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Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 144-148

Transfusion challenges and use of best match blood transfusion in autoimmune hemolytic anemia patients: Experience from a Tertiary Care Hospital of South India

Department of Transfusion Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Submission02-May-2022
Date of Decision03-Aug-2022
Date of Acceptance10-Aug-2022
Date of Web Publication5-Nov-2022

Correspondence Address:
Dibyajyoti Sahoo
Department of Transfusion Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/gjtm.gjtm_39_22

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Background and Objectives: In autoimmune hemolytic anemia (AIHA) patients, there is decreased survival of red blood cells (RBCs) because of increased destruction by patients' autoantibodies. Due to decreased survival of RBCs, there is an increase in erythropoiesis and other biochemical parameters of hemolysis. One of the vital tests in AIHA is direct Coombs test (DCT). In this study, we share our experience on the difficulties faced by us during the compatibility testing and providing transfusion support to these patients. Methods: This is a retrospective study done in the department of transfusion medicine in a tertiary care hospital of South India. Patients from January 2020 to March 2021 with the diagnosis of AIHA requiring transfusion were included in this study. A total of 136 patients with positive DCT with AIHA diagnosis requiring transfusion support were included in our study. Results: Out of 136 cases, 58% (n=79) of patients had incompatibility during cross matching while in 42% (n=57) had cross matched compatible unit. In all incompatible cases best match blood was transfused. Most transfusions were done for patients with DCT Grade 4+. Out of 45 patients with mixed AIHA, 40 (88.8%) patients required a transfusion (P < 0.05). Of that 104 patients with transfusion support, 66 (63%) were with primary AIHA and 38 (36.04%) with secondary AIHA. Conclusion: It is tough and challenging to get compatible units in AIHA patients. Best-matched blood is useful when transfusion becomes essential during life-threatening anemia.

Keywords: Autoantibody, autoimmune hemolytic anemia, best-matched blood, least incompatible blood, transfusion support

How to cite this article:
Sahoo D, Anuragaa S, Basavarajegowda A, Kulkarni RG. Transfusion challenges and use of best match blood transfusion in autoimmune hemolytic anemia patients: Experience from a Tertiary Care Hospital of South India. Glob J Transfus Med 2022;7:144-8

How to cite this URL:
Sahoo D, Anuragaa S, Basavarajegowda A, Kulkarni RG. Transfusion challenges and use of best match blood transfusion in autoimmune hemolytic anemia patients: Experience from a Tertiary Care Hospital of South India. Glob J Transfus Med [serial online] 2022 [cited 2023 Mar 28];7:144-8. Available from: https://www.gjtmonline.com/text.asp?2022/7/2/144/360482

  Introduction Top

Autoimmune hemolytic anemia (AIHA) is the clinical condition in which antibodies of immunoglobulin G (IgG) and/or immunoglobulin M bind to red cell surface antigens and initiate red cell destruction through the complement system and the reticuloendothelial system. In AIHA, there is decreased survival of red blood cells (RBCs) due to increased destruction by the patient's autoantibodies.[1] Direct Coombs test (DCT) is an essential diagnostic test for patients suspecting to have hemolysis with increased laboratory parameters of in vivo hemolysis such as increased indirect bilirubin, lactate dehydrogenase (LDH), reticulocyte, and decreased hemoglobin (Hb).[2] When the destruction is severe and the patient's marrow cannot compensate for the loss, anemia develops. With increasing anemia, the patient becomes clinically symptomatic with cardiopulmonary symptoms because of decreased oxygen-carrying symptoms by the RBC. In these conditions, the patient needs an RBC transfusion. Few AIHA patients arrive in the emergency department with anemia in failure symptoms and an urgent need for a transfusion.[3] Sometimes, it is impossible to get a compatible unit; in those cases, the least incompatible or best match blood is tried.[4] No patient should be denied blood transfusion during severe hemolysis because of incompatibility issues due to autoantibodies. It is always better to transfuse the patient with the best match unit when transfusion is needed, and then, the patient can be started with other treatment modalities. Only transfusion support can help these patients in life-threatening anemia.

