CAD Active Year Round, Not Just in Cold Weather, New Study Shows

Marisa Wexler MS avatar

by Marisa Wexler MS |

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People with cold agglutinin disease (CAD) show signs of red blood cell destruction year round, not just when the weather is cold, a new study highlights.

These findings suggest that CAD patients should be closely monitored at all times, regardless of season, according to researchers.

The study, “Complement-mediated hemolysis persists year round in patients with cold agglutinin disease,” was published in the journal Transfusion.

CAD is an autoimmune disorder caused by self-targeting antibodies called cold agglutinins. At low temperatures, cold agglutinins bind and destroy red blood cells, which are responsible for carrying oxygen through the body. This results in anemia and other symptoms, such as weakness and fatigue.

Since cold agglutinins are more active at cold temperatures, it seems intuitive that CAD symptoms might generally be worse in colder weather. However, there is little data on the link between CAD symptoms and seasonal weather variation.

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Now, a team of scientists from the University of Duisburg-Essen, in Germany, the multinational pharmaceutical Sanofi, and science research company EpidStrategies, in Maryland, conducted an analysis using information from a commercial U.S. database that contains clinical data on about 14 million people across all 50 U.S. states.

“To our knowledge, this is the first study to evaluate seasonality [in markers of disease activity] in patients with CAD,” the team wrote.

The team identified 594 patients with CAD who had clinical data available between 2008 and 2016. Most patients were female (62%), white (86%), and from the Midwest part of the country (43%). The average age was 67.

Researchers looked for seasonal patterns in the results of laboratory tests related to red blood cell destruction.

Average levels of hemoglobin — the molecule that red blood cells use to transport oxygen through the body — were lowest in the winter (9.99 g/dL) and highest in the summer (10.19 g/dL), but none of the differences among seasons were significant. Notably, all of these levels were relatively low, as normal hemoglobin levels usually range from 12 to 17 g/dL.

Levels of lactate dehydrogenase (LDH), a marker of red blood cell destruction, followed a similar pattern. While average levels were significantly higher in the winter and spring than in the summer, average levels year-round were outside the normal range. Levels of bilirubin, another marker of red blood cell death, also were high across the different seasons.

Other analyses found few season-based differences in inpatient visits, outpatient visits, emergency room visits, or the use of blood transfusions. There also were no significant differences in the frequency of clotting-related events.

“These data suggest that the systemic burden of complement-mediated [red blood cell destruction], anemia, [blood clot] risk, and HRU [healthcare resource utilization] in CAD persist year round and patients with CAD warrant close monitoring irrespective of the season,” the researchers concluded.

The researchers did note some limitations to the study, including a lack of data on circulatory symptoms and that the database used only covered commercially insured patients from a single managed healthcare plan. Another issue was the possibility of frequent travel by patients.

“Seasonal temperatures vary markedly across different regions of the United States, 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,” the team wrote.