBC antigen genotyping (including RH1, RH2, RH3, RH4, RH5, KEL1, FY1, FY2, JK1, JK2, MNS1, MNS2, MNS3, and MNS4) has provided considerable support to serology for the assignment of blood components.6 Indeed, it has been reported that for patients
Reprint requests: Angela Belsito, U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology (SIMT), Regional Reference Laboratory of Transplant Immunology (LIT), Azienda Universitaria Policlinico (AOU), Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy; e-mail: [email protected]. Conflicts of Interest: The authors have read the journals policy on disclosing potential conflicts of interest and have none to declare. Submitted for publication March 11, 2014; accepted for publication March 14, 2014. Translational Research 2014;-:1–2. 1931-5244/$ - see front matter Ó 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.trsl.2014.03.009
with AIHA, as well as for those with sickle cell disease or thalassemia, pretransfusion conventional tests are considered difficult because of the presence of autoand alloantibodies.7 The rate of alloimmunization in patients with AIHA is still greater than in those with sickle cell disease or thalassemia (both of which are supported regularly by our division). The patients in the study by El Kenz et al1 experienced the benefits of this transfusion strategy, showing a satisfactory recovery posttransfusion without any reaction. Furthermore, the adsorption procedure performed 1 week after transfusion did not reveal the presence of any alloantibodies. More relevant, the molecular method has the advantage of typing by starting with a small volume of blood for pediatric patients. In our patients with sickle cell disease and thalassemia, our preliminary data confirm a very good correlation (97.7%) between serologic and molecular results. In particular, molecular analysis was more reliable for polytransfused patients for Rhesus (Rh) CE alleles. Our current practice is to perform compatibility for AB0, Rh, and Kell antigens only, whereas the RBC molecular assay can be extended to other antigenic blood group systems, ensuring a ‘‘perfect match,’’ better quality, and effectiveness of transfusion therapy. Indeed, a more extensive antigenic match decreases the risk of hemolytic transfusion reactions—in particular, those resulting from antibodies already present—and prevents new cases of alloimmunization.8 Furthermore, RBC genotyping is important in subjects with a different phenotype from that of donors. The lack of complete compatibility of RBC antigens between donors and recipients (mainly among white and black patients) is one of the most significant factors of alloimmunization.9 An important association has been noted between some specific human leukocyte antigen alleles such as DRB1*04 and DRB1*15, and phenotype Fy(a–b1), because the majority of these patients develop a hemolytic transfusion reaction resulting from the production of the antibody anti-Fya.10 This could be a starting point for a future study of the association between human leukocyte antigen typing and erythrocyte antigens. It is clear the clinical benefits observed by RBC genotyping are more interesting in transfusion-dependent patients.11 A ‘‘perfect match’’ resulted by RBC 1
2
Belsito et al
genotyping, allows us to extend the time between a transfusion and the other. Angela Belsitoa,* Dario Costaa Claudio Napolia,b a U.O.C. Immunohematology Transfusion Medicine and Transplant Immunology (SIMT) Regional Reference Laboratory of Transplant Immunology (LIT), Azienda Universitaria Policlinico (AOU) Second University of Naples Naples, Italy b Department of Biochemistry Biophysics and General Pathology Second University of Naples Naples, Italy
REFERENCES
1. El Kenz H, Efira A, Le PQ, et al. Transfusion support of autoimmune hemolytic anemia: how could the blood group genotyping help? Transl Res 2014;163:36–42. 2. Bass GF, Tuscano ET, Tuscano JM. Diagnosis and classification of autoimmune hemolytic anemia. Autoimmun Rev 2014;13: 560–4.
Translational Research - 2014
3. Zantek ND, Koepsell SA, Tharp DR Jr., Cohn CS. The direct antiglobulin test: a critical step in the evaluation of hemolysis. Am J Hematol 2012;87:707–9. 4. Michel M. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update. Expert Rev Hematol 2011;4: 607–18. 5. Lechner K, J€ager U. How I treat autoimmune hemolytic anemias in adults. Blood 2010;116:1831–8. 6. Reid ME, Denomme GA. DNA-based methods in the immunohematology reference laboratory. Transfus Apher Sci 2011;44: 65–72. 7. Segel GB, Lichtman MA. Direct antiglobulin (‘‘Coombs’’) testnegative autoimmune hemolytic anemia: a review. Blood Cells Mol Dis 2014;52:152–60. 8. Klapper E, Zhang Y, Figueroa P, et al. Toward extended phenotype matching: a new operational paradigm for the transfusion service. Transfusion 2010;50:536–46. 9. Badjie KS, Tauscher CD, van Buskirk CM, et al. Red blood cell phenotype matching for various ethnic groups. Immunohematology 2011;27:12–9. 10. Picard C, Frassati C, Basire A, et al. Positive association of DRB1 04 and DRB1 15 alleles with Fya immunization in a southern European population. Transfusion 2009;49:2412–7. 11. O’Suoji C, Liem RI, Mack AK, Kingsberry P, Ramsey G, Thompson AA. Alloimmunization in sickle cell anemia in the era of extended red cell typing. Pediatr Blood Cancer 2013;60: 1487–91.
