Researchers authored a case report of a 69-year-old man with chest pain who was diagnosed with cold agglutinin disease (CAD), published in the Medical Journal of Malaysia Case Reports. 

The case report presents details of the man, who complained of sudden central chest pain that lasted for 1 day. The pain was pressing in nature and was accompanied by diaphoresis and dyspnea. 

The patient was admitted with a working diagnosis of unstable angina. During admission, his physicians incidentally noticed a painless bluish discoloration in his toes. The patient disclosed that the discoloration started on the day that he was admitted, and that this was the first time he had noticed it. 

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Further history-taking revealed that the patient had dark urine and a nonproductive mild cough for the previous 2 days. He denied constitutional symptoms or symptoms associated with connective tissue disease. 

Read more about CAD epidemiology 

Upon examination, no lymph nodes were palpable at the cervical, axilar, or inguinal areas. Cardiovascular examination was normal and peripheral pulses were present. No hepatosplenomegaly or stigmata of peripheral vascular disease was noted, with the possible exception of persistent acrocyanosis in his toes bilaterally.

The patient’s blood investigations agglutinated immediately, leading his physicians to suspect a possible CAD diagnosis. Further investigations confirmed the diagnosis: a peripheral blood smear revealed marked agglutination of erythrocytes with polycythemia, and the patient’s cold agglutinin titer was 1:1024 at 4 °C. 

Infectious screening and autoimmune workup were negative. A bone marrow biopsy revealed 15 small/medium paratrabecular lymphoid follicles consisting of a mixture of B and T cells negative to CD10 and CD30. Immunophenotyping of the bone marrow aspirate demonstrated a mature B lymphoid population with high kappa chain expression. 

“To the best of our knowledge in Malaysia, there has only been one case report on primary cold agglutinin disease published in 1999,” the authors wrote. “However, it is a disease that should be recognised owing to the potential for transformation to an aggressive lymphoma and also the possibility of disabling symptoms such as anemia and cold-induced symptoms.”


Thangatorai R, Koh EJ. Primary cold agglutinin disease: a case report. MJM Case Reports. Published online August 2022.