Among patients with cold agglutinin disease (CAD), there is a 4-fold difference in the prevalence and incidence of disease between cold and warm climates, according to study results published in Blood. The investigators of the retrospective, multinational study stated that this was the largest study of patients with confirmed CAD to date.

Sigbjorn Berentsen, MD, PhD, of the department of research and innovation at Haugesund Hospital in Haugesund, Norway, and colleagues assessed data from patients with CAD at 24 centers in 5 countries with the aim of improving the general knowledge of the epidemiologic, clinical, and laboratory findings of CAD, and providing information on real-world, long-term outcomes of previously studied therapies.

The study included 232 patients with verified CAD (mean age at diagnosis, 68 years; male to female ratio, 0.56); 207 patients had confirmed CAD and 25 had probable CAD. Of the 119 patients with complete disease duration information available, nearly 60% were diagnosed within 1 year of clinical onset.

Continue Reading

For all patients, the median baseline hemoglobin level was 9.2 g/dL; 27% and 38% of patients had hemoglobin less than 8 g/dL and greater than 10 g/dL, respectively.

Venous thrombosis (38 events) was reported in 30 patients (12.9%) during follow-up. When adjusted for age, the observed number of events (n=14) during an 8-year period was greater than the expected number of events (n=8.4), suggesting increased risk for venous thrombosis in patients with CAD compared with the general population.

In addition, the study included follow-up data from 45 patients who participated in the Nordic 2017 rituximab-bendamustine trial. Results showed that the therapy yielded a 78% response rate with 53% complete responses and 24% partial response. The response duration was not reached after 88 months; 77% of patients had an estimated 5-year sustained remission.

When comparing data from patients in Norway and Lombardy in North Italy, the investigators found a 4-fold difference in prevalence (20 vs 5 cases/million, respectively) and incidence (1.9 vs 0.48 cases/million/year, respectively). The researchers suggested that these differences are likely attributable to the 7oC lower outdoor temperature in Norway, resulting in more symptomatic disease; however, genetic differences or unintended patient selection cannot be ruled out. The investigators also noted that the primary limitation of the study was its retrospective design.

Related Articles

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Berentsen S, Barcellini W, D’Sa S, et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients [published online May 6, 2020]. Blood. doi: 10.1182/blood.2020005674