Various difficulties are encountered during the pretransfusion testing. There is an increasing turnaround time (TAT) for these cases. The grade of DCT is also significant.[5] The grade of DCT also correlates with the in vivo hemolysis.[5] As more autoantibodies are coated on the RBC surface, the strength of DCT also increases, indirectly indicating hemolysis. AIHA patients may be transfused previously, which would have led to the formation of alloantibody. The presence of alloantibody makes the immunohematology work up even more complex, and it is essential to give the patient an antigen-negative unit. The aim of the present study is to assess various transfusion challenges in AIHA patients and to analyze the utility of best-matched blood in these patients.

  Materials and Methods Top

This is a retrospective study done in the department of transfusion medicine in a tertiary care hospital of South India. All patient details were obtained from hospital records and all laboratory values from the hospital information system. All patient samples were sent under the provisional diagnosis of anemia, suspecting primary or secondary AIHA. Patients from January 2020 to March 2021 with the diagnosis of AIHA requiring transfusion were included in this study. During the study period, a total of 136 patients were registered with us with the diagnosis of AIHA requiring blood transfusion. All of them had positive DCT and clinical and laboratory features of hemolysis.

Before going for a compatibility test, immunohematology workup was done in all cases. This workup includes blood grouping, DCT, indirect Coombs test (ICT), auto control, antibody screening, and antibody identification. In cases of blood group discrepancy, steps were initiated to resolve it before cross-matching. After identifying the patient blood group, DCT was performed using a Coombs card containing polyspecific antihuman globulin (AHG) (IgG + C3d) according to the manufacturer's instruction (Bio-Rad Diagnostics, Switzerland). In positive DCT, monospecific test for IgG and C3d was done. Thermal amplitude was performed at 4°C, 24°C, and 37°C with the patient's cell and serum. In cases where transfusion was indicated compatibility test was done. Patients with incompatible cross-match having history of previous transfusion, transplantation or pregnancy; further immunohematological workup was done to rule out the presence of alloantibodies. This includes 3 cell panel, 11 cell panel, autoabsorption, elution etc.

In patients who had only autoantibody (no alloantibody) with cross-match incompatible, six units of the same blood group were cross-matched to find the least incompatible/best-matched blood. When the patient had both alloantibody and autoantibody, cross-matching was done with six antigen-negative units (corresponding to the alloantibody) of the same blood group. When the degree of incompatibility is higher than 3+ or more than auto control, six units were cross-matched to get a compatible or the best match unit. All cross-matches were done in column agglutination technique using gel technology using polyspecific AHG card.

  Results Top

Request for transfusion was based on the degree of hemolysis, clinical condition, diagnosis, and patient comorbidities. For certain clinically stable AIHA patients, there was no requirement of transfusion. Due to severe anemia, comorbidities, and medical conditions, three units were transfused for a few patient. Compatibility problem was present in more than half of the patients. Out of 136 cases, 79 of patients had incompatibility during cross matching while in 57 had cross match compatible unit. In all incompatible cases best match blood was transfused. There was no adverse reactions following transfusion. Most transfusion was done for patients with DCT Grade 4+ [Table 1]. Patients with mixed AIHA needed maximum transfusion support. Out of 45 patients with mixed AIHA, 40 (88.8%) patients required a transfusion (P < 0.05). In cold AIHA, 12 (85.7%) patients and warm 52 (67.53%) patients needed transfusion support [Figure 1]. Out of the 104 (76.78%) patients who needed transfusion support, 35 (33.72%) patients got compatible units, and the remaining 69 (66.27%) patients were tried with best-matched units [Figure 2]. Out of these 104 patients with transfusion support, 66 (63%) were with primary AIHA and 38 (36.04%) with secondary AIHA. For 32 (23.2%) patients, there was no transfusion requirement. Sixty-nine patients (51%) needed only one unit for transfusion. Thirty-one patients (22%) needed two units, and four patients (3%) required three units for transfusion. Two of our patients expired, of which one needed two units of transfusion and the other did not need a transfusion. More number of units transfused were with patients with mixed AIHA.
Figure 1: Transfusion support in different types of AIHA patients. AIHA: Autoimmune hemolytic anemia

