Hemolysis and thrombotic risk can persist throughout the year in patients with cold agglutinin disease (CAD) with substantial interindividual variability in disease severity, a new study published in the journal Transfusion recently found.

“Challenges some long-held assumptions, and demonstrates to treating physicians and patients alike that year-round vigilance for the monitoring and potential management of CAD is essential,” Christopher J. Patriquin and Katerina Pavenski responded in an editorial.

Patients with CAD did not present with significant seasonal variation in the levels of hemoglobin and bilirubin. Moreover, despite the median concentration of lactate dehydrogenase being higher in winter and spring than in summer, patients experienced persistent hemolysis throughout the year.

Continue Reading

Read more about CAD treatment

Transfusion days and the occurrence of thromboembolism events were also similar over the seasons. Patriquin and Pavenski discussed the current management of CAD, and how the treatment should be primarily focused on resolving the underlying lymphoproliferative disorder.

However, in some cases, this selected therapeutic approach may be associated with high toxicity or low efficacy, thereby compromising the success of the therapeutics.

“Control of persistent downstream effects may have a significant impact on preventing complications and improving outcomes,” they said.

Patients With Cold Agglutinin Disease Show Evidence of Symptoms Year-Round

The temporary use of B-cell targeted therapies can target the underlying cause and manage symptoms. However, long-term management of patients with CAD due to chronic hemolysis usually requires proximal complement inhibition.

In addition, terminal complement blockade may add value when used sporadically to address paradoxical intravascular hemolysis. This is particularly important while waiting for targeted therapy to work to protect patients from severe consequences.

Although these approaches can be used separately or together, Patriquin and Pavenski cautioned that each has associated risks, such as infection.


Patriquin CJ, Pavenski K. O, wind, if winter comes … will symptoms be far behind? Transfusion. Published online December 10, 2021. doi:10.1111/trf.16765