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Frequency of red cell alloimmunization in patients with sickle cell anemia in an Egyptian referral hospital
Transfusion and Apheresis Science 47 (2012) 253–257
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Frequency of red cell alloimmunization in patients with sickle cell anemia in an Egyptian referral hospital Rabab Aly a,⇑, Mohamed R. El-sharnoby b, Adel A. Hagag b a b
Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Pediatrics Department, Faculty of Medicine, Tanta University, Mansoura, Egypt
a r t i c l e
i n f o
Keywords: SCA Alloimmunization Red cell antibodies
a b s t r a c t Introduction: Sickle cell anemia (SCA) is an important public health issue in Tanta, Egypt. Erythrocyte transfusions may reduce the morbidity of SCA, however, they are associated with numerous risks. Among other risk categories, alloimmunization to red cell antigens may result from transfusions. The objective of this study was to explore the frequency of red cell alloantibodies among SCA patients who received regular transfusions. Materials and methods: A total of 42 patients with SCA were included in this study. This work planned to study the presence of alloantibodies to different red cell antigens in multi-transfused SCA patients using the ID card micro-typing system. Clinical and laboratory data were collected and analyzed to find out the frequency, pattern and factors influencing red cell alloimmunization secondary to multiple blood transfusion in these patients. Results: Of a total of 42 SCA patients included in the study, 21.4% of patients developed alloantibodies. The most common alloantibodies were anti-K, anti-E and anti-C. The rate of incidence of these alloantibodies was 7.1%, 4.8% and 4.8%, respectively. There was significant association between alloantibody and the rate of transfused blood. The mean age of patients with and without alloimmunization was 12.0 and 6.2 years. Conclusions: Alloimmunization to minor erythrocyte antigens of variable clinical significance is a frequent finding in transfused SCA patients. Regular screening for red cell alloantibodies would provide better management of these patients. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Red blood cell (RBC) transfusion therapy is a key component in the treatment of patients with sickle cell disease (SCD) [1]. Unfortunately, transfusion carries risks for infectious disease transmission, as well as immunologic and inflammatory sequelae [2]. Among other risk categories, alloimmunization to red cell antigens may result from transfusions [3]. Alloimmunization is a recognized complication of RBC transfusions with consequences including delayed hemolytic transfusion reactions and difficulties in getting compatible blood for future transfusions [4]. With advances now reducing the side effects of transfusion ⇑ Corresponding author. E-mail address: [email protected] (R. Aly). 1473-0502/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.transci.2012.07.014
and several landmark studies over the last decade clearly defining the efficacy of decreasing sickle cell morbidity, the indications for transfusion have increased [5]. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. Some alloantibodies may cause hemolytic transfusion reactions, which limits the possibility of safe transfusion, while others are clinically insignificant. Red cell autoantibodies appear less frequently but can result in hemolysis and difficulty in blood cross-matching [6]. The exact kinetics of alloimmunization are not clear [7,8]. The development of alloantibodies can significantly complicate transfusion therapy and therefore the knowledge of such alloantibodies is essential for selecting appropriate RBC products for transfusion [9]. However, preventive phenotypic matching for common antigens can minimize alloimmunization [10]. Reports indicating that
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R. Aly et al. / Transfusion and Apheresis Science 47 (2012) 253–257
performing just partial phenotype matching to Rh and Kell antigens are useful and effective in decreasing the incidence of alloimmunization [11]. This issue has been controversial and vigorously debated. The main drawbacks are the costs, the time and labor involved in performing extended and even partial RBC phenotyping. However, experience has demonstrated that providing antigen-matched blood prevents alloimmunization as well as other complications for these patients that may outweigh the higher costs of the process. Many studies have shown the importance of providing antigen-matched blood for chronic transfusion patients, such as those with thalassaemia and SCA, in order to decrease the frequency of alloimmunization and its related complications [12]. The causes of alloimmunization in sickle cell patients are not fully understood. However, data suggest that the recipient’s immune status, absence of spleen and difference in the red cell phenotype between donors and recipients are likely to contribute further to the phenomenon [13]. The frequency of alloimmunization in patients with sickle cell anemia has been reported to range from 2.6% to 76%. [14]. The most common alloantibodies reported to be detected include in rank order: anti-E, anti-C, anti-K, followed by anti-Fya, anti-JKb, anti-S and anti-D [15]. The main objective of this study was to assess the frequency of alloimmunization in SCA patients managed in a university hospital in Tanta, in order to provide appropriate recommendations for the care of these patients.
