|Year : 2021 | Volume
| Issue : 2 | Page : 237-239
Alloimmunization to minor red cell antigen leading to massive hemolysis in newly diagnosed thalassemia intermedia
Satyam Arora1, Ravi Shankar2, Seema Dua1, Nita Radhakrishnan2
1 Department of Transfusion Medicine and Blood Bank, Super Speciality Pediatric Hospital and Post Graduate Teaching Institute, Noida, Uttar Pradesh, India
2 Department of Pediatric Hematology Oncology, Super Speciality Pediatric Hospital and Post Graduate Teaching Institute, Noida, Uttar Pradesh, India
|Date of Submission||05-Jan-2021|
|Date of Decision||04-Jun-2021|
|Date of Acceptance||04-May-2021|
|Date of Web Publication||30-Nov-2021|
Dr. Nita Radhakrishnan
Department of Pediatric Hematology Oncology, Super Speciality Pediatric Hospital and Post Graduate Teaching Institute, Noida, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Alloimmunization to red cell antigens is a taxing complication of thalassemia major and intermedia patients who receive routine blood transfusions. The data on alloimmunization in beta-thalassemia are sparse from developing countries. The risk of alloimmunization is higher in thalassemia patients who received their first transfusion after the age of 3 years. We describe the presentation and outcome of a 4.5-year-old girl who presented with massive hemolysis following the first transfusion received following the diagnosis of beta-thalassemia intermedia. Despite best efforts with all available therapeutic modalities, hemolysis could not be controlled and she succumbed to the illness. The case is being presented as such severe hemolysis caused by alloimmunization to a blood group antigen is rare and posed a challenge for both diagnosis and treatment.
Keywords: Alloimmunization, hemolysis, thalassemia
|How to cite this article:|
Arora S, Shankar R, Dua S, Radhakrishnan N. Alloimmunization to minor red cell antigen leading to massive hemolysis in newly diagnosed thalassemia intermedia. Glob J Transfus Med 2021;6:237-9
|How to cite this URL:|
Arora S, Shankar R, Dua S, Radhakrishnan N. Alloimmunization to minor red cell antigen leading to massive hemolysis in newly diagnosed thalassemia intermedia. Glob J Transfus Med [serial online] 2021 [cited 2022 May 26];6:237-9. Available from: https://www.gjtmonline.com/text.asp?2021/6/2/237/331609
| Introduction|| |
Alloimmunization to red cell antigens is a challenging complication of thalassemia major and intermedia patients who receive routine blood transfusions. It causes immediate and delayed transfusion reactions which can often be fatal. The knowledge of risk factors for alloimmunization is vital as prevention is the most effective intervention. The data on alloimmunization in beta-thalassemia are sparse from developing countries.,,,, Most studies mention the prevalence data; literature on management of alloimmunization is mainly anecdotal, with no established guidelines to manage these difficult patients. In the current article, we describe the experience of managing a difficult case of alloimmunization that developed following a single red cell transfusion in a patient with nontransfusion dependent thalassemia (NTDT). The development of this complication changed the outcome of this condition which would have otherwise been relatively favorable.
| Case Report|| |
A 4.5-year-old girl was evaluated for fever and cough at a pediatric hospital in Uttar Pradesh, India, where she was found to have severe anemia (Hb: 4.5 g/dl) with features of cardiac failure. This was her first presentation with anemia and her parents denied any prior transfusions. On examination, she was severely pale and has moderate splenomegaly. She was promptly admitted and given packed red blood cell transfusion (PRBC) after evaluation for beta-thalassemia. HPLC was sent as part of evaluation which was suggestive of homozygous beta-thalassemia. In view of the late clinical presentation and no prior transfusions, she was diagnosed as Beta-Thalassemia Intermedia (NTDT). One week after this blood transfusion, she presented to the same center with recurrence of anemia and respiratory distress. There was no history of red/cola-colored urine, jaundice, fever, or cough. At this presentation, she was found to be hypoxic, severely pale, and when PRBC was ordered, blood bank reported difficulty in crossmatching of blood. She was subsequently transfused to the best matched unit and referred to our center. She was also given one dose of injectable methylprednisolone (20 mg/kg/dose) before transfer.
She presented to us in severe respiratory distress, saturation in room air of 75%–80%, hemoglobin of 1.6 g/dl, and hepatosplenomegaly. Direct Coombs test was positive. The screening for allo and autoantibody was positive. Three cell screening panel was positive with variable reaction strength. Immunohematology evaluation was done to rule out auto and allo antibodies resulting in immune hemolysis. On antibody identification, the specificity of alloantibody was against Kidd B antigen (anti-Jkb) with a titer of 1:16. The anti-Kidd B antibody could have been the reason of the accelerated hemolysis in this case, and the picture was more in the favor of a patient presenting with DHTR.
She was again transfused the best matched (Kidd B antigen negative) leukoreduced PRBC which was transfused along with methylprednisolone for 2 more days followed by oral prednisolone at 2 mg/kg/day. She stabilized (respiratory rate and O2 saturation in room air normalized) and was discharged at a hemoglobin of 7 g/dl. Ten days later, she was brought with recurrence of the same symptoms. Hemoglobin had again dropped to 2 g/dl, and during this admission, she received intravenous immunoglobulin (IVIG) at 1 g/kg as a single dose. However, hemolysis continued and she continued to be hypoxic requiring oxygen with nasal prongs at 2–3 L/min. Over the next 2 weeks, she received another pulse of methylprednisolone, repeat dose of IVIG at 1 g/kg/dose, and one dose of rituximab (375 mg/m2) in view of persistent active severe hemolysis requiring oxygen transfusion. On this visit, her alloadsorption was done, and results indicated the presence of another alloantibody along with anti-Kidd. The second antibody was against Rh blood group antigen (anti-c) but could not be confirmed due to lack of appropriate select cells.
