Alloimmunization against Rh and Kell blood groups antigens is the main obstacle for blood transfusion in transfusion dependent thalassemia patients in Iran

Abstract is not required for Editorialis not required for Editorial (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 8 No. 6, June 2017. ISSN – [0976-3198] Int J Case Rep Images 2017;8(6):358–363. www.ijcasereportsandimages.com Dorgalaleh et al. 358 CASE REPORT OPEN ACCESS Alloimmunization against Rh and Kell blood groups antigens is the main obstacle for blood transfusion in transfusion dependent thalassemia patients in Iran Akbar Dorgalaleh, Mohammad Saeed Gholami, Mohammad Shokuhiyan, Mohsen Valikhani, Esmaei Saneei Moghaddam, Majid Naderi ALLOIMMUNIZATION IN THALASSEMIA MAJOR Thalassemia is the most common inherited singlegene disorder, causes by decrease or absence of α-globin or β-globin chain production. The disorder commonly inherited in autosomal recessive manner and is more common in areas with high rate of consanguinity [1–3]. Thalassemia belt is an extensive area which extend from Mediterranean east through Middle-East and India to Southeast Asia and south through Africa. Estimated incidence of thalassemia in this area is varies from 1–20% depend on area. Iran as a Middle-East country with high rate of consanguineous marriage has a considerable number of patients with β-thalassemia major [4–6]. The precise incidence of disorder is not clear in Iran but it was estimated that there are between two and three million beta thalassemia carriers and about 20,000 patients with beta thalassemia major. The main therapeutic choice in these patients is packed red blood cell (pRBC) transfusion. Continuous blood transfusion imposed a number of transfusion related complications, most importantly iron overload and related complications as well as alloimmunization against transfused red blood cell antigens [6–10]. The reported rate of alloimmunization Akbar Dorgalaleh1, Mohammad Saeed Gholami1, Mohammad Shokuhiyan1, Mohsen Valikhani1, Esmaei Saneei Moghaddam2, Majid Naderi3 Affiliations: 1Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran; 2Genetic Research Center in Non-Communicable Disease, Zahedan University of Medical sciences, Zahedan, Iran; 3Iranian Blood Transfusion Organization Research Center, Zahedan, Iran.. Corresponding Author: Akbar Dorgalaleh, Tehran, Iran; Email: dorgalaleha@gmail.com Received: 17 May 2017 Accepted: 18 May 2017 Published: 01 June 2017 among transfused dependent patients with thalassemia varies between 4–50% and has a lower incidence in homologues populations. Some of these alloantibodies are important and even cause severe life-threatening transfusion related hemolytic reactions while others are clinically insignificant. Both of alloantibodies and autoantibodies may decrease survival of transfused pRBC and increase transfusion rate. Such patients may require immunosuppressive drugs, splenectomy as well as other alternative treatments. Therefore, alloimmunization and autoimmunization can significantly affect patients’ quality of life and overall survival [11–13]. ALLOIMMUNIZATION IN THALASSEMIA MAJOR IN IRAN A considerable number of studies were performed in patients with β-thalassemia major in different areas of Iran. The most common used method for detection of alloimmunization, was conventional tube technique (~80%), while gel method was used in minority (~20%) [5–8]. In the majority of studies, in addition to alloantibodies, autoantibody (8 out of 13 studies) (61.5%) also were detected [1, 3, 4, 12]. Among these studies, the rate of autoimmunization ranges from 1–~19% [4, 9]. The rate of alloimmunization varied between ~3–76%. The lower incidence of alloimmunization was reported in Tehran province, while the highest incidence was observed in Isfahan province [6, 9]. Among alloantibodies the majorities are against Rh and Kell blood group systems. The prevalence of alloantibody against, Rh system ranged from 7.5–100% and this prevalence for Kell system varied from 14–60% [3]. Among these studies on Iranian patients, the rate of splenectomy was reported from ~8– 100%. The rate of alloimmunization against these totally splenectomies patients was ~4% (Table 1). In Rh blood group system, most of antibodies directed against, E, C and c antigens respectively, while in Kell blood group system the majority were directed against K antigen (Table 2). EDITO IAL OPEN A CE S

Thalassemia is the most common inherited singlegene disorder, causes by decrease or absence of α-globin or β-globin chain production. The disorder commonly inherited in autosomal recessive manner and is more common in areas with high rate of consanguinity [1][2][3]. Thalassemia belt is an extensive area which extend from Mediterranean east through Middle-East and India to Southeast Asia and south through Africa. Estimated incidence of thalassemia in this area is varies from 1-20% depend on area. Iran as a Middle-East country with high rate of consanguineous marriage has a considerable number of patients with β-thalassemia major [4][5][6]. The precise incidence of disorder is not clear in Iran but it was estimated that there are between two and three million beta thalassemia carriers and about 20,000 patients with beta thalassemia major. The main therapeutic choice in these patients is packed red blood cell (pRBC) transfusion. Continuous blood transfusion imposed a number of transfusion related complications, most importantly iron overload and related complications as well as alloimmunization against transfused red blood cell antigens [6][7][8][9][10]. The reported rate of alloimmunization among transfused dependent patients with thalassemia varies between 4-50% and has a lower incidence in homologues populations. Some of these alloantibodies are important and even cause severe life-threatening transfusion related hemolytic reactions while others are clinically insignificant. Both of alloantibodies and autoantibodies may decrease survival of transfused pRBC and increase transfusion rate. Such patients may require immunosuppressive drugs, splenectomy as well as other alternative treatments. Therefore, alloimmunization and autoimmunization can significantly affect patients' quality of life and overall survival [11][12][13].

