CAD likely contributed to mini-strokes in woman, 84: Case report
Woman’s neurological problems triggered by cold, resolved with rewarming
Cold agglutinin disease (CAD) was the likely trigger of repeated mini-strokes in an 84-year-old woman with already compromised blood flow in the brain due to severe narrowing of a major artery that supplies blood to the brain, according to a case report from Portugal.
The underlying mechanisms of red blood cell destruction, or hemolysis, in CAD can increase blood viscosity (thickness and stickiness) and reduce blood flow and oxygen delivery to the brain. In a person with pre-existing brain blood flow deficits, this may lead to a temporary blockage of blood flow to the brain, ultimately resulting in symptoms of a stroke.
The woman developed temporary neurological problems, specifically arm and hand weakness, upon cold exposure, which cleared up after spending time in the warmer temperature of the hospital. “The spontaneous resolution of her symptoms upon rewarming supports the role of cold exposure and CAD,” the researchers wrote.
The case study, “Stay Away From the Cold: An Unusual Case of Cold Agglutinin Disease Presenting as Recurrent Transient Ischemic Attacks,” was published in Cureus.
CAD occurs when the immune system produces self-reactive antibodies called cold agglutinins that attach to red blood cells at temperatures cooler than the body’s normal temperature. This causes red blood cells to clump together, activating the complement cascade, part of the immune system, that marks the cells for hemolysis. This can cause symptoms like anemia, when the number of red blood cells is too low.
Blockages and stroke
The release of hemoglobin, the protein in red blood cells that transports oxygen, into the blood triggers blood clot-forming processes, and clumps of red blood cells or related molecules can block blood flow in tissues and organs as they travel through the bloodstream.
While CAD-associated hemolysis is known to increase the risk of blood flow blockage, “its association with arterial [blood clot-related] events, particularly ischemic stroke, remains controversial and poorly defined,” the researchers wrote.
Ischemic stroke refers to the blockage of an artery leading to the brain that results in the death of brain cells due to oxygen deficiency. The woman described in the case report had recurrent transient ischemic attacks triggered by cold. Transient ischemic attacks, also known as mini-strokes, are caused by a temporary blockage of blood flow to the brain.
The woman visited the emergency department with sudden weakness in her left arm and hand, as well as generalized fatigue. She couldn’t lift her arm or perform precise hand movements. The symptoms began shortly after she was exposed to sub-zero temperatures when she left home.
She reported a similar episode the previous winter, involving left side weakness that resolved on its own after some hours. She also experienced recurrent anemia during colder months, which was treated with supplements of iron (needed to produce hemoglobin) but with little improvement.
Physical examination confirmed her arm and hand deficits, while sensory tests and reflexes were normal. She had jaundice, or yellowing of the skin and/or whites of the eyes, which results from the accumulation in the blood of a molecule released with hemolysis.
Lab tests showed several signs of hemolysis, including low hemoglobin, increased counts of immature red blood cells, and high levels of an enzyme that’s released with hemolysis. A blood smear revealed red blood cell clumps, consistent with CAD.
While jaundice may also be a sign of liver disease, the woman reported no other symptoms suggestive of liver problems. An abdominal ultrasound found no abnormalities, ruling out that hypothesis.
A direct Coombs test, which checks whether antibodies and complement proteins are attached to red blood cells, came back positive for both. The woman also had high levels of cold agglutinins, confirming a diagnosis of CAD.
Her arm weakness partially eased, and she was admitted to the stroke unit for monitoring and further examination.
CAD and narrow arteries
Imaging scans showed no blood clots in the brain, but her right carotid artery, which runs up to the brain, was severely narrowed, blocking more than 80% of the blood vessel. The woman was found to have a near-complete blockage at the point where the artery splits into two branches, reducing blood flow to the brain, which together with CAD likely contributed to her transient ischemic attacks.
Her symptoms resolved completely during her hospital stay without specific treatment, but where she was exposed to warmer temperatures than those outside.
Her severe arterial narrowing could not be treated surgically, so the woman was started on medications to prevent blood clots lower blood cholesterol, whose high levels may ultimately cause arterial blockage.
Doctors recommended she avoid cold exposure and ensure “adequate thermal insulation year-round” to prevent hemolysis. “Given the resolution of hemolysis with conservative measures and the patient’s advanced age, immunosuppressive therapy or blood transfusions were not pursued,” the team wrote.
“Clinicians should consider CAD as a contributory factor in patients presenting with transient neurological deficits precipitated by cold exposure, especially when significant arterial stenosis [narrowing] is present,” the researchers wrote. “Further research is needed to elucidate the [disease] mechanisms connecting CAD with arterial ischemia and to develop tailored treatment strategies.”
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