2. Materials and methods This study was conducted over a 3-year period from January 2008 to January 2011 at the Pediatric Department of Tanta University Hospital. Written consent was provided for each patient. A total of 42 SCA patients who received regular blood transfusions were included in the study. They were 22 males and 20 females aged 3–18 years (median age was 8.4 years). The diagnosis of SCD was confirmed by standard Hb electrophoresis, isoelectric focusing, determination of Hb A2 and Hb F, and family studies, when necessary. Clinical transfusion records of 42 SCA patients were analyzed for ethnic background, age at start of transfusion and rate and duration of transfused blood. All patients received fully matched blood for only ABO and Rh (D) antigens. There were no available data on the time from start of transfusion to antibody formation. The practical part of this work aimed at studying the presence of alloantibodies to different red cell antigens in SCA patients using the ID.Card micro-typing system (Gel tear, Switzerland). Dia cell I, II and III were used to screen for the presence of red cell alloantibodies and the Dia panel to identify these alloantibodies. All pre-transfused patients were routinely tested for ABO and Rh D antigen. Screening of the sera for erythrocyte antibodies and identification tests: the idea of this test was to detect alloimmune antibodies formed against any RBC antigen in the tested sera; this was done with two different tests: screening and identification tests. The antibody screening test was done with a combination of three sets of commercial group O red blood cells which had been typed for clinically significant
antigens as well as rare antigens. These three sets are known as Dia cell I, II, III. It was performed for the following antigens: A, B, C, c, D, E, Lea, Leb, K, Fya, Fyb, Jka, JKb, M, N, PI, S and s. 3. Statistical analysis Descriptive statistics, the Mann–Whitney test and Fisher’s exact test were performed and a p-value of less than 0.05 was considered significant. The results were analyzed using the Statistical Package for Social Sciences version 15.0. 4. Results A total of 42 SCA subjects were enrolled for the study. They were regular recipients of blood transfusions. They received ABO and Rh D matched homologous, non-leukodepleted whole blood or packed RBCs. None of our patients had undergone splenectomy. Nine subjects were positive for RBC alloantibodies, thus the prevalence of alloimmunized was 21.4%. A total of 22 (52.4%) study subjects were male while 20 (47.6%) were female. Of 9 alloimmunized patients, 3 patients (33.3%) were males and 6 (66.7%) were females. The characteristics of the SCA patients are summarized in Table 1. The age of the study subjects ranged from 3 to 18 years. The mean age of the alloimmunized subjects was 12.0 ± 2.4 years as against 6.2 ± 2.3 years in non-alloimmunized; the difference in mean age was statistically significant (P = 0.001). The mean duration from first transfusion in alloimmunized and non-alloimmunized SCA patients was 9.0 ± 1.5 and 3.0 ± 1.0 years, respectively, this was statistically significant (P = 0.001). The mean age at first transfusion in alloimmunized and non-alloimmunized SCA patients was 3.5 ± 2.3 and 4.5 ± 2.1 years, respectively; this was statistically non-significant (P = 0.08). Alloimmunized patients received a mean rate of 8.2 ± 1.9 blood transfusions per year, as opposed to 4.1 ± 1.3 transfusions for non-alloimmunized patients (P = 0.01). The ABO blood group distribution among the study patients is summarized in Table 3. Analysis revealed that 23 (54.7%), 10 (23.9%), 7 (16.7%) and 2 (4.7%) subjects were of O, A, B and AB blood group respectively; amongst them 4 (9.5%), 3 (7.1%), 2 (4.8%) subjects of O, A and B blood group, respectively, were alloimmunized. No subjects were Rh D negative. The most common alloantibodies were anti-K (Kell system), anti-E and anti-C (Rhesus system). The incidence of these alloantibodies was 3 (7.1%), 2 (4.8%) and 2 (4.8%), respectively, of the total 42 patients with SCA, however, anti-Le’ and anti-Jk’ was found in one (2.4%) subject each. A profile of the alloimmunized SCA patients is given in Table 2. 5. Discussion Transfusion dependent diseases are characterized by a high alloimmunization frequency and this is highest in
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R. Aly et al. / Transfusion and Apheresis Science 47 (2012) 253–257 Table 1 Profile of SCA patients.
