Questions about cold sensitivity helped doctors suspect CAD in older woman

Questions about cold sensitivity helped doctors suspect cold agglutinin disease (CAD) as a possible cause of severe anemia, fatigue, and shortness of breath in a 93-year-old woman with heart disease, a case report suggests.

“Probable CAD was initially obscured by [heart disease, blood thinner use, and possible bleeding] and the decisive cold-related history emerged only after targeted questioning,” the researchers wrote.

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Cold sensitivity offers key clue to probable CAD

After investigating other possible causes, doctors came to suspect CAD based on a long history of cold sensitivity and the presence of cold-reactive antibodies and markers of red blood cell destruction — all findings consistent with CAD. With blood transfusions, cold avoidance, and other supportive care, her condition stabilized.

“This case emphasizes directed inquiry about temperature-related symptoms and careful calibration of diagnostic certainty when formal CAD testing is incomplete,” the researchers wrote.

The case was described in the study “Probable Cold Agglutinin Disease Presenting With Profound Anemia and Cardiopulmonary Decompensation in a 93-Year-Old Woman: A Case Report,” which was published in Cureus.

CAD is caused by self-reactive antibodies, called cold agglutinins, that attach to red blood cells in cold temperatures, causing the cells to clump together and eventually be destroyed. This destruction is called hemolysis.

This can cause symptoms such as poor circulation and anemia, which can lead to fatigue and shortness of breath. Anemia occurs when there are too few red blood cells or too little hemoglobin, the protein in red blood cells that carries oxygen.

Researchers in Poland described the case of a 93-year-old woman with several heart conditions that required medication. She also had limited mobility. She sought medical attention because of worsening leg swelling, shortness of breath, chest pain, and severe fatigue.

Blood tests point to possible red blood cell destruction

When she arrived at the hospital, her hemoglobin level was extremely low, at 5.1 g/dL, down from 9.7 g/dL about four months earlier. She also had a low red blood cell count and elevated levels of markers of kidney function and heart strain.

Because she was taking a blood thinner and had severe anemia, doctors initially suspected hidden bleeding. Her heart disease also offered a possible explanation for some of her symptoms. Imaging scans did not identify a source of bleeding, but hidden gastrointestinal bleeding was not fully ruled out.

By the second day, doctors had received a blood test result indicating cold-reactive antibodies, providing an early clue that her anemia might also involve immune-mediated hemolysis, in which the immune system destroys red blood cells, as happens in CAD.

Subsequent tests showed an elevated level of a marker of red blood cell destruction and an increased proportion of immature red blood cells. A Coombs test was also positive, detecting an antibody and an immune protein attached to red blood cells.

These findings, along with the detection of an IgM-kappa monoclonal protein, an antibody protein commonly associated with CAD, strongly suggested CAD.

Because measurements of cold agglutinin levels and thermal amplitude — the highest temperature at which the antibodies remain active — were unavailable, the researchers considered the findings strong evidence supporting probable CAD, rather than a confirmed diagnosis.

Limited tests for certain infections were negative, and imaging scans did not reveal definite signs of enlarged lymph nodes or an enlarged liver or spleen. However, an unidentified blood cancer or another secondary trigger remained possible.

After doctors discussed the probable CAD diagnosis and how cold exposure could trigger symptoms, the woman and her family reported that she had long been unusually sensitive to cold. She also described severe pain after eating cold foods or drinking cold beverages, along with pain in her limbs during cold weather.

“These symptoms had not been volunteered during the initial bleeding-focused evaluation,” the researchers wrote.

Supportive treatment helps stabilize woman’s condition

With blood transfusions, medications to remove excess fluid, cold avoidance, and other supportive care, her hemoglobin level rose to 9.3 g/dL and her symptoms improved. She was discharged 15 days after presentation and remained clinically stable about 12 weeks after discharge.

The woman was offered further invasive testing to investigate the underlying cause of her condition, but she declined. “The decision reflected her advanced age, frailty, [other health conditions], and preference to avoid burdensome procedures when the results were unlikely to change the planned conservative management,” the team wrote.

The researchers said the case shows how CAD can be difficult to recognize when its symptoms overlap with those of other conditions common in older adults.

The researchers said doctors should consider probable CAD in older patients with otherwise unexplained severe anemia and worsening heart and lung function, particularly when a Coombs test shows an immune reaction involving red blood cells and other tests show evidence of their destruction.

They also emphasized that a patient’s history may provide an important diagnostic clue, particularly when symptoms associated with cold exposure are not identified during the initial assessment.

“Directed questions about pain after cold food or beverages, cold-triggered limb symptoms, and habitual avoidance of cool environments may reveal clues that were not initially volunteered,” the researchers wrote.