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Figure 2: Compatible units for different AIHA patients. AIHA: Autoimmune hemolytic anemia

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Table 1: Transfusion details of autoimmune hemolytic anemia patients

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Laboratory values of indirect bilirubin and LDH were obtained for every patient. The median value of indirect bilirubin was 1.5 mg/dl. The minimum value was 0.17, and the highest value was 19.78 in a sepsis patient. Fifty-six patients had indirect bilirubin of more than 1.5 mg/dl. Out of 56 patients, 49 (87.5%) had DCT Grade 4+. Patients with LDH values <500 IU were considered to have less hemolysis and more than 500 with more degree of hemolysis. A total of 67 patients had LDH of more than 500 IU.

  Discussion Top

In our study, out of 136 patients, 57 patients got the compatible unit, and the remaining 79 patients were tried with the best match unit. Thirty-two of our patients did not need a transfusion. One hundred four of our patients required transfusion support. Most of the patients (69, 50%) required one-unit transfusion. The reason for this probably clinicians would be reluctant not to transfuse more because of incompatibility issues. This also shows that with one transfusion unit, most patients can be managed. Patients with mixed AIHA needed maximum transfusion support. Mixed AIHA has both warm and cold antibodies, and they have many and different classes of immunoglobulins, including IgA coated on their RBC surface. This may lead to severe hemolysis, and the need for transfusion arises. A study by Das et al. also shows that patients with mixed AIHA presented with severe hemolysis and needed an urgent transfusion.[6] Next to mixed AIHA cases, cold AIHA needed more transfusion. Ninety percent of cold AIHA needed transfusion support in our study. Complement activation and complement-mediated hemolysis are characteristic of cold AIHA. Sometimes, severe intravascular hemolysis occurs in cold AIHA. Two types of cold AIHA are cold agglutinin syndrome (CAS) and paroxysmal cold hemoglobinuria (PCH). A high titer of antibodies more than 1:64 in CAS may cause severe hemolysis, and a viral infection follows PCH.

In warm AIHA, 66% of our patients required a blood transfusion. Warm AIHA is characterized mainly by IgG, but sometimes, C3d may also be present. IgG causes extravascular hemolysis in the spleen, and the hemolysis rate is generally sustained. Most of the patients with warm AIHA are mostly stable with gradual daily loss of RBCs due to hemolysis. Sometimes, severe hemolysis with life-threatening anemia can occur if the complement is also associated with IgG.[7] Promising results are obtained when started on steroids patients of warm AIHA, and the rate of hemolysis is also controlled after the treatment. Transfusion support is less needed when hemolysis is controlled. In our study, warm AIHA patients needed less transfusion support than mixed and cold AIHA patients. Similar to our study, a single-center study done by Roumier et al. shows that around 65% of their warm AIHA patients needed a blood transfusion.[8] In female AIHA patients, 78% required transfusion, while 73% of male AIHA patients needed a transfusion. Transfusion support required by the females was little more than males (78% vs 73%) probably because in India females are generally anemic.