W
e read with great interest the paper of El Kenz et al.1 The authors emphasize the importance of red blood cell (RBC) genotyping for patients with autoimmune hemolytic anemia (AIHA). AIHA is characterized by different types of autoantibodies directed against RBCs that reduce the survival of erythrocytes and cause hemolytic reactions. These antibodies can be divided into warm, mixed, or cold reactive subtypes resulting from optimal autoantibody reactivity temperatures.2 AIHA may be primary or secondary to infection, associated with neoplastic and autoimmune disorders. The diagnosis is based on clinical signs and laboratory tests or the identification of autoantibodies through the direct antiglobulin test, which that is 1 of the most important pieces of evidence of AIHA.3 Several studies4,5 have demonstrated the spectrum of treatment for patients with AIHA, including corticosteroids, splenectomy, immunosuppressive agents, and monoclonal antibodies, in particular for hemolytic anemia with warm autoantibodies. Blood transfusions are necessary in some patients as a result of an inadequate response to therapy. However, transfusions may be complicated by the presence of autoantibodies, leading to the destruction of donor RBCs. We agree with the authors that the introduction of RBC antigen genotyping (including RH1, RH2, RH3, RH4, RH5, KEL1, FY1, FY2, JK1, JK2, MNS1, MNS2, MNS3, and MNS4) has provided considerable support to serology for the assignment of blood components.6 Indeed, it has been reported that for patients
Reprint requests: Angela Belsito, U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology (SIMT), Regional Reference Laboratory of Transplant Immunology (LIT), Azienda Universitaria Policlinico (AOU), Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy; e-mail: [email protected]. Conflicts of Interest: The authors have read the journals policy on disclosing potential conflicts of interest and have none to declare. Submitted for publication March 11, 2014; accepted for publication March 14, 2014. Translational Research 2014;-:1–2. 1931-5244/$ - see front matter Ó 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.trsl.2014.03.009
with AIHA, as well as for those with sickle cell disease or thalassemia, pretransfusion conventional tests are considered difficult because of the presence of autoand alloantibodies.7 The rate of alloimmunization in patients with AIHA is still greater than in those with sickle cell disease or thalassemia (both of which are supported regularly by our division). The patients in the study by El Kenz et al1 experienced the benefits of this transfusion strategy, showing a satisfactory recovery posttransfusion without any reaction. Furthermore, the adsorption procedure performed 1 week after transfusion did not reveal the presence of any alloantibodies. More relevant, the molecular method has the advantage of typing by starting with a small volume of blood for pediatric patients. In our patients with sickle cell disease and thalassemia, our preliminary data confirm a very good correlation (97.7%) between serologic and molecular results. In particular, molecular analysis was more reliable for polytransfused patients for Rhesus (Rh) CE alleles. Our current practice is to perform compatibility for AB0, Rh, and Kell antigens only, whereas the RBC molecular assay can be extended to other antigenic blood group systems, ensuring a ‘‘perfect match,’’ better quality, and effectiveness of transfusion therapy. Indeed, a more extensive antigenic match decreases the risk of hemolytic transfusion reactions—in particular, those resulting from antibodies already present—and prevents new cases of alloimmunization.8 Furthermore, RBC genotyping is important in subjects with a different phenotype from that of donors. The lack of complete compatibility of RBC antigens between donors and recipients (mainly among white and black patients) is one of the most significant factors of alloimmunization.9 An important association has been noted between some specific human leukocyte antigen alleles such as DRB1*04 and DRB1*15, and phenotype Fy(a–b1), because the majority of these patients develop a hemolytic transfusion reaction resulting from the production of the antibody anti-Fya.10 This could be a starting point for a future study of the association between human leukocyte antigen typing and erythrocyte antigens. It is clear the clinical benefits observed by RBC genotyping are more interesting in transfusion-dependent patients.11 A ‘‘perfect match’’ resulted by RBC 1
2
Belsito et al
genotyping, allows us to extend the time between a transfusion and the other. Angela Belsitoa,* Dario Costaa Claudio Napolia,b a U.O.C. Immunohematology Transfusion Medicine and Transplant Immunology (SIMT) Regional Reference Laboratory of Transplant Immunology (LIT), Azienda Universitaria Policlinico (AOU) Second University of Naples Naples, Italy b Department of Biochemistry Biophysics and General Pathology Second University of Naples Naples, Italy
REFERENCES
1. El Kenz H, Efira A, Le PQ, et al. Transfusion support of autoimmune hemolytic anemia: how could the blood group genotyping help? Transl Res 2014;163:36–42. 2. Bass GF, Tuscano ET, Tuscano JM. Diagnosis and classification of autoimmune hemolytic anemia. Autoimmun Rev 2014;13: 560–4.
Translational Research - 2014
3. Zantek ND, Koepsell SA, Tharp DR Jr., Cohn CS. The direct antiglobulin test: a critical step in the evaluation of hemolysis. Am J Hematol 2012;87:707–9. 4. Michel M. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update. Expert Rev Hematol 2011;4: 607–18. 5. Lechner K, J€ager U. How I treat autoimmune hemolytic anemias in adults. Blood 2010;116:1831–8. 6. Reid ME, Denomme GA. DNA-based methods in the immunohematology reference laboratory. Transfus Apher Sci 2011;44: 65–72. 7. Segel GB, Lichtman MA. Direct antiglobulin (‘‘Coombs’’) testnegative autoimmune hemolytic anemia: a review. Blood Cells Mol Dis 2014;52:152–60. 8. Klapper E, Zhang Y, Figueroa P, et al. Toward extended phenotype matching: a new operational paradigm for the transfusion service. Transfusion 2010;50:536–46. 9. Badjie KS, Tauscher CD, van Buskirk CM, et al. Red blood cell phenotype matching for various ethnic groups. Immunohematology 2011;27:12–9. 10. Picard C, Frassati C, Basire A, et al. Positive association of DRB1 04 and DRB1 15 alleles with Fya immunization in a southern European population. Transfusion 2009;49:2412–7. 11. O’Suoji C, Liem RI, Mack AK, Kingsberry P, Ramsey G, Thompson AA. Alloimmunization in sickle cell anemia in the era of extended red cell typing. Pediatr Blood Cancer 2013;60: 1487–91.
![[Blood transfusion in autoimmune hemolytic anemia].](/assets/img/hold.png)