⁄
Non-alloimmunized
Alloimmunized
P value
Age (years) Mean ± SD
4–9 6.2 ± 2.3
9–15 12.0 ± 2.4
0.001⁄
Age at first transfusion (years) Mean ± SD
3.5 ± 2.3
4.5 ± 2.1
0.08
Duration of transfusion (years) Mean ± SD
2–5 3.0 ± 1.0
2–9 9.0 ± 1.5
0.001⁄
Rate of transfusion (units/year) Mean ± SD
4–10 4.1 ± 1.3
4–12 8.2 ± 1.9
0.01⁄
P<0.05 is significant.
Table 2 Profile of alloimmunized SCA patients. Age (years)
Sex
Blood group
Age at first transfusion (years)
Duration of transfusion (years)
Alloantibody specificity
13 11 9 13 12 15 11 12 12
M M M F F F F F F
O A A O O O B A B
3 4 5 5 4 4 2 4 3
8 7 4 7 7 9 9 7 8
Anti-K Anti-E Anti-C Anti-K Anti-K Anti-C Anti-Le Anti-Jk Anti-E
Table 3 The distribution of blood groups among the study patients.
All patients Alloimmunized patients
A n (%)
B n (%)
O n (%)
AB n (%)
10 (23.9%) 3 (7.1%)
7 (16.7%) 2 (4.8%)
23 (54.7%) 4 (9.5%)
2 (4.7%) 0 (0%)
sickle cell patients. There are combined data from many studies on sickle cell patients [11,16,17]. In the present study we examined the common RBC phenotypes among Egyptian’s SCA which have not been previously described. The rate of alloimmunization observed in the present study was 21.4%. Other studies have reported frequencies ranging from 2.6% to 47% [14,18–22]. Other studies presented lower rates of alloimmunization, 7.8% [23] and 6.0% [24] which included patients who were predominantly in the pediatric group. The rate in our study is on the low side of the wide range of frequencies reported in the literature; the highest is in the UK 76% [14], USA 42.9% [25], 47% [15], 34.8 [20] and 34% [19], Taiwan 37% [26] and Kuwait 30% [27]. The alloimmunization frequency in the present study was in accordance with the Greek rate of 21.1% [28]. The relatively low rate found in the present study and other similar studies may be due to the fact that patients were not monitored for RBC antibodies after each transfusion and hence transitory antibodies were probably not detected. Also, low alloimmunization can probably be explained by the similarity in the ethnicity between patients and donors. All of our alloimmunized patients were Egyptian and most of our blood donors were also Egyptian, thereby minimizing the racial differences between donor
and recipient red cell phenotypes which may account for the antibodies that develop in multi-transfused patients [29,30]. A much lower alloimmunization rate (2.6%) was reported in Jamaican SCD patients when transfused in Jamaica, where both donors and recipients are of African origin, than when the transfusion is undertaken in the United Kingdom, where the donors are predominantly Caucasians [25]. This indicates clearly that the frequency of alloimmunization after random multiple blood transfusions diminishes significantly if blood transfusion between donor and recipient is kept within the same ethnic group. All of our patients received compatible blood for ABO, and Rh D. Spanos et al. demonstrated that for prevention of alloimmunization, transfusion of blood matched for the Rh and K antigens resulted in a significant difference in the alloimmunization rate [28]. The risk factors for alloimmunization are complex and involve at least three main contributing elements: the RBC antigenic difference between the blood donor and the recipient, the recipient’s immune status, and the immunomodulatory effect of the allogenic blood transfusion on the recipient’s immune system [7]. A low rate of alloimmunization may be expected when there is homogeneity of RBC antigens between the blood providers and recipients [31].
