A new study has found a higher risk of mortality and thromboembolic events (TEs) among some patients with cold agglutinin disease (CAD) compared with healthy individuals. The study, published in Blood, found that patients with CAD were twice as likely to die or have TEs than individuals without CAD.

“Although there is consensus on an increased risk of thromboembolic events (TEs) in patients with CAD, the evidence for the effect on mortality is mixed,” the authors wrote. “The objectives of this retrospective study were two-fold: 1) to evaluate whether patients with CAD in the US have a higher risk of mortality and TEs compared with a matched non-CAD population, and 2) to determine the association between CAD biomarkers and the risk of mortality and TEs.”

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The research team assessed 457 patients with CAD and 2285 matched healthy individuals from the OPTUM Electronic Health Record database in the US between January 2007 and January 2021. Mortality and TEs were evaluated during the study period and biomarker levels were assessed at baseline and over the follow-up period.

Patient data were adjusted for smoking, comorbidities, past TEs, and other confounding variables.

The results showed that patients with CAD with any level of anemia were at a significantly higher risk of death than those without anemia. Higher levels of anemia (moderate or severe) were associated with TEs, while those with mild anemia were not at increased risk of TEs.

Higher bilirubin levels, as a measure of ongoing hemolysis, were also associated with an increased risk of death.

To help manage the risk of TEs and death in patients with CAD, the authors recommend ongoing control of complement activation and its associated hemolysis.


Broome C, Barcellini W, Roeth A, et al. Hemolytic markers, mortality, and thromboembolic events in cold agglutinin disease (CAD): A retrospective analysis of the Optum Electronic Health Record database in the United States. Blood. Published online November 15, 2022. doi:10.1182/blood-2022-163232