- Email: [email protected]
Red cell alloimmunization in thalassemia patients in a developing country – What can be done?
Transfusion and Apheresis Science 50 (2014) 310–311
Contents lists available at ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Letter to the editor Red cell alloimmunization in thalassemia patients in a developing country – What can be done?
Dear Editor, b-Thalassemia major is the major hemoglobinopathy in Pakistan. It has been recognized as a significant health problem with an incidence of over 5% in our general population [1]. This disorder is characterized by reduced synthesis of b-globin chains of hemoglobin with subsequent anemia of variable severity, considerable morbidity affecting various organs of the body and has a high mortality. Currently, successful hematopoietic stem cell transplantation from an HLA matched sibling is the only curative option [2] which however owing to the high cost may not be a viable alternative for the majority of thalassemia patients in Pakistan. Therefore, regular life long blood transfusions along with adequate iron chelation remain the mainstay of treatment [3]. Repeated blood transfusions may be associated with transmission of blood borne pathogens, iron overload (siderosis) and red cell immunization [2]. Red cell alloimmunization is the development of alloantibodies in recipients of allogenic red cell transfusions. Since the blood is typically matched for A, B and D antigens before transfusion, disparity of other red cell antigens like rhesus (E, e, C, c), Kell (K, k), Duffy (Fya, Fyb) and Kidd (Jka, Jkb) can result in hemolytic transfusion reactions in recipients with corresponding alloantibodies. The immunity against red cell antigens is not unique to thalassemics but is reportedly seen in other conditions as well requiring chronic red cell transfusions. Important among these are sickle cell disease, solid malignancies and hematopoietic stem cell transplants [4]. Red cell alloimmunization has been observed in Pakistani thalassemia patients by Bhatti et al. in 2004 [5] and Bilwani et al. in 2005 [6]. The reported frequency respectively was 6.8% and 9%. The first study was observed in Karachi evaluating 97 patients and red cell antibodies identified were rhesus (anti-D, Anti-C, and anti-E) and anti K. The later report was from Rawalpindi assessing 161 thalassemics and identified Rh antibodies, anti-K, anti-Jsb and anti-Jka. In a similar setting, Hassan et al. [7] reported a relatively higher rate of 22%. The important red cell 1473-0502/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.transci.2014.01.007
antibodies identified in these patients were rhesus (Anti- E) and Anti-K. Age at the time of transfusion, splenectomy and disparity between recipient and donor red cell antigens have been identified as the important determinants of red cell alloimmunization in thalassemics. Autoimmunity to red cells is a significant though often unrecognized dilemma associated with red cell alloimmunization. This will not only result in hemolysis of patient’s own red cells but will also lead to considerable difficulty for a technologist in finding a compatible blood unit. Leucodepleted blood products owing to the impact on reducing HLA immunization [8] may be beneficial in reducing the incidence of red cell alloimmunization. However, such a favorable affect has not been observed in any of the Pakistani studies due to the expense involved. Transfusion of extended typed red cells (matched for minor red cell antigens as well) has been utilized as a measure to minimize red cell immunity in these patients [9]. Some observers have criticized the cost of these expensive transfusions vs. the benefit obtained [10]. Effective working guidelines are needed for preventing red cell alloimmunization in our patients considering our financial constrains. Currently, the magnitude of the problem ranges from 5% to 22% in our thalassemia patients. Although no studies addressing the ethnic diversity of red cell antigens are available for Pakistan, lack of dissimilarity between blood donors’ and recipients’ red cell antigens may have resulted in a lower frequency compared to the frequency of red cell transfusion in these patients. The author believes that all thalassemics should be typed for rhesus and Kell antigens before their first transfusion. This will greatly aid in identifying the recipients who are at risk of developing red cell antibodies. Since Anti K and Anti E are mostly implicated in our thalassemics, Kell negative or E negative patients may be considered to receive K-/E- red cells from the very beginning. In house red cell antibody screening can be used at the time of setting cross match prior to red cell transfusion. This will enable the technologist to identify any red cell antibody developed by these recipients and antigen negative blood can be arranged accordingly. Leucodepletion of blood products for prevention of red cell immunization is neither cost effective nor warranted. A simple practical approach would be to increase awareness among the masses and the health care professionals to start early transfusion in
Letter to the editor / Transfusion and Apheresis Science 50 (2014) 310–311
thalassemic babies. A pre-transfusion hemoglobin of 9–10 g/dl could also reduce the chances of immunization compared to a hyper-transfusion regime. All patients who have already developed red cell antibodies must receive antigen negative blood. Yours sincerely, Bushra Moiz Associate Professor, Section of Hematology, The Aga Khan University, Pakistan References [1] Hafeez M, Aslam M, Ali A, Rashid Y, Jafri H. Regional and ethnic distribution of beta thalassemia mutations and effect of consanguinity in patients referred for prenatal diagnosis. J Coll Physicians Surg Pak 2007;17(3):144–7. [2] Old MJ, Olivieri NF, Thein SL. Diagnosis and management of thalassemia. In: Wetherall DJ, Clegg B, editors. The thalassaemia syndromes. Oxform (England): Blackwell Science; 2001. p. 630–85. [3] Rund D, Rachmilewitz E. b-Thlassemia. N Eng J Med 2005;353:1135–46. [4] Campbell-Lee SA. The future of red cell alloimmunization. Transfusion 2007;47:1959–60.