She did not respond to any of the immunosuppressive given and succumbed to the illness almost a month after the initial presentation.
| Discussion|| |
Alloimmunization to red cell antigens is a known complication that occurs in patients with hemoglobinopathies who receive regular transfusions. The risk of alloimmunization ranges from 5.6% to 23% based on published literature from Asia.,,,, The wide range in the prevalence could be because of differences in the sensitivity of reagents used and the heterogeneity in patient age and genetic pool. Anti-E, anti-C, and anti-Kell alloantibodies account for 80% of the alloantibodies observed. About 5%–10% of patients can present with alloantibodies against rare red cell antigens or unidentified antigens. The risk of alloimmunization is much higher (up to 50%) in patients who begin transfusion after 3 years of age. Other factors known to affect antibody production include genetic background, patient's immune status, and the transfusion frequency. This compromises their transfusion therapy to a great extent. Hence, it is highly recommended that patients should have extended red cell antigen typing for C, c, E, e, and Kell antigens before the first transfusion so that the identification of antibodies if they arise is easier. It is recommended to do prophylactic antigen matching for Rh (C, e, E, e) and Kell antigens as they account for most of the alloantibodies in Asians. Furthermore, regular screening for antibody detection can identify them early before they become clinically significant.
Although NTDT is less severe than transfusion-dependent thalassemia, the associated complications can be severe, and quality of life may actually be more impaired in patients with NTDT. Autoimmune hemolytic anemia occurs more frequently in patients who begin transfusion therapy later in life and should be carefully considered before instituting transfusion therapy for teenagers and adults with thalassemia intermedia. The risk of alloimmunization is highest in minimally transfused and newly transfused patients. Initiation of transfusion at an early age is thought to reduce the risk of alloimmunization. Hence, the alloimmunization is more commonly seen among thalassemia intermedia than in thalassemia major.
The risk of alloimmunization can be minimized by extended genotype and antibody screening, and the use of fully phenotype-matched blood should be given. Concomitant administration of steroids for 3–5 days as prophylaxis against alloimmunization has been reported, but the efficacy of this intervention is controversial. Hemolytic reactions in these patients can still be avoided by:
- The use of optimal methods for identifying the patients and labeling of the sample when blood is obtained for crossmatch
- Proper linkage of the sample to the donor unit in the blood bank
- Adherence to standard protocols for screening for antibodies and carrying out the necessary full crossmatching of donor units and
- Use of multiple patient identifiers before transfusing the blood. In many transfusion units, two staff members check the identification of the unit and the recipient before beginning the transfusion.
Steroids, immunosuppressive drugs, and IVIG are used for the clinical management of this situation although they may give little benefit. Some patients have also been treated with rituximab, but the effectiveness of its use in this situation is presently not well defined.
The challenging part of this case was initial differentiation of cause of hemolysis, which in this case was due to delayed hemolytic transfusion reaction resulting from 2 incompatible unit transfusion. Another was determining complete Rh and Kell phenotyping of the patient when she presented to us. As she had already received transfusions, hence, we were not able to phenotype her as well as autoadsorption was not possible. The second antibody could have been an alloantibody or an autoantibody, as most of the autoantibodies behave like antibodies against Rh antigens.
Our case was a rare presentation of massive hemolysis following the very first transfusion in a newly diagnosed patient of thalassemia. The child had alloimmunization with minor antigen (Kidd [B] antigen [anti-Jkb]), where the best of the management failed to stop hemolysis. Such rare presentations will always pose a challenge for the medical community to ponder over the possibilities beyond current knowledge and practices.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Guidelines for the Clinical Management of Thalassaemia [Internet]. 2nd
Revised ed. Nicosia (CY): Thalassaemia International Federation; 2008.
Chaudhari CN. Red cell alloantibodies in multiple transfused thalassaemia patients. Med J Armed Forces India 2011;67:34-7.
Jain R, Choudhury N, Chudgar U, Harimoorthy V, Desai P, Perkins J, et al.
Detection and identification of red cell alloantibodies in multiply transfused thalassemia major patients: A prospective study. Indian J Hematol Blood Transfus 2014;30:291-6.
Jariwala K, Mishra K, Ghosh K. Comparative study of alloimmunization against red cell antigens in sickle cell disease & thalassaemia major patients on regular red cell transfusion. Indian J Med Res 2019;149:34-40.
] [Full text]
Bhuva DK, Vachhani JH. Red cell alloimmunization in repeatedly transfused patients. Asian J Transfus Sci 2017;11:115-20.
] [Full text]
Datta SS, Mukherjee S, Talukder B, Bhattacharya P, Mukherjee K. Frequency of red cell alloimmunization and autoimmunization in thalassemia patients: A report from Eastern India. Adv Hematol 2015;2015:610931.
Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A. Guidelines for the Clinical Management of Thalassaemia. 2nd
ed., Ch. 1. Genetic Basis and Pathophysiology. Nicosia (CY): Thalassaemia International Federation; 2008. p. 25.
Musallam KM, Khoury B, Abi-Habib R, Bazzi L, Succar J, Halawi R, et al.
Health-related quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: New insights. Eur J Haematol 2011;87:73-9.
Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT) [Internet]. Weatherall D, editor. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Link for reference 8: https://pubmed.ncbi.nlm.nih.gov/24672826/
Chou ST, Liem RI, Thompson AA. Challenges of alloimmunization in patients with haemoglobinopathies. Br J Haematol 2012;159:394-404.