A case of simultaneous onset of coronavirus disease 2019 (COVID-19), warm autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) was recently reported in Cureus.

The 51-year-old male patient was found to be positive for COVID-19 via reverse polymerase chain reaction testing while being positive for immunoglobulin (Ig) G and C3 complement antibodies (indicators of warm AIHA) on a direct antiglobulin test (DAT). A review by a hematopathologist also uncovered agglutination on immediate spin reactivity testing, consistent with CAD.

“In immediate spin testing, the patient’s plasma and donor red cells are spun without the addition of antiglobulin. IgG is not large enough to agglutinate on a rapid spin. This indicates that a precipitate without additives below physiologic temp is diagnostic of IgM disease such as cold AIHA. Our institution uses immediate spin reactivity as a cold agglutinin screen,” the authors explained.

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They added, “To our knowledge, this is the first case of both warm and cold AIHA presenting simultaneously in COVID-19 infection. Unlike most cases in the existing literature, this patient had no history of underlying hematologic malignancy and both warm and cold AIHA [CAD].”

The patient presented with jaundice, fatigue, elevated lactate dehydrogenase, severe anemia, and decreased haptoglobin. The patient also had thrombocytopenia, with the lowest platelet count of 65 thousand cells/mL recorded on the sixth day of hospitalization. The cause of the thrombocytopenia was unclear, but the authors attributed it to either COVID-19 infection or associated immune thrombocytopenia purpura (ITP) because ITP has been shown to be associated with viral infections and tests for heparin-induced thrombocytopenia were negative.

Computed tomography (CT) scans of the chest on hospital day 3 revealed pulmonary emboli in all lobes, which were mostly nonocclusive with a moderate clot burden. For treatment, the patient was started on apixaban.

The patient was administered 4 units of packed red blood cells on the day of hospital admission, with a fifth unit given on day 2. On day 2 he was also started on 1 mg/kg (100 mg daily) of prednisone for the treatment of AIHA. The patient was discharged on day 8 and continued 100 mg daily prednisone for 2 weeks.

At the 2-week follow-up, the hemolysis lab results had normalized. The dose of prednisone was reduced to 80 mg daily at the 1-month follow-up and 60 mg at the 2-month follow-up. At 70 days after discharge, DAT remained positive for IgG and C3 and prednisone was reduced to 50 mg daily.


Brazel D, Eid T, Harding C. Warm and cold autoimmune hemolytic anemia in the setting of COVID-19 disease. Cureus. 2021;13(9):e18127. doi:10.7759/cureus.18127