Cold-Reactive Erythrocyte Agglutination Causing Analytical Interference in Automated Hematology: A Case Report

A Case Report

Authors

  • Riana Retno Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jawa Timur, Surabaya, 60294, Indonesia
  • Shobran Naufal Universitas Hang Tuah Surabaya

DOI:

https://doi.org/10.33005/jdiversemedres.v3i8.369

Keywords:

cold-reactive erythrocyte agglutination, peripheral blood smear, specimen warming

Abstract

Cold-reactive erythrocyte agglutination is an important cause of analytical interference in automated hematology testing. We report a 55-year-old man with severe anemia, leukocytosis, thrombocytopenia, and suspected hematologic malignancy in whom hematological parameters changed substantially following specimen warming. The blood specimen had a sandy appearance and was incubated at 37°C before repeat analysis. Before incubation, WBC was 32,270/µL, RBC 0.29 × 10⁶/µL, hemoglobin 8.3 g/dL, hematocrit 2.8%, MCH 283.3 pg, and MCHC 295.8 g/dL. Following incubation, WBC was 19,630/µL, RBC 1.93 × 10⁶/µL, hemoglobin 6.1 g/dL, hematocrit 17.8%, MCH 31.7 pg, and MCHC 34.3 g/dL. Peripheral blood smear demonstrated erythrocyte agglutination and approximately 10% immature cells resembling myeloid blasts. This case highlights the importance of recognizing cold-reactive erythrocyte agglutination, appropriate specimen warming, and peripheral blood smear examination to improve interpretation of automated hematology results.

Downloads

Download data is not yet available.

References

Berentsen S. New insights in the pathogenesis and therapy of cold agglutinin-mediated autoimmune hemolytic anemia. Front Immunol. 2020;11:590.

Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the First International Consensus Meeting. Blood Rev. 2020;41:100648.

Berentsen S, Barcellini W, D'Sa S, Randen U, Tvedt THA, Fattizzo B, et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood. 2020;136(4):480-488.

Gertz MA. Updates on the diagnosis and management of cold autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2022;36(2):341-352.

Zahid H, Hadef R, Labrini F, Yahyaoui A, Messaoudi N. Cold agglutinins revealed by abnormalities to the cell blood count: a case report. Pan Afr Med J. 2021;38:328.

Berentsen S. How I treat cold agglutinin disease. Blood. 2021;137(10):1295-1303.

Gabbard AP, Booth GS. Cold agglutinin disease. Clin Hematol Int. 2020;2(3):95-100.

Xie, H., Lv, S., Su, W. and Xu, W. Effect of preheating at 40℃ for 15 minutes to high-titer cold agglutinins on complete blood count. Int J Lab Hematol. 2021;43: e271-e275.

Yang Y, Wang Q, Lu M. Impact of Severe Cold Agglutination on Routine Red Blood Cell Parameters and Correction Strategies. Clin Lab. 2026;72(5).

Falvella FS, Chibireva M, Panteghini M. Prospective validation of an automatic reflex test for identifying spurious elevations of mean corpuscular haemoglobin concentration due to the presence of cold agglutinins. Scand J Clin Lab Invest. 2021;81(7):598-600.

Rocca Forte V, et al. Use of the reticulocyte channel warmed to 41°C of the XN-9000 analyzer in samples with the presence of cold agglutinins. Hematol Transfus Cell Ther. 2021;43(2):147-155.

Berentsen S. Cold-antibody autoimmune hemolytic anemia: its association with neoplastic disease and impact on therapy. Curr Oncol Rep. 2024;26(9):1085-1096.

Guenther A, Tierens A, Malecka A, Delabie J. The histopathology of cold agglutinin disease-associated B-cell lymphoproliferative disease. Am J Clin Pathol. 2023;160(3):229-237.

Michel M, Crickx E, Fattizzo B, Barcellini W. Autoimmune haemolytic anaemias. Nat Rev Dis Primers. 2024;10(1):82.

Downloads

Published

2026-08-30

How to Cite

Retno, R., & Naufal, S. (2026). Cold-Reactive Erythrocyte Agglutination Causing Analytical Interference in Automated Hematology: A Case Report: A Case Report. Journal of Diverse Medical Research : Medicosphere, 3(8), 407–417. https://doi.org/10.33005/jdiversemedres.v3i8.369