Clinical Biochemistry 48 (2015) 463–464
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Letter to the Editor Hemoglobin C in a patient with sickle cell anemia: Transfusion-acquired SC disease Keywords: Hemoglobinopathy Sickle cell anemia SC disease Hemoglobin C Red cell exchange transfusion
Hemoglobin variants are relatively common, with over 700 new cases identified in Northern Alberta in 2013 [1]. While most are clinically silent, some have adverse hematological and physiological consequences. In particular, homozygous HbS disease (sickle cell anemia) may cause sickling, hypoxia under stress, episodic abdominal or skeletal pain, and spleen enlargement. Similar, but less severe symptoms are observed in hemoglobin SC disease. Red cell exchange transfusion is a well-recognized treatment for patients with sickle cell anemia and SC disease. In Northern Alberta, samples are collected before and after red cell exchange for quantification of HbA, HbS, HbF and HbA2 by HPLC in order to monitor and guide treatment.
Hemoglobin fractionation was requested by a hematologist. HPLC analysis was performed using the β-thalassemia Short Program on the BioRad Variant II. The manufacturer's reagents and calibrators were employed. Results revealed the presence of HbA, and small percentages of two hemoglobin variants in the HbS and HbC windows (Fig. 1A). At first glance, this pattern is suggestive of SC disease with recent transfusion. However, the percentages of HbS and C are typically quite similar in SC disease, whereas the percentage of HbS (14%) was more than double that of HbC (6%) in this case. Review of the patient's history indicated that the sample in question was in fact a post-transfusion specimen. However, the patient had a previous diagnosis of sickle cell anemia, not SC disease. The pre-transfusion sample contained 47% HbS, but no other variant was noted (Fig. 1B). Electrophoresis at acid and alkaline pH confirmed the presence of the additional variant in the post-transfusion sample, showing a migration pattern consistent with HbC. We hypothesized that the patient was transfused with red cells containing HbC. To investigate this possibility, we obtained anonymized donor segments from the transfused units. These are aliquots of the transfused red cells that are retained for at least 7 days post transfusion to allow investigation of transfusion reactions and other transfusion related events. Each specimen was diluted 1:300 with BioRad wash/
Fig. 1. Hemoglobin fractionation reveals a hemoglobin variant in the post-transfusion specimen that is absent from the pre-transfusion sample. HPLC profile using the BioRad Variant II βthalassemia Short Program. (A) Post-transfusion specimen; (B) pre-transfusion specimen.
http://dx.doi.org/10.1016/j.clinbiochem.2015.01.013 0009-9120/© 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
464
Letter to the Editor
Table 1 Patient's hemoglobin C and S percentages over time. Pre = pre-transfusion, post = posttransfusion. Day 1
% HbS % HbC
Day 58
Pre
Post
Pre
Post
47.4 0.0
13.7 5.8
47.1 2.8
13.9 0.8
diluent solution and hemoglobin fractionation was performed. One of the 7 donor segments showed an HPLC pattern consistent with HbC trait, which was confirmed by electrophoresis. Consistent with these results, the patient's HbC decreased over time with kinetics reflecting red cell turnover (Table 1), whereas HbS increased in a manner expected for sickle cell anemia. This study complied with the institutional ethics requirements, and the findings were communicated to Canadian Blood Services. The donor was notified regarding the presence of a clinically insignificant hemoglobin variant and advised to seek medical follow-up. Most blood donors who are heterozygous for a hemoglobin variant are asymptomatic, so there is no reason to exclude them from the donor pool. Canadian standards require that donor units intended for exchange transfusion in neonates be screened and found negative for HbS [2]. However, no such requirement exists for other hemoglobin variants or other types of transfusion, including adult red cell exchange. As a result, transfusion-acquired hemoglobinopathies are a real possibility. Despite this, only a few cases have been documented, both in patients with sickle cell anemia [3,4] and those transfused for other ailments [5,6]. The acquisition of HbC by red cell exchange was not clinically significant in this case, as it only accounted for 6% of the patient's hemoglobin. However, transfusion-acquired hemoglobinopathies may pose a diagnostic dilemma, especially if the laboratory and/or ordering physician are unaware of the transfusion history. This may cause misdiagnosis and unnecessary follow-up testing and counseling. Consequently, both laboratorians and physicians should be aware of this unique preanalytical error.