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In the current study, anti-K was seen most frequently, followed by anti-E and anti-C, which are all potentially hemolytic antibodies. This finding is in accordance with others [18,23,32]. The specificities of the antibodies found in the present study are different from those found in other reports of alloimmunization in SCD [16]. This high rate of these alloantibodies is certainly due to the high immunogenicity of antigens C, D, E and K [33], also to the fact that RBC matching was not routinely employed for all of these antigens, except for antigen D. In the present study, alloimmunization is more frequent in females and some investigators have reported a higher risk for females [34,35]. Older patients were at a higher risk to develop alloimmunization. In another study [18], the rate of alloimmunization in patients younger than 10 years was lower than in other age groups, even after adjusting for the number of transfusions, with similar results observed by others [23,24]. Other than for ethnic mismatching, the chance of alloimmunization is expected to be higher the larger the number of donor exposures [18,19]. In the present study, the risk of developing alloimmunization was associated with the number or the rate of transfusions received, in agreement with the literature [18,23,36]. Controversy exists as to whether limited versus extended red cell phenotyping for ABO and D in addition to other minor blood types in transfusion dependent patients should be done before the patients receive their first matched RBC transfusion. The weight of the published evidence leans heavily on limited phenotyping (ABO, D, C, E and Kell) [7,10,37]. Other than being costly and time consuming, extended phenotyping does not prevent the serious complication of hyper-hemolysis [15]. A recent survey in the USA [38] found that the majority of North American transfusion laboratories do not determine the red cell antigen phenotype of non-alloimmunized sickle disease patients beyond ABO and D. Besides, those laboratories that determine the RBC phenotypes in non-alloimmunized patients with SCD, embark on a limited phenotype protocol, C, E and Kell in addition to ABO and D. Due to high cost, a study from Brazil recommended the use of extended matched transfusions only for patients who have already developed one or more RBC alloantibodies [32]. Issit’s recommendation [29], also follow a similar protocol which includes routine ABO and D typing for all transfusion-dependant patients and reserving further phenotyping only when a patient becomes alloimmunized. Based on the present results and the literature data [11], the RBC should be matched for C, E and K antigens in transfusions administered to patients with SCA. We recommend obtaining an RBC antigen phenotype for all SCA patients who are started on transfusions and providing universal leuko-depleted blood matched for antigens of the ABO, Kell and Rh system.
Conflict of interest This study has not been financed by any research grants and the authors have no personal relationships with other people or organizations that could bias this work.
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[33] Mollison PL, Engelfriet CP, Contreras M. Blood transfusion in clinical medicine. 10th ed. Oxford, UK: Blackwell Science; 1997. [34] Orlina AR, Unger PJ, Koshy M. Post-transfusion alloimmunization in patients with sickle cell disease. Am J Hematol 1978;5:101–6. [35] Reisner EG, Kostyu DD, Phillips G, Walker C, Dawson V. Alloantibody responses in multiply transfused sickle cell patients. Tissue Antigens 1987;30:161–6. [36] Cox JV, Steane E, Cunningham G, Frenkel EP. Risk of alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease. Arch Intern Med 1988;148:2485–9. [37] 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. [38] Osbey M, Shulma IA. Phenotype matching of donor red blood cell units for nonalloimmunized sickle cell disease patients: a survey of 1182 North American laboratories. Arch Pathol Lab Med 2005;129(2):190–3.
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Frequency of red cell alloimmunization in patients with sickle cell anemia in an Egyptian referral hospital Rabab Aly a,⇑, Mohamed R. El-sharnoby b, Adel A. Hagag b a b
Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Pediatrics Department, Faculty of Medicine, Tanta University, Mansoura, Egypt
a r t i c l e
i n f o
Keywords: SCA Alloimmunization Red cell antibodies