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[5] Bhatti FA, Salamat N, Nadeem A, Shabiir N. Red cell immunization in beta thalassemia major. J Coll Physicians Surg Pak 2004;14(11):657–60. [6] Bilwani F, Kakepoto GN, Adil SN, Usman M, Hassan F, Khurshid M. Frequency of irregular alloantibodies in patients with thalassemia major: a bi-center study. J Pak Med Assoc 2005;55:563–5. [7] Hassan Khalid, Younus Muhammad, Ikram Nadeem, Naseem Lubna, Zaheer Hassan Abbas. Red cell alloimmunization in repeatedly transfused thalassemia major patients. Int J Path 2004;2(1):16–9. [8] Coles SM, Klein HG, Holland PV. Alloimmunization in two multi transfused patient populations. Transfusion 1981;21:462–6. [9] Sirchia G, Rebulla P, Mascaretti L, et al. The clinical importance of leukocyte depletion in regular erythrocyte transfusions. Vox Sang 1986;51(Suppl. 1):2–8. [10] Blumberg N, Ross K, Avila E, Peck K. Should chronic transfusions be matched for antigens other than ABO and Rho(D)? Vox Sang 1984;47(3):205–8.
Bushra Moiz Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi, Pakistan Tel.: +92 21 4864511x1302; fax: +92 213 4934294. E-mail address: [email protected]
Contents lists available at ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Letter to the editor Red cell alloimmunization in thalassemia patients in a developing country – What can be done?
Dear Editor, b-Thalassemia major is the major hemoglobinopathy in Pakistan. It has been recognized as a significant health problem with an incidence of over 5% in our general population [1]. This disorder is characterized by reduced synthesis of b-globin chains of hemoglobin with subsequent anemia of variable severity, considerable morbidity affecting various organs of the body and has a high mortality. Currently, successful hematopoietic stem cell transplantation from an HLA matched sibling is the only curative option [2] which however owing to the high cost may not be a viable alternative for the majority of thalassemia patients in Pakistan. Therefore, regular life long blood transfusions along with adequate iron chelation remain the mainstay of treatment [3]. Repeated blood transfusions may be associated with transmission of blood borne pathogens, iron overload (siderosis) and red cell immunization [2]. Red cell alloimmunization is the development of alloantibodies in recipients of allogenic red cell transfusions. Since the blood is typically matched for A, B and D antigens before transfusion, disparity of other red cell antigens like rhesus (E, e, C, c), Kell (K, k), Duffy (Fya, Fyb) and Kidd (Jka, Jkb) can result in hemolytic transfusion reactions in recipients with corresponding alloantibodies. The immunity against red cell antigens is not unique to thalassemics but is reportedly seen in other conditions as well requiring chronic red cell transfusions. Important among these are sickle cell disease, solid malignancies and hematopoietic stem cell transplants [4]. Red cell alloimmunization has been observed in Pakistani thalassemia patients by Bhatti et al. in 2004 [5] and Bilwani et al. in 2005 [6]. The reported frequency respectively was 6.8% and 9%. The first study was observed in Karachi evaluating 97 patients and red cell antibodies identified were rhesus (anti-D, Anti-C, and anti-E) and anti K. The later report was from Rawalpindi assessing 161 thalassemics and identified Rh antibodies, anti-K, anti-Jsb and anti-Jka. In a similar setting, Hassan et al. [7] reported a relatively higher rate of 22%. The important red cell 1473-0502/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.transci.2014.01.007
