Chemotherapy triggers cold agglutinin disease in woman with breast cancer
Researchers warn paclitaxel may spark immune attack on blood in rare case
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A woman in her 50s battling advanced breast cancer developed a rare blood disorder called cold agglutinin disease (CAD) as a direct complication of her chemotherapy treatment. According to a recent case study, the woman’s immune system began attacking her own red blood cells after she received paclitaxel.
While the patient saw a partial recovery after being treated with rituximab, a medication commonly used off-label for CAD, the onset of the disorder forced doctors to stop her chemotherapy. Despite switching to other treatments, her cancer continued to spread, and she died five years after her initial diagnosis.
Researchers say this case serves as a critical reminder for doctors to watch for unusual patterns of anemia during cancer treatment. Recognizing these rare toxicities early is essential, as they can completely change a patient’s treatment path and limit their options for fighting the underlying cancer.
“This case highlights how an uncommon, treatment-related immune complication can redefine the therapeutic trajectory of a patient with advanced breast cancer,” researchers wrote. “By shifting the focus from disease progression to treatment toxicity, it illustrates the importance of recognizing unusual patterns of anemia, integrating [blood disease] expertise, and adapting [body-wide treatments] accordingly.”
The case study, “Cold agglutinin syndrome in a patient with metastatic breast cancer: a Case Report,” was published in Frontiers in Medicine.
How CAD affects the body
CAD is caused by cold agglutinins, self-reactive antibodies that bind to red blood cells at cold temperatures, causing them to stick together. This activates the complement pathway, a component of the immune system, ultimately leading to red blood cell destruction (hemolysis) and anemia (low red blood cell levels).
The disease can be classified as primary when it happens on its own, or secondary (often called cold agglutinin syndrome, or CAS) when it is triggered by an infection, blood cancer, or, as seen in this case, solid tumor treatments. Although CAD is rarely linked to solid tumors, evidence suggests that certain anticancer drugs may be the true trigger.
In this specific case from Portugal, the patient, who had a previous history of obesity, high blood pressure, abnormal blood levels of fats, and anxiety, was diagnosed with breast cancer in 2019. She underwent surgery to remove the tumor, followed by chemotherapy, radiotherapy, and hormonal therapy.
The cancer was later found to have spread, or metastasized, to her bones, liver, and lymph nodes in 2022, and the woman started first-line therapy for metastatic breast cancer, which led to a partial response. She later experienced cancer progression and was prescribed paclitaxel, as third-line treatment, in 2024.
After four weekly paclitaxel doses, the woman was admitted to the hospital with severe anemia, as reflected by very low levels of hemoglobin, the protein that carries oxygen in red blood cells.
Blood tests showed signs of hemolysis, including elevated bilirubin, lactate dehydrogenase, and proportion of immature red blood cells. Analysis of a smear of blood on a glass slide showed red blood cell clumping that eased when the slide was rewarmed before preparation.
This led to a direct Coombs test, which confirmed that immune proteins were attacking her red blood cells. Because the symptoms appeared so abruptly after she started paclitaxel, doctors concluded the drug was likely responsible.
To manage the sudden blood disorder, the woman received blood transfusions through a warmer and a course of corticosteroids. When those treatments showed limited success, doctors turned to rituximab. This intervention helped stabilize her blood levels and reduce the destruction of her red blood cells.
However, the recovery was bittersweet. Because paclitaxel was identified as the trigger, it had to be permanently discontinued. The medical team shifted to low-dose chemotherapy, but without the more aggressive options, the cancer eventually overwhelmed her system.
The researchers noted that while CAD was successfully managed, the complication “reshaped the therapeutic trajectory.” They emphasized that a multidisciplinary approach is vital for patients with these rare immune reactions, even if the ultimate outcome remains driven by the primary cancer.