a b s t r a c t Introduction: Sickle cell anemia (SCA) is an important public health issue in Tanta, Egypt. Erythrocyte transfusions may reduce the morbidity of SCA, however, they are associated with numerous risks. Among other risk categories, alloimmunization to red cell antigens may result from transfusions. The objective of this study was to explore the frequency of red cell alloantibodies among SCA patients who received regular transfusions. Materials and methods: A total of 42 patients with SCA were included in this study. This work planned to study the presence of alloantibodies to different red cell antigens in multi-transfused SCA patients using the ID card micro-typing system. Clinical and laboratory data were collected and analyzed to find out the frequency, pattern and factors influencing red cell alloimmunization secondary to multiple blood transfusion in these patients. Results: Of a total of 42 SCA patients included in the study, 21.4% of patients developed alloantibodies. The most common alloantibodies were anti-K, anti-E and anti-C. The rate of incidence of these alloantibodies was 7.1%, 4.8% and 4.8%, respectively. There was significant association between alloantibody and the rate of transfused blood. The mean age of patients with and without alloimmunization was 12.0 and 6.2 years. Conclusions: Alloimmunization to minor erythrocyte antigens of variable clinical significance is a frequent finding in transfused SCA patients. Regular screening for red cell alloantibodies would provide better management of these patients. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Red blood cell (RBC) transfusion therapy is a key component in the treatment of patients with sickle cell disease (SCD) [1]. Unfortunately, transfusion carries risks for infectious disease transmission, as well as immunologic and inflammatory sequelae [2]. Among other risk categories, alloimmunization to red cell antigens may result from transfusions [3]. Alloimmunization is a recognized complication of RBC transfusions with consequences including delayed hemolytic transfusion reactions and difficulties in getting compatible blood for future transfusions [4]. With advances now reducing the side effects of transfusion ⇑ Corresponding author. E-mail address: [email protected] (R. Aly). 1473-0502/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.transci.2012.07.014
and several landmark studies over the last decade clearly defining the efficacy of decreasing sickle cell morbidity, the indications for transfusion have increased [5]. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. Some alloantibodies may cause hemolytic transfusion reactions, which limits the possibility of safe transfusion, while others are clinically insignificant. Red cell autoantibodies appear less frequently but can result in hemolysis and difficulty in blood cross-matching [6]. The exact kinetics of alloimmunization are not clear [7,8]. The development of alloantibodies can significantly complicate transfusion therapy and therefore the knowledge of such alloantibodies is essential for selecting appropriate RBC products for transfusion [9]. However, preventive phenotypic matching for common antigens can minimize alloimmunization [10]. Reports indicating that
254
R. Aly et al. / Transfusion and Apheresis Science 47 (2012) 253–257
performing just partial phenotype matching to Rh and Kell antigens are useful and effective in decreasing the incidence of alloimmunization [11]. This issue has been controversial and vigorously debated. The main drawbacks are the costs, the time and labor involved in performing extended and even partial RBC phenotyping. However, experience has demonstrated that providing antigen-matched blood prevents alloimmunization as well as other complications for these patients that may outweigh the higher costs of the process. Many studies have shown the importance of providing antigen-matched blood for chronic transfusion patients, such as those with thalassaemia and SCA, in order to decrease the frequency of alloimmunization and its related complications [12]. The causes of alloimmunization in sickle cell patients are not fully understood. However, data suggest that the recipient’s immune status, absence of spleen and difference in the red cell phenotype between donors and recipients are likely to contribute further to the phenomenon [13]. The frequency of alloimmunization in patients with sickle cell anemia has been reported to range from 2.6% to 76%. [14]. The most common alloantibodies reported to be detected include in rank order: anti-E, anti-C, anti-K, followed by anti-Fya, anti-JKb, anti-S and anti-D [15]. The main objective of this study was to assess the frequency of alloimmunization in SCA patients managed in a university hospital in Tanta, in order to provide appropriate recommendations for the care of these patients.
