Patients with cold agglutinin disease (CAD) may experience chronic hemolysis and anemia all year regardless of the season, according to a new article published in Transfusion.

Researchers found that patients had elevated levels of hemolysis markers including bilirubin and lactate dehydrogenase (LDH) across all 4 seasons, as well as similar levels of anemia severity.

The study found that while bilirubin and LDH levels were above normal all year and indicated chronic hemolysis, the LDH levels were significantly higher in the winter than in the summer (P <.001). Bilirubin levels were not significantly different between seasons.

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Over the study period, 204 thromboembolism events were reported including 94 venous, 39 arterial, and 71 that were cerebral. The adjusted rates for these events were not significantly different between fall, winter, and spring, compared to summer.

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The rates of healthcare resource utilization (HRU) included inpatient visits, outpatient visits, emergency room visits, and transfusion days. They were found to not be significantly different between seasons with the exception of outpatient visits between the summer and spring. During the summer, the rate of outpatient visits was 114.4 per 100 person-months compared to 127.5 per 100 person-months in spring (P =.011).

The authors were unsure of why this increase was observed in the spring. “These data suggest that the systemic burden of complement-mediated hemolysis, anemia, thromboembolism risk, and HRU in CAD persist year-round and patients with CAD warrant close monitoring irrespective of the season,” they said.

The authors cautioned that this data was collected from a national database that spans a wide range of climates in the US and that the database used only collected broad geographic regions to protect patients’ confidentiality, both of which might affect the study results.

“Seasonal temperatures vary markedly across different regions of the [US], and any given patient may reside in multiple regions throughout the year; this may decrease the amount of seasonal variation in the temperature patients are exposed to, potentially affecting study outcomes,” they explained.

A total of 594 patients were retrospectively identified from the Optum® de-identified Electronic Health Record dataset containing data from all 50 US states. The patients were predominantly older than 65 years (66%), White (86%), and female (62%). The highest concentration of patients was identified from the midwestern region of the US (43%) and the average patient age was 67 years but the median was 71 years.


Röth A, Fryzek J, Jiang X, et al. Complement-mediated hemolysis persists year round in patients with cold agglutinin disease. Transfusion. Published online November 23, 2021. doi:10.1111/trf.16745