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CASE REPORT  
Year : 2011  |  Volume : 54  |  Issue : 3  |  Page : 609-611
Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major


Department of Haematology, IRCH Building, 1st Floor, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

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Date of Web Publication20-Sep-2011
 

   Abstract 

Apparent hemoglobinopathy acquired after blood transfusion is an uncommon cause of diagnostic dilemma resulting in repeated testing and delay in the diagnosis. Out of the 1530 hemoglobin (Hb)- high-performance liquid chromatography (HPLC) performed at our hospital (May 2009 to April 2010), 3 pediatric cases of thalassemia major were detected having posttransfusion hemoglobinopathy with HbS ranging from 9.9% to 18.5%. In all three cases, there was no variant hemoglobin in earlier documented Hb-HPLC. It is important to be aware of and consider apparent transfusion-induced hemoglobinopathy in patients with unusual percentage of variant hemoglobin to avoid unnecessary treatment and counseling.

Keywords: HbS, hemoglobinopathy, thalassemia major, transfusion

How to cite this article:
Gupta SK, Sharma M, Tyagi S, Pati HP. Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major. Indian J Pathol Microbiol 2011;54:609-11

How to cite this URL:
Gupta SK, Sharma M, Tyagi S, Pati HP. Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Nov 29];54:609-11. Available from: https://www.ijpmonline.org/text.asp?2011/54/3/609/85112



   Introduction Top


Transfusion-induced hemoglobinopathy may be defined as the transfusion of a unit of non-AA blood leading to the consideration of an alternative hemoglobin (Hb) variant in the recipient. [1] This may result in repeated testing causing delay in the diagnosis and increasing the overall cost of analysis. Rarely, the complications related to the variant Hb, e.g., HbS, have also occurred in the recipients. At our hospital, 1530 Hb)-high- performance liquid chromatography (HPLC) analyses were performed from May 2009 to April 2010, using Bio-Rad VARIANT II and the corresponding Beta-Thalassemia Short Program, (Bio-Rad Laboratories, Inc., Hercules, CA, USA). We detected three unusual cases of thalassemia major aged 1.5-3 years, who presented with a variant hemoglobin peak of HbS on Hb-HPLC.


   Case Report Top


The first case was a 2-year-old male with thalassemia major with Hb-HPLC revealing a peak of 18.5% in the "sickle (S)-window," with a retention time (RT) of 4.36 min, creating a diagnostic dilemma. There was a slow-moving band in the HbS region on alkaline Hb electrophoresis. Both parents were heterozygous and the patient was homozygous for IVS 1-5 mutation on amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). On examining old records, it was noted that his Hb-HPLC done 1 year back did not show any HbS. The patient was a resident of Orissa, a state with a higher prevalence of sickle cell disorders and had received transfusion recently in a local hospital, possibly from a sickle trait donor.

The second case was a 1.5-year-old male with thalassemia major having a peak of 18.2% (RT 4.38 min) in the S-window and the third patient was a 3-year-old thalassemia major female with a peak of 9.9% (RT 4.29 min; [Figure 1]) in the S-window on Hb-HPLC, confirmed on Hb electrophoresis. In both these cases, there was a history of recent transfusion, absence of a variant hemoglobin on Hb-HPLC done at a younger age and the parents in both the cases were thalassemia carriers, which confirmed transfusion-induced hemoglobinopathy. The details of Hb-HPLC and hemogram findings of these cases and their parents have been provided in [Table 1].
Table 1: Hb-HPLC and hemogram details of the patients and their parents

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Figure 1: Hemoglobin chromatogram showing a peak of 9.9% in the S-window (RT 4.29 min) in case 3. The other peaks are HbF (5.5%), HbA (70.2%) and HbA2 (2.6%; X-axis: time in minutes; Y-axis: % hemoglobin)

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   Discussion Top


In a sickle cell trait patient, the expected HbS is around 40% and >50% in homozygous SS and double heterozygotes. Extremely low levels of HbS are unusual in sickle cell patients but can be encountered with coexistent alpha-thalassemia or when suppression of the synthesis of HbS occurs in chronically transfused patients. [2],[3],[4] Rarely, very low HbS (11.4%) has been reported in a patient with beta-thalassemia mutation in cis (on same allele) of a sickle cell gene. [5] Other differential diagnosis in cases with low levels of HbS are carry-over from the previous sample, hemoglobin C1c (glycated form of hemoglobin C), unstable alpha or even delta chain variants, e.g., A2' (A2-prime) which co-elute in the "S-window" on Hb-HPLC.