2. Materials and methods This study was conducted over a 3-year period from January 2008 to January 2011 at the Pediatric Department of Tanta University Hospital. Written consent was provided for each patient. A total of 42 SCA patients who received regular blood transfusions were included in the study. They were 22 males and 20 females aged 3–18 years (median age was 8.4 years). The diagnosis of SCD was confirmed by standard Hb electrophoresis, isoelectric focusing, determination of Hb A2 and Hb F, and family studies, when necessary. Clinical transfusion records of 42 SCA patients were analyzed for ethnic background, age at start of transfusion and rate and duration of transfused blood. All patients received fully matched blood for only ABO and Rh (D) antigens. There were no available data on the time from start of transfusion to antibody formation. The practical part of this work aimed at studying the presence of alloantibodies to different red cell antigens in SCA patients using the ID.Card micro-typing system (Gel tear, Switzerland). Dia cell I, II and III were used to screen for the presence of red cell alloantibodies and the Dia panel to identify these alloantibodies. All pre-transfused patients were routinely tested for ABO and Rh D antigen. Screening of the sera for erythrocyte antibodies and identification tests: the idea of this test was to detect alloimmune antibodies formed against any RBC antigen in the tested sera; this was done with two different tests: screening and identification tests. The antibody screening test was done with a combination of three sets of commercial group O red blood cells which had been typed for clinically significant
antigens as well as rare antigens. These three sets are known as Dia cell I, II, III. It was performed for the following antigens: A, B, C, c, D, E, Lea, Leb, K, Fya, Fyb, Jka, JKb, M, N, PI, S and s. 3. Statistical analysis Descriptive statistics, the Mann–Whitney test and Fisher’s exact test were performed and a p-value of less than 0.05 was considered significant. The results were analyzed using the Statistical Package for Social Sciences version 15.0. 4. Results A total of 42 SCA subjects were enrolled for the study. They were regular recipients of blood transfusions. They received ABO and Rh D matched homologous, non-leukodepleted whole blood or packed RBCs. None of our patients had undergone splenectomy. Nine subjects were positive for RBC alloantibodies, thus the prevalence of alloimmunized was 21.4%. A total of 22 (52.4%) study subjects were male while 20 (47.6%) were female. Of 9 alloimmunized patients, 3 patients (33.3%) were males and 6 (66.7%) were females. The characteristics of the SCA patients are summarized in Table 1. The age of the study subjects ranged from 3 to 18 years. The mean age of the alloimmunized subjects was 12.0 ± 2.4 years as against 6.2 ± 2.3 years in non-alloimmunized; the difference in mean age was statistically significant (P = 0.001). The mean duration from first transfusion in alloimmunized and non-alloimmunized SCA patients was 9.0 ± 1.5 and 3.0 ± 1.0 years, respectively, this was statistically significant (P = 0.001). The mean age at first transfusion in alloimmunized and non-alloimmunized SCA patients was 3.5 ± 2.3 and 4.5 ± 2.1 years, respectively; this was statistically non-significant (P = 0.08). Alloimmunized patients received a mean rate of 8.2 ± 1.9 blood transfusions per year, as opposed to 4.1 ± 1.3 transfusions for non-alloimmunized patients (P = 0.01). The ABO blood group distribution among the study patients is summarized in Table 3. Analysis revealed that 23 (54.7%), 10 (23.9%), 7 (16.7%) and 2 (4.7%) subjects were of O, A, B and AB blood group respectively; amongst them 4 (9.5%), 3 (7.1%), 2 (4.8%) subjects of O, A and B blood group, respectively, were alloimmunized. No subjects were Rh D negative. The most common alloantibodies were anti-K (Kell system), anti-E and anti-C (Rhesus system). The incidence of these alloantibodies was 3 (7.1%), 2 (4.8%) and 2 (4.8%), respectively, of the total 42 patients with SCA, however, anti-Le’ and anti-Jk’ was found in one (2.4%) subject each. A profile of the alloimmunized SCA patients is given in Table 2. 5. Discussion Transfusion dependent diseases are characterized by a high alloimmunization frequency and this is highest in
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R. Aly et al. / Transfusion and Apheresis Science 47 (2012) 253–257 Table 1 Profile of SCA patients.
⁄
Non-alloimmunized
Alloimmunized
P value
Age (years) Mean ± SD
4–9 6.2 ± 2.3
9–15 12.0 ± 2.4
0.001⁄
Age at first transfusion (years) Mean ± SD
3.5 ± 2.3
4.5 ± 2.1
0.08
Duration of transfusion (years) Mean ± SD
2–5 3.0 ± 1.0
2–9 9.0 ± 1.5
0.001⁄
Rate of transfusion (units/year) Mean ± SD
4–10 4.1 ± 1.3
4–12 8.2 ± 1.9
0.01⁄
P<0.05 is significant.
Table 2 Profile of alloimmunized SCA patients. Age (years)
Sex
Blood group
Age at first transfusion (years)
Duration of transfusion (years)
Alloantibody specificity
13 11 9 13 12 15 11 12 12
M M M F F F F F F
O A A O O O B A B
3 4 5 5 4 4 2 4 3
8 7 4 7 7 9 9 7 8
Anti-K Anti-E Anti-C Anti-K Anti-K Anti-C Anti-Le Anti-Jk Anti-E
Table 3 The distribution of blood groups among the study patients.
