A patient with cold agglutinin disease (CAD) tested negative on the Coomb’s test, as published in a case study in the Asian Journal of Transfusion Science.

However, autoagglutination tests using the patient’s own red blood cells (RBCs) mixed with the patient’s serum did react at 4°C. Blood samples from the patient also displayed visible clumping to the naked eye which disappeared when the sample was heated but reappeared when it was refrigerated.

The patient’s serum had a slight pink color as well, indicating hemoglobinemia. Blood tests revealed that lactate dehydrogenase levels were elevated and unconjugated bilirubin levels were also mildly raised.

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A shift to the left in the neutrophil series was observed on peripheral blood smear along with signs of sepsis, such as toxic granulation. Large clumps of RBCs, as well as increased levels of nucleated RBCs and polychromatophilic cells, were also seen on the smears.

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Bilateral interstitial infiltrates were observed on the chest X-ray as well, which were indicative of atypical pneumonia. The patient was ultimately diagnosed with CAD in conjunction with atypical pneumonia, alcohol withdrawal syndrome, and chronic obstructive pulmonary disease (COPD).

The reason for the negative Coomb’s test in the case study is not known since further testing was not available due to cost factors, but the authors suggested some possible reasons why.

“[The cause of negative Coomb’s] can be due to technical fallacies of inadequate cell washing or delay in addition of reagent or it may be due to severe hemolysis where coated RBCs are cleared rapidly, or in rare cases, they may be due to IgA-type autoantibodies which may not be picked up in the routine tests,” they said.

The patient in the case study was a 54-year-old male who had a history of chronic alcoholism and COPD. The initial presentation included a delirious state and the patient was admitted for alcohol withdrawal syndrome.

The patient developed hypotension, hypoxemia, a high-grade fever, and a continuous cough after admission. After a diagnosis of sepsis with type 2 respiratory failure, he was moved to the intensive care unit where he received further blood work that revealed the CAD. 


Balraam KVV, Masood A, Garg N, Somasundaram V. Coomb’s negative cold agglutinin disease: a rare report of an incidentally detected case. Asian J Transfus Sci. 2021;15(2):233-236. doi:10.4103/ajts.AJTS_78_20