References [1] Higgins T, Rodriguez Capote K. Distribution of hemoglobinopathies and thalessemias in a Northern Alberta population. Clin Chem 2014;60(S10):A-300. [2] CAN/CSA-Z902-10. Blood and blood components (Standard 10.9.1.9). 2nd ed. Canadian Standards Association; 2010. [3] 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 Dec;130(12):1830–3. [4] Saidenberg E, Freedman M, Fournier E, Lesley P, Goldman M. Transfusion Med Illustrated: hemoglobin C acquired through exchange transfusion. Transfusion Mar 2012;52(3):466. [5] Rechavi G, Brok-Simoni F, Ben-Bassat I, Ramot B. Spurious haemoglobinopathy. Lancet May 3 1986;1(8488):1035. [6] Suarez AA, Polski JM, Grossman BJ, Johnston MF. Blood transfusion-acquired hemoglobin C. Arch Pathol Lab Med Jul 1999;123(7):642–3.
Mathew P. Estey⁎ Karina Rodriguez Capote Vilte E. Barakauskas DynaLIFEDx, Canada Department of Laboratory Medicine and Pathology, University of Alberta, Canada ⁎Corresponding author at: DynaLIFEDx, #200, 10150-102 Street, Edmonton, Alberta T5J 5E2, Canada. E-mail address: [email protected] (M.P. Estey). Gwen Clarke Department of Laboratory Medicine and Pathology, University of Alberta, Canada Canadian Blood Services, Edmonton, Canada Trefor Higgins DynaLIFEDx, Canada 24 December 2014
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Letter to the Editor Hemoglobin C in a patient with sickle cell anemia: Transfusion-acquired SC disease Keywords: Hemoglobinopathy Sickle cell anemia SC disease Hemoglobin C Red cell exchange transfusion
Hemoglobin variants are relatively common, with over 700 new cases identified in Northern Alberta in 2013 [1]. While most are clinically silent, some have adverse hematological and physiological consequences. In particular, homozygous HbS disease (sickle cell anemia) may cause sickling, hypoxia under stress, episodic abdominal or skeletal pain, and spleen enlargement. Similar, but less severe symptoms are observed in hemoglobin SC disease. Red cell exchange transfusion is a well-recognized treatment for patients with sickle cell anemia and SC disease. In Northern Alberta, samples are collected before and after red cell exchange for quantification of HbA, HbS, HbF and HbA2 by HPLC in order to monitor and guide treatment.
Hemoglobin fractionation was requested by a hematologist. HPLC analysis was performed using the β-thalassemia Short Program on the BioRad Variant II. The manufacturer's reagents and calibrators were employed. Results revealed the presence of HbA, and small percentages of two hemoglobin variants in the HbS and HbC windows (Fig. 1A). At first glance, this pattern is suggestive of SC disease with recent transfusion. However, the percentages of HbS and C are typically quite similar in SC disease, whereas the percentage of HbS (14%) was more than double that of HbC (6%) in this case. Review of the patient's history indicated that the sample in question was in fact a post-transfusion specimen. However, the patient had a previous diagnosis of sickle cell anemia, not SC disease. The pre-transfusion sample contained 47% HbS, but no other variant was noted (Fig. 1B). Electrophoresis at acid and alkaline pH confirmed the presence of the additional variant in the post-transfusion sample, showing a migration pattern consistent with HbC. We hypothesized that the patient was transfused with red cells containing HbC. To investigate this possibility, we obtained anonymized donor segments from the transfused units. These are aliquots of the transfused red cells that are retained for at least 7 days post transfusion to allow investigation of transfusion reactions and other transfusion related events. Each specimen was diluted 1:300 with BioRad wash/
Fig. 1. Hemoglobin fractionation reveals a hemoglobin variant in the post-transfusion specimen that is absent from the pre-transfusion sample. HPLC profile using the BioRad Variant II βthalassemia Short Program. (A) Post-transfusion specimen; (B) pre-transfusion specimen.