The transfusion requirements of most of our patients were limited to one unit. Transfusion support is essential until the patient improves clinically and Hb increases following medical treatment. Most of the patients improve little clinically after one transfusion, and they are started with steroids for further management. It is tough to get a compatible unit for AIHA patients because of autoantibodies in their serum. Just because of incompatibility, they should never be denied transfusion when they need the transfusion. Most of the clinicians might be unaware of the compatibility testing in AIHA, and they will be reluctant to accept the best match unit. All the clinicians should be educated, counseled, and encouraged to transfuse the best match unit during an emergency when there is a need for transfusion. The best match unit does not cause hemolysis, and there is a rise in Hb levels. A study done by Park et al. shows that transfusion of least incompatible units in AIHA patients is effective and safe, and there is a rise in Hb level posttransfusion without an increase in laboratory values of hemolysis.[3]

Many problems are faced during pretransfusion testing for AIHA patients. The majority of them will have blood group discrepancies. Some of them will be having alloantibody in addition to autoantibody, making pretransfusion testing even more difficult. It is mandatory to give an antigen-negative bag for that alloantibody. There is a high cross-match: transfusion ratio for these patients, and many units have to be crossed to get the best compatible unit. For all our AIHA patients, a minimum of six cross-matches had to be done to get the best match unit. Moreover, the TAT is always more, including all the immunohematology work up. Because of all this workup, there is a considerable delay between the transfusion request and the compatible unit. A study done by Das et al. shows that TAT was 222 min and even more when special techniques such as elution and adsorption were done.[9]

Because of difficulty in getting a compatible bag and increased TAT, which makes it even more challenging to get the transfusion during an emergency crisis, it is advisable to do phenotyping of these patients. Most AIHA patients need multiple transfusions because of relapse, treatment failure, and inconsistency with treatment. In general, before the first transfusion or if the previous transfusion is more than 3 months, then phenotyping of the patient can be done. It will be helpful in the future and further transfusion of the patient. We can give phenotype-matched blood to these patients. This is not routinely done in India. Rh Kell Phenotyped matched best match blood could be a better option in AIHA patients. Even today in India, we go for the best match unit without considering minor blood group phenotype match in these patients. Genotyping of the patient can also be done. However, it is costly, and many centers will not be able to afford it. The advantage of genotyping is it can be done in recently transfused patients. In a study done by Kenz et al. in seven patients where genotyping was done, it was highly effective and helpful, especially in pediatric patients.[10] However, it is done in fewer patients. Further studies are needed to be done in genotyping. Blood group phenotyping or genotyping beforehand may help in transfusing red cell antigen phenotype-matched blood.

One of the essential and sensitive tests to diagnose AIHA is the DCT. Various techniques are available to do DCT. The gold standard technique is the tube technique. Various advancements have occurred in immunohematology, and now there is a shift toward column agglutination technique because of increased sensitivity and ease to perform the test. In our study, all the tests were performed using gel technology by column agglutination technique other than blood grouping. Patients who had a higher grade of DCT more than +2 had severe hemolysis with increased laboratory parameters of indirect bilirubin, LDH, and decreased levels of Hb. Many of our patients were having severe hemolysis with indirect bilirubin of more than 1.5 mg/dl. Higher degree of hemolysis were observed in patients having DCT grade 4+. There was a direct correlation between increasing DCT grade and increasing indirect bilirubin with a significant P < 0.001. A similar finding was found in the study by Ray et al., which showed increasing DCT strength with in vivo hemolysis.[10] Regression analysis was done between DCT grade and indirect billirbin level and found to be statistically significant with P < 0.001, R2 = 22.3. Patients with LDH of more than 500 IU were having severe hemolysis. Totally 67 patients had LDH >500 IU, out of which 49 (73.13%) patients had a DCT Grade 4+. Although LDH was not clinically significant, P > 0.005 in our study, most patients with high DCT grades had increased LDH.