antibodies identified in these patients were rhesus (Anti- E) and Anti-K. Age at the time of transfusion, splenectomy and disparity between recipient and donor red cell antigens have been identified as the important determinants of red cell alloimmunization in thalassemics. Autoimmunity to red cells is a significant though often unrecognized dilemma associated with red cell alloimmunization. This will not only result in hemolysis of patient’s own red cells but will also lead to considerable difficulty for a technologist in finding a compatible blood unit. Leucodepleted blood products owing to the impact on reducing HLA immunization [8] may be beneficial in reducing the incidence of red cell alloimmunization. However, such a favorable affect has not been observed in any of the Pakistani studies due to the expense involved. Transfusion of extended typed red cells (matched for minor red cell antigens as well) has been utilized as a measure to minimize red cell immunity in these patients [9]. Some observers have criticized the cost of these expensive transfusions vs. the benefit obtained [10]. Effective working guidelines are needed for preventing red cell alloimmunization in our patients considering our financial constrains. Currently, the magnitude of the problem ranges from 5% to 22% in our thalassemia patients. Although no studies addressing the ethnic diversity of red cell antigens are available for Pakistan, lack of dissimilarity between blood donors’ and recipients’ red cell antigens may have resulted in a lower frequency compared to the frequency of red cell transfusion in these patients. The author believes that all thalassemics should be typed for rhesus and Kell antigens before their first transfusion. This will greatly aid in identifying the recipients who are at risk of developing red cell antibodies. Since Anti K and Anti E are mostly implicated in our thalassemics, Kell negative or E negative patients may be considered to receive K-/E- red cells from the very beginning. In house red cell antibody screening can be used at the time of setting cross match prior to red cell transfusion. This will enable the technologist to identify any red cell antibody developed by these recipients and antigen negative blood can be arranged accordingly. Leucodepletion of blood products for prevention of red cell immunization is neither cost effective nor warranted. A simple practical approach would be to increase awareness among the masses and the health care professionals to start early transfusion in
Letter to the editor / Transfusion and Apheresis Science 50 (2014) 310–311
thalassemic babies. A pre-transfusion hemoglobin of 9–10 g/dl could also reduce the chances of immunization compared to a hyper-transfusion regime. All patients who have already developed red cell antibodies must receive antigen negative blood. Yours sincerely, Bushra Moiz Associate Professor, Section of Hematology, The Aga Khan University, Pakistan References [1] Hafeez M, Aslam M, Ali A, Rashid Y, Jafri H. Regional and ethnic distribution of beta thalassemia mutations and effect of consanguinity in patients referred for prenatal diagnosis. J Coll Physicians Surg Pak 2007;17(3):144–7. [2] Old MJ, Olivieri NF, Thein SL. Diagnosis and management of thalassemia. In: Wetherall DJ, Clegg B, editors. The thalassaemia syndromes. Oxform (England): Blackwell Science; 2001. p. 630–85. [3] Rund D, Rachmilewitz E. b-Thlassemia. N Eng J Med 2005;353:1135–46. [4] Campbell-Lee SA. The future of red cell alloimmunization. Transfusion 2007;47:1959–60.
311
[5] Bhatti FA, Salamat N, Nadeem A, Shabiir N. Red cell immunization in beta thalassemia major. J Coll Physicians Surg Pak 2004;14(11):657–60. [6] Bilwani F, Kakepoto GN, Adil SN, Usman M, Hassan F, Khurshid M. Frequency of irregular alloantibodies in patients with thalassemia major: a bi-center study. J Pak Med Assoc 2005;55:563–5. [7] Hassan Khalid, Younus Muhammad, Ikram Nadeem, Naseem Lubna, Zaheer Hassan Abbas. Red cell alloimmunization in repeatedly transfused thalassemia major patients. Int J Path 2004;2(1):16–9. [8] Coles SM, Klein HG, Holland PV. Alloimmunization in two multi transfused patient populations. Transfusion 1981;21:462–6. [9] Sirchia G, Rebulla P, Mascaretti L, et al. The clinical importance of leukocyte depletion in regular erythrocyte transfusions. Vox Sang 1986;51(Suppl. 1):2–8. [10] Blumberg N, Ross K, Avila E, Peck K. Should chronic transfusions be matched for antigens other than ABO and Rho(D)? Vox Sang 1984;47(3):205–8.
Bushra Moiz Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi, Pakistan Tel.: +92 21 4864511x1302; fax: +92 213 4934294. E-mail address: [email protected]