http://dx.doi.org/10.1016/j.clinbiochem.2015.01.013 0009-9120/© 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
464
Letter to the Editor
Table 1 Patient's hemoglobin C and S percentages over time. Pre = pre-transfusion, post = posttransfusion. Day 1
% HbS % HbC
Day 58
Pre
Post
Pre
Post
47.4 0.0
13.7 5.8
47.1 2.8
13.9 0.8
diluent solution and hemoglobin fractionation was performed. One of the 7 donor segments showed an HPLC pattern consistent with HbC trait, which was confirmed by electrophoresis. Consistent with these results, the patient's HbC decreased over time with kinetics reflecting red cell turnover (Table 1), whereas HbS increased in a manner expected for sickle cell anemia. This study complied with the institutional ethics requirements, and the findings were communicated to Canadian Blood Services. The donor was notified regarding the presence of a clinically insignificant hemoglobin variant and advised to seek medical follow-up. Most blood donors who are heterozygous for a hemoglobin variant are asymptomatic, so there is no reason to exclude them from the donor pool. Canadian standards require that donor units intended for exchange transfusion in neonates be screened and found negative for HbS [2]. However, no such requirement exists for other hemoglobin variants or other types of transfusion, including adult red cell exchange. As a result, transfusion-acquired hemoglobinopathies are a real possibility. Despite this, only a few cases have been documented, both in patients with sickle cell anemia [3,4] and those transfused for other ailments [5,6]. The acquisition of HbC by red cell exchange was not clinically significant in this case, as it only accounted for 6% of the patient's hemoglobin. However, transfusion-acquired hemoglobinopathies may pose a diagnostic dilemma, especially if the laboratory and/or ordering physician are unaware of the transfusion history. This may cause misdiagnosis and unnecessary follow-up testing and counseling. Consequently, both laboratorians and physicians should be aware of this unique preanalytical error.
References [1] Higgins T, Rodriguez Capote K. Distribution of hemoglobinopathies and thalessemias in a Northern Alberta population. Clin Chem 2014;60(S10):A-300. [2] CAN/CSA-Z902-10. Blood and blood components (Standard 10.9.1.9). 2nd ed. Canadian Standards Association; 2010. [3] 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 Dec;130(12):1830–3. [4] Saidenberg E, Freedman M, Fournier E, Lesley P, Goldman M. Transfusion Med Illustrated: hemoglobin C acquired through exchange transfusion. Transfusion Mar 2012;52(3):466. [5] Rechavi G, Brok-Simoni F, Ben-Bassat I, Ramot B. Spurious haemoglobinopathy. Lancet May 3 1986;1(8488):1035. [6] Suarez AA, Polski JM, Grossman BJ, Johnston MF. Blood transfusion-acquired hemoglobin C. Arch Pathol Lab Med Jul 1999;123(7):642–3.
Mathew P. Estey⁎ Karina Rodriguez Capote Vilte E. Barakauskas DynaLIFEDx, Canada Department of Laboratory Medicine and Pathology, University of Alberta, Canada ⁎Corresponding author at: DynaLIFEDx, #200, 10150-102 Street, Edmonton, Alberta T5J 5E2, Canada. E-mail address: [email protected] (M.P. Estey). Gwen Clarke Department of Laboratory Medicine and Pathology, University of Alberta, Canada Canadian Blood Services, Edmonton, Canada Trefor Higgins DynaLIFEDx, Canada 24 December 2014