Patients with Hb <5 g/dl were having severe hemolysis and Hb more than 5 g/dl with moderate hemolysis. The mean Hb in our study was 5.1 g/dl. Forty-eight patients had Hb more than 5 g/dl. Sixty-four patients had <5 g/dl in that 53 (82.8%) patients had a DCT Grade 4+. Patients with a higher grade of DCT had low Hb, and it was clinically significant with P < 0.001. Regression analysis between the Hb level with the DCT grade, showed statistically significant with P < 0.001, R2 = 17.2. In our study, polyspecific AHG for both IgG and C3d was used. A study done by Wheeler et al.[12] shows that grade of DCT was directly related to in vivo hemolysis.[11] In the wheeler study, they used monospecific DCT for IgG and C3d, and both showed that DCT grade is correlated with in vivo hemolysis.

The decision to transfuse AIHA patients depends not only on Hb and laboratory values but also on many factors such as clinical condition, comorbidities, and patient's disease. Providing transfusion support to AIHA patients is sometimes very difficult, tedious, and time-consuming, and a lot of immunohematology workup is needed. Many of these patients will have blood group discrepancies, and finding a compatible unit for transfusion is doubtful. Unlike other patients, not all AIHA patients will have a compatible unit for transfusion. Transfusion should never be denied for an AIHA patient who needs transfusion because of incompatibility. If the need arises for transfusion, they can be transfused with the best match unit.

  Conclusion Top

The present study supports that the best-matched blood can be a life savior for AIHA patients in an emergency when none of the units are compatible. Our study results will add knowledge to current transfusion practices in AIHA patients; however, more studies from various centers may be needed to validate our findings.

Declaration of patient consent

Necessary consent has been obtained.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program 2018;2018:382-9.  Back to cited text no. 1
Shvidel L, Shtalrid M, Duek A, Haran M, Berrebi A, Sigler E. Direct antiglobulin test reactive with complement only in warm type autoimmune hemolytic anemia. Int J Lab Hematol 2008;30:494-8.  Back to cited text no. 2
Park SH, Choe WH, Kwon SW. Red blood cell transfusion in patients with autoantibodies: Is it effective and safe without increasing hemolysis risk? Ann Lab Med 2015;35:436-44.  Back to cited text no. 3
Mishra D, Sahoo D, Mahapatra S, Panigrahi A. Best-match blood transfusion in pediatric patients with mixed autoantibodies. Cancer Transl Med 2020;6:21-3.  Back to cited text no. 4
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Garratty G, Nance SJ. Correlation between in vivo hemolysis and the amount of red cell-bound IgG measured by flow cytometry. Transfusion 1990;30:617-21.  Back to cited text no. 5
Das SS, Chakrabarty R, Zaman RU. Immunohematological and clinical characterizations of mixed autoimmune hemolytic anemia. Asian J Transfus Sci 2018;12:99-104.  Back to cited text no. 6
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Naik R. Warm autoimmune hemolytic anemia. Hematol Oncol Clin North Am 2015;29:445-53.  Back to cited text no. 7
Roumier M, Loustau V, Guillaud C, Languille L, Mahevas M, Khellaf M, et al. Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single-center experience with 60 patients. Am J Hematol 2014;89:E150-5.  Back to cited text no. 8
Das SS, Zaman RU, Safi M. Incompatible blood transfusion: Challenging yet lifesaving in the management of acute severe autoimmune hemolytic anemia. Asian J Transfus Sci 2014;8:105-8.  Back to cited text no. 9
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El Kenz H, Efira A, Le PQ, Thiry C, Valsamis J, Azerad MA, et al. Transfusion support of autoimmune hemolytic anemia: how could the blood group genotyping help? Transl Res 2014;163:36-42.  Back to cited text no. 10
Ray GK, Mahapatra S, Mishra D, Parida P, Jena RK, Panigrahi R. Immunohematological workup, severity analysis and transfusion support in autoimmune hemolytic anemia patients. ISBT Sci Ser 2021;16:31-6.  Back to cited text no. 11
Wheeler CA, Calhoun L, Blackall DP. Warm reactive autoantibodies: Clinical and serologic correlations. Am J Clin Pathol 2004;122:680-5.  Back to cited text no. 12


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