Infection with Babesia microti may promote the development of both cold antibody-mediated autoimmune hemolytic anemia (AIHA) such as cold agglutinin disease (CAD) and warm antibody-mediated AIHA, according to an article published in the British Journal of Haematology.

The study authors compiled a literature review of all reported cases of babesiosis-associated AIHA and presented a novel case report of babesiosis-associated CAD.

They reviewed PubMed and EMBASE databases from inception to January 12, 2023. A total of 20 reported cases of babesiosis-associated warm antibody-mediated AIHA were identified, describing 12 male and 8 female patients.

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Seven patients were diagnosed with AIHA concurrently with active B microti infection, while in 10 patients the diagnosis was established up to 4 weeks after the infection. Moreover, 6 patients had a history of conditions associated with a predisposition to developing AIHA. Spleen presence/absence was reported in 17 patients, and 100% had their spleen removed.

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Among the 20 patients, 10 had a direct antiglobulin test (DAT) positive for both IgG and C3, 9 were positive for IgG, and 1 had a negative DAT but the presence of a warm autoantibody with anti-Jka specificity in the eluate.

The review showed that 9 patients were treated with at least 1 red blood cell (RBC) transfusion, with 4 patients receiving at least 1 RBC transfusion and/or plasma exchange. The majority of patients received azithromycin and atovaquone and 9 received additional immunosuppressive therapy. One patient died due to multiorgan failure.

In addition, the study authors described the case of a 63-year-old female patient with presumptive cold antibody-mediated AIHA. The patient presented to an outside hospital with fever, chills, anemia, and a history of a tick bite one month prior. She also reported a significant history of metastatic ovarian cancer 18 years earlier.

After the infection with B microti was confirmed, the patient was started on atovaquone and azithromycin. Three days after discharge, the evaluation revealed decreased parasitemia and worsening anemia. The patient received 2 units of RBCs and was transferred to a different facility.

Due to hemolysis evidenced by abnormal chemical studies, intermittent borderline-detectable parasitemia, and down-trending hemoglobin, the patient received another single RBC transfusion. DAT via standard tube testing was positive with anti-IgG, -C3d polyspecific, and anti-C3 monospecific reagents, but negative using anti-IgG monospecific reagents.

The patient was discharged 2 days later after her clinical condition improved. She still received azithromycin, atovaquone, and folic acid.

Five days after the first testing, DAT was positive for C3 and negative for IgG. The cold agglutinin titers at 4°C using type O RhD-positive donor RBCs via standard tube methods without potentiating agents were 1:256, while the titer was less than 1:32 a week prior.

“In patients with hemolysis that appears out of proportion to the parasitemia, assessment with DAT and elution studies may be informative. Importantly, if the DAT is positive for C3 and negative for IgG, further analysis of cold agglutinins may be warranted, particularly since treatment (if needed) for this entity generally differs as compared with warm autoantibody disease,” Jacobs and colleagues concluded.


Jacobs JW, Binns TC, Abels E, Tormey CA. Autoimmune haemolytic anaemia secondary to babesiosis: a review of reported cases and description of a novel association with cold antibody-mediated haemolytic anaemia. Br J Haematol. Published online February 20, 2023. doi:10.1111/bjh.18710