ALLOIMMUNIZATION IN THALASSEMIA MAJOR IN IRAN
A considerable number of studies were performed in patients with β-thalassemia major in different areas of Iran. The most common used method for detection of alloimmunization, was conventional tube technique (~80%), while gel method was used in minority (~20%) [5][6][7][8]. In the majority of studies, in addition to alloantibodies, autoantibody (8 out of 13 studies) (61.5%) also were detected [1,3,4,12]. Among these studies, the rate of autoimmunization ranges from 1-~19% [4,9]. The rate of alloimmunization varied between ~3-76%. The lower incidence of alloimmunization was reported in Tehran province, while the highest incidence was observed in Isfahan province [6,9]. Among alloantibodies the majorities are against Rh and Kell blood group systems. The prevalence of alloantibody against, Rh system ranged from 7.5-100% and this prevalence for Kell system varied from 14-60% [3]. Among these studies on Iranian patients, the rate of splenectomy was reported from ~8-100%. The rate of alloimmunization against these totally splenectomies patients was ~4% (Table 1).
In Rh blood group system, most of antibodies directed against, E, C and c antigens respectively, while in Kell blood group system the majority were directed against K antigen ( Table 2).  All of the patients had their spleen removed prior to the time of antibody formation.

COMPARISON BETWEEN ALLOIM-MUNIZATION IN IRAN WITH OTHER COUNTRIES
Similar to Iran the most common antibodies against transfused red blood cells were anti-Rh and anti-Kell antibodies in other countries [14][15][16][17][18][19][20][21][22]. The rate of alloimmunization varies between these countries from ~4% in India and Pakistan to ~75% in Kuwait [16,21,22]. Similar to Iran, conventional tube method is the most commonly used method for antibody detection and identification in other countries [23][24][25][26]. Although as low as 0.7% of autoantibody was reported in other countries, most studies reported a significantly higher incidence of autoimmunization in other countries [18,[22][23][24][25]. In Kell blood group system, the most commonly alloantibodies directed against K antigen [14,[18][19][20]. In Rh blood group system, majority of antibody directed against D, E and C antigens (Table 3). With regards to these studies it seems that alloimmunization and even autoimmunization are a major concern in transfusion dependent thalassemia patients [5,7,22]. In Iranian patients with β-thalassemia major, transfusion related reaction was reported with a prevalence of about 15% in some studies [15,20]. Sometime, in patients with alloimmunization is significant and can have lifethreatening consequences. In emergency situations, appropriate blood selection is really difficult and required sophisticated laboratory investigations that only can be performed in specialized laboratories. In addition to this condition, clinically significant alloantibodies and autoantibodies can affect quality of life of these patients and affect overall survival of patients with β-thalassemia major. To prevent such conditions, its appropriate to use more suitable preventable strategies such as phenotyping of patients prior to beginning blood transfusion and used of relatively complete matched pRBC. Another way to prevent, is application of direct donation instead of random pRBC transfusion that increase the rate of alloimmunization and related consequences.

Acknowledgements
We appreciate all patients with thalassemia that taking part in our researches and improved our knowledge about different aspects of thalassemia.

Author Contributions
Akbar Dorgalaleh -Substantial contributions to conception and design, Acquisition of data, Analysis

Edorium Journals: An introduction
Edorium Journals Team

But why should you publish with Edorium Journals?
In less than 10 words -we give you what no one does.

Vision of being the best
We have the vision of making our journals the best and the most authoritative journals in their respective specialties. We are working towards this goal every day of every week of every month of every year.

Exceptional services
We care for you, your work and your time. Our efficient, personalized and courteous services are a testimony to this.

Editorial Review
All manuscripts submitted to Edorium Journals undergo pre-processing review, first editorial review, peer review, second editorial review and finally third editorial review.

Peer Review
All manuscripts submitted to Edorium Journals undergo anonymous, double-blind, external peer review.

Early View version
Early View version of your manuscript will be published in the journal within 72 hours of final acceptance.

Manuscript status
From submission to publication of your article you will get regular updates (minimum six times) about status of your manuscripts directly in your email.

Favored Author program
One email is all it takes to become our favored author. You will not only get fee waivers but also get information and insights about scholarly publishing.

Institutional Membership program
Join our Institutional Memberships program and help scholars from your institute make their research accessible to all and save thousands of dollars in fees make their research accessible to all.

Our presence
We have some of the best designed publication formats. Our websites are very user friendly and enable you to do your work very easily with no hassle. Something more...
We request you to have a look at our website to know more about us and our services.
We welcome you to interact with us, share with us, join us and of course publish with us.

Invitation for article submission
We sincerely invite you to submit your valuable research for publication to Edorium Journals.

Six weeks
You will get first decision on your manuscript within six weeks (42 days) of submission. If we fail to honor this by even one day, we will publish your manuscript free of charge.*

Four weeks
After we receive page proofs, your manuscript will be published in the journal within four weeks (31 days). If we fail to honor this by even one day, we will publish your manuscript free of charge and refund you the full article publication charges you paid for your manuscript.* This page is not a part of the published article. This page is an introduction to Edorium Journals and the publication services. * Terms and condition apply. Please see Edorium Journals website for more information.