The occurrence of unusual percentages of variant hemoglobins after transfusion creates a diagnostic challenge as it becomes difficult to differentiate this condition from the dilutional effects of transfusion on the variant hemoglobin in the recipient. Apparent transfusion-induced hemoglobinopathies can be diagnosed with certainty by the identification of that variant hemoglobin in the transfused red blood cell units. However, when it is not possible, a strong evidence for the same can be obtained if the abnormal hemoglobin decreases and/or disappears with time, or was not present in previous results. Family studies also help in ruling out a true hemoglobinopathy in such cases. In all our cases, there was no variant hemoglobin in earlier analysis of patients as well as their parents. The reduction of variant hemoglobin could not be documented due to the lack of follow-up in these cases. The reason for frequent finding of such cases at our hospital may be the referral of thalassemia major patients for stem cell transplantation. Many of these patients have a history of chronic transfusion at peripheral centers without any provision for donor screening for the sickle cell trait.

The percentage of the HbS in the transfusion-induced hemoglobinopathy recipients ranged from 1.4% to 7.1% in four reported cases in a previous series. [1] Our cases have shown HbS ranging from 9.9% to 18.5%. The reason for higher HbS values in our patients may be related to the reduced gap between the transfusion and Hb-HPLC testing as well as the young age of the recipients. The higher HbS levels in the transfused pediatric patients increases the risk of sickling complications more as compared to the adult recipients. This is true especially in neonates, in whom multiple renal and splenic infarcts following transfusion with sickle trait blood has been reported earlier. [6] Transfused HbS may also create complications during anesthesia in these patients. However, no complications were seen due to transfused HbS in any of our patients. Blood from sickle trait donors can also lead to blockage of leukodepletion filters. [7] In the absence of a routine newborn screening program or screening before blood donation, many donors are not aware that they are carriers of a hemoglobinopathy.

With these cases, we want to highlight that transfusion-induced hemoglobinopathy should be considered in the differential diagnosis of patients having unusually low levels of the variant hemoglobin, especially if recently transfused in endemic areas with a higher prevalence of hemoglobinopathies. Repeat testing of a patient after some time, parental study, and a review of previous records help to resolve these cases. Patients receiving regular transfusion may get different Hb variants (e.g., Hb E, C, O-Arab, etc.) or transient recurrence of a variant over a period of time. Thus, it is important to maintain all records for proper interpretation and avoid Hb-HPLC testing in the immediate posttransfusion period.


   Acknowledgment Top


We thank Mr. Nawal Prakash, Laboratory Technologist, Department of Haematology, AIIMS, for the laboratory assistance.

 
   References Top

1.Kozarski TB, Howanitz PJ, Howanitz JH, Lilic N, Chauhan YS. Blood Transfusions Leading to Apparent Hemoglobin C, S, and O-Arab Hemoglobinopathies. Arch Pathol Lab Med 2006;130:1830-3.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Head CE, Conroy M, Jarvis M, Phelan L, Bain BJ. Some observations on the measurement of haemoglobin A2 and S percentages by high performance liquid chromatography in the presence and absence of thalassaemia. J Clin Pathol 2004;57:276-80.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Zinkham WH, Seidler AJ, Kickler TS. Variable degree of suppression of hemoglobin S synthesis in subjects with hemoglobin SS disease on a long-term transfusion regimen. J Pediatr 1994;124:215-9.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Scurlock D, Risin SA. Pathologic quiz case : A0 16-year-old adolescent girl with a trace level of hemoglobin s detected by high-performance liquid chromatography. Almost complete suppression of hemoglobin S in a sickle cell disease patient undergoing long-term transfusion therapy. Arch Pathol Lab Med 2005;129 : 0 e107-8.  Back to cited text no. 4
    
5.Baklouti F, Ouazana R, Gonnet C, Lapillonne A, Delaunay J, Godet J. b+-Thalassemia in cis of a sickle cell gene : O0 ccurrence of a promoter mutation on a bS chromosome. Blood 1989;74:1817-22.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Novak RW, Brown RE. Multiple Renal and Splenic Infarctions in a Neonate Following Transfusion with Sickle Trait Blood. Clin Pediatr (Phila) 1982;21:239-41.  Back to cited text no. 6
[PUBMED]    
7.Beard MJ, Cardigan R, Seghatchian J, Krailadsiri P, Williamson LM. Variables determining blockage of WBC-depleting filters by Hb sickle cell trait donations. Transfusion 2004;44:422-30.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  

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Correspondence Address:
Sanjeev K Gupta
B-1/226, Yamuna Vihar, Delhi - 110 053
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.85112

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    Figures

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