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Cold agglutinin disease

Author: Sumitha Baskaran, 11/29/2025
Category: Red Cell: Hemolytic Anemia (HA) > Autoimmune Hemolytic Anemias > Cold-active antibodies > Cold agglutinin disease (CAD) > Secondary CAD
Published Date: 01/22/2026

A 73-year-old man with metastatic lung carcinoma on treatment presented with worsening anemia. He had received two units of packed red blood cells two days earlier. His initial complete blood count at room temperature showed spurious and incompatible RBC indices:

RBC: 0.78 ×10⁶/µL

HGB: 8.0g/dL

HCT: 8.4%

MCV: 107.5fL

MCH: +++++

MCHC: 94.9g/dl

RDW: 26.5%

RDW-SD: 73.9fL

The RBC histogram displayed a broad peak with a left shift, suggesting red cell agglutination. The peripheral smear demonstrated striking cold-induced red cell agglutination with large, compact clusters and disrupted morphology.

Because the findings were inconsistent with the clinical picture, the sample was incubated at 37 °C for 30 minutes and rerun. The post-incubation CBC showed complete correction of parameters:

RBC: 2.74 ×10⁶/µL

HGB: 7.8g/dL

HCT: 24.0%

MCV: 87.6fL

MCH: 28.5pg

MCHC: 32.5g/dl

RDW: 24.4%

RDW-SD: 73.1fL

The RBC histogram normalized, and agglutination resolved on repeat smear review. These changes confirmed that the initial abnormalities were artefacts caused by cold agglutinins.

Serologic studies demonstrated a strongly positive cold agglutinin titre (1:512), while Mycoplasma pneumoniae IgM was negative.

This case highlights the characteristic analyser artefacts produced by cold agglutinins and the importance of warming the specimen to obtain accurate red cell indices.

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