All patients Alloimmunized patients
A n (%)
B n (%)
O n (%)
AB n (%)
10 (23.9%) 3 (7.1%)
7 (16.7%) 2 (4.8%)
23 (54.7%) 4 (9.5%)
2 (4.7%) 0 (0%)
sickle cell patients. There are combined data from many studies on sickle cell patients [11,16,17]. In the present study we examined the common RBC phenotypes among Egyptian’s SCA which have not been previously described. The rate of alloimmunization observed in the present study was 21.4%. Other studies have reported frequencies ranging from 2.6% to 47% [14,18–22]. Other studies presented lower rates of alloimmunization, 7.8% [23] and 6.0% [24] which included patients who were predominantly in the pediatric group. The rate in our study is on the low side of the wide range of frequencies reported in the literature; the highest is in the UK 76% [14], USA 42.9% [25], 47% [15], 34.8 [20] and 34% [19], Taiwan 37% [26] and Kuwait 30% [27]. The alloimmunization frequency in the present study was in accordance with the Greek rate of 21.1% [28]. The relatively low rate found in the present study and other similar studies may be due to the fact that patients were not monitored for RBC antibodies after each transfusion and hence transitory antibodies were probably not detected. Also, low alloimmunization can probably be explained by the similarity in the ethnicity between patients and donors. All of our alloimmunized patients were Egyptian and most of our blood donors were also Egyptian, thereby minimizing the racial differences between donor
and recipient red cell phenotypes which may account for the antibodies that develop in multi-transfused patients [29,30]. A much lower alloimmunization rate (2.6%) was reported in Jamaican SCD patients when transfused in Jamaica, where both donors and recipients are of African origin, than when the transfusion is undertaken in the United Kingdom, where the donors are predominantly Caucasians [25]. This indicates clearly that the frequency of alloimmunization after random multiple blood transfusions diminishes significantly if blood transfusion between donor and recipient is kept within the same ethnic group. All of our patients received compatible blood for ABO, and Rh D. Spanos et al. demonstrated that for prevention of alloimmunization, transfusion of blood matched for the Rh and K antigens resulted in a significant difference in the alloimmunization rate [28]. The risk factors for alloimmunization are complex and involve at least three main contributing elements: the RBC antigenic difference between the blood donor and the recipient, the recipient’s immune status, and the immunomodulatory effect of the allogenic blood transfusion on the recipient’s immune system [7]. A low rate of alloimmunization may be expected when there is homogeneity of RBC antigens between the blood providers and recipients [31].
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In the current study, anti-K was seen most frequently, followed by anti-E and anti-C, which are all potentially hemolytic antibodies. This finding is in accordance with others [18,23,32]. The specificities of the antibodies found in the present study are different from those found in other reports of alloimmunization in SCD [16]. This high rate of these alloantibodies is certainly due to the high immunogenicity of antigens C, D, E and K [33], also to the fact that RBC matching was not routinely employed for all of these antigens, except for antigen D. In the present study, alloimmunization is more frequent in females and some investigators have reported a higher risk for females [34,35]. Older patients were at a higher risk to develop alloimmunization. In another study [18], the rate of alloimmunization in patients younger than 10 years was lower than in other age groups, even after adjusting for the number of transfusions, with similar results observed by others [23,24]. Other than for ethnic mismatching, the chance of alloimmunization is expected to be higher the larger the number of donor exposures [18,19]. In the present study, the risk of developing alloimmunization was associated with the number or the rate of transfusions received, in agreement with the literature [18,23,36]. Controversy exists as to whether limited versus extended red cell phenotyping for ABO and D in addition to other minor blood types in transfusion dependent patients should be done before the patients receive their first matched RBC transfusion. The weight of the published evidence leans heavily on limited phenotyping (ABO, D, C, E and Kell) [7,10,37]. Other than being costly and time consuming, extended phenotyping does not prevent the serious complication of hyper-hemolysis [15]. A recent survey in the USA [38] found that the majority of North American transfusion laboratories do not determine the red cell antigen phenotype of non-alloimmunized sickle disease patients beyond ABO and D. Besides, those laboratories that determine the RBC phenotypes in non-alloimmunized patients with SCD, embark on a limited phenotype protocol, C, E and Kell in addition to ABO and D. Due to high cost, a study from Brazil recommended the use of extended matched transfusions only for patients who have already developed one or more RBC alloantibodies [32]. Issit’s recommendation [29], also follow a similar protocol which includes routine ABO and D typing for all transfusion-dependant patients and reserving further phenotyping only when a patient becomes alloimmunized. Based on the present results and the literature data [11], the RBC should be matched for C, E and K antigens in transfusions administered to patients with SCA. We recommend obtaining an RBC antigen phenotype for all SCA patients who are started on transfusions and providing universal leuko-depleted blood matched for antigens of the ABO, Kell and Rh system.
Conflict of interest This study has not been financed by any research grants and the authors have no personal relationships with other people or organizations that could bias this work.
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