American Journal of Medical Case Reports
ISSN (Print): 2374-2151 ISSN (Online): 2374-216X Website: Editor-in-chief: Samy, I. McFarlane
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American Journal of Medical Case Reports. 2021, 9(6), 328-330
DOI: 10.12691/ajmcr-9-6-6
Open AccessCase Report

Cold Agglutinin Hemolytic Anemia Induced by COVID-19

Amandeep S. Saini1, Kevin Shayani1 and Jacob Schwartz1,

1Lenox Hill Hospital, Department of Internal Medicine New York, NY, 10075

Pub. Date: March 18, 2021

Cite this paper:
Amandeep S. Saini, Kevin Shayani and Jacob Schwartz. Cold Agglutinin Hemolytic Anemia Induced by COVID-19. American Journal of Medical Case Reports. 2021; 9(6):328-330. doi: 10.12691/ajmcr-9-6-6


Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disorder characterized by the production of antibodies against red blood cell (RBC) antigens causing reduced circulation time. Diagnosis is based on clinical and laboratory signs of hemolysis and a positive direct antiglobulin test (DAT) after excluding alternative causes for those findings. AIHA is sub-classified according to auto-antibody, cold versus warm, and whether primary or secondary in nature. Warm AIHA is associated with the IgG antibody type and generally causes extravascular hemolysis in the spleen. Cold AIHA is less common, associated with the IgM antibody type, and leads to intravascular hemolysis after activating the classical complement pathway. Throughout the COVID-19 pandemic, it has been noted that hospitalized patients are in a pro-inflammatory state (e.g. elevated D-dimer, ferritin, C-reactive protein) that predisposes them to hematological complications such as venous thromboembolisms (VTE). Although the exact pathophysiology remains unclear, evidence points towards fatal cytokine release. Moreover, there have been case reports of AIHA in a subset of COVID-19 patients and researchers postulate molecular mimicry amongst the epitopes of Ankyrin 1 and viral spike protein as a potential culprit. This case report discusses an elderly patient with multiple co-morbidities who was admitted for acute hypoxemic respiratory failure from COVID-19 and found to have cold agglutinin hemolytic anemia. We are looking to contribute to the current understanding of AIHA as a complication of COVID-19 infection.

coronavirus COVID-19 AIHA anemia hemolysis DAT Coombs test

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[1]  John Hopkins Coronavirus Resource Center. (n.d.). Global Cases. Johns Hopkins University & Medicine. Retrieved January 13, 2021, from
[2]  Jacobs J, Eichbaum Q. COVID-19 associated with severe autoimmune hemolytic anemia. Transfusion. 2020; 1-6.
[3]  Lazarian G, Quinquenel A, Bellal M, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol. 2020; 190(1): 29-31.
[4]  Hindilerden F, Yonal-Hindilerden I, Akar E, Yesilbag Z, Kart-Yasar K. Severe Autoimmune Hemolytic Anemia in COVID-19 ─░nfection, Safely Treated with Steroids. Mediterr J Hematol Infect Dis. 2020; 12(1): e2020053.
[5]  Bass, G. F., Tuscano, E. T., & Tuscano, J. M. (2014). Diagnosis and classification of autoimmune hemolytic anemia. Autoimmunity Reviews. 2013; 13(4-5): 560-564.
[6]  Campos-Cabrera G, Mendez-Garcia E, Mora-Torres M, et al. Autoimmune Hemolytic Anemia As Initial Presentation of COVID-19 Infection. Blood. 2020; 136(1): 8.
[7]  Maslov DV, Simenson V, Jain S, Badari A. COVID-19 and Cold Agglutinin Hemolytic Anemia. TH Open. 2020; 4(3): e175-e177.
[8]  Patil NR, Herc ES, Girgis M. Cold agglutinin disease and autoimmune hemolytic anemia with pulmonary embolism as a presentation of COVID-19 infection. Hematol Oncol Stem Cell Ther. 2020; S1658-3876(20)30116-3.
[9]  Engelfriet CP, Borne AE, Beckers D, Van Loghem JJ. Autoimmune haemolytic anaemia: serological and immunochemical characteristics of the autoantibodies; mechanisms of cell destruction. Ser Haematol. 1974; 7(3): 328-347.
[10]  Hill QA, Stamps R, Massey E, et al. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017; 176(3): 395-411.