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Case Reports
. 2025 May 26;17(5):e84833.
doi: 10.7759/cureus.84833. eCollection 2025 May.

Cold Agglutinin Autoimmune Hemolytic Anemia Revealing Undiagnosed Diffuse Large B-cell Lymphoma Following COVID-19 Vaccination

Faiza Humayun Khan  1 , Ahsan Ayaz  1 , Tamer Zahdeh  1
Affiliations
Case Reports

Cold Agglutinin Autoimmune Hemolytic Anemia Revealing Undiagnosed Diffuse Large B-cell Lymphoma Following COVID-19 Vaccination

Faiza Humayun Khan et al. Cureus. .

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma that can be associated with autoimmune hemolytic anemia (AIHA), including the rare cold agglutinin hemolytic anemia (CAHA) subtype. Emerging reports have also suggested a potential link between COVID-19 vaccination and the development of AIHA. We report a case of a 56-year-old male with a history of autoimmune diseases who developed symptomatic hemolytic anemia shortly after receiving an mRNA COVID-19 booster. Laboratory evaluation revealed hemolysis with a positive direct antiglobulin test for C3 and negative for IgG, consistent with CAHA. Imaging demonstrated hepatosplenomegaly and isolated lymphadenopathy, and subsequent biopsies confirmed the diagnosis of DLBCL. Although initiated on steroids for presumed autoimmune hemolysis, the patient's limited response further supported CAHA secondary to underlying lymphoma. While COVID-19 vaccines are widely recognized as safe and effective, rare cases of post-vaccination AIHA have been reported. In this case, it remains unclear whether the CAHA was directly triggered by vaccination, unmasked by underlying DLBCL, or a coincidental occurrence. The temporal association observed highlights the complex interplay between immune activation, vaccination, and hematologic malignancy. This case underscores the importance of maintaining a broad differential diagnosis when evaluating hemolytic anemia following vaccination, particularly in patients with autoimmune backgrounds, and highlights the need for further research to better understand potential immunologic interactions among COVID-19 vaccination, AIHA, and occult lymphoma.

Keywords: auto-immune hemolytic anemia; autoimmune disease; cold agglutunin hemolytic anemia; covid 19 vaccination; diffuse large b cell lymphoma (dlbcl).

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Conflict of interest statement

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Computed tomography (CT) of the abdomen demonstrating hepatosplenomegaly and marked porta hepatis lymphadenopathy (arrow).
See this image and copyright information in PMC

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