Stay Away From the Cold: An Unusual Case of Cold Agglutinin Disease Presenting as Recurrent Transient Ischemic...

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive IgM antibodies leading to complement-mediated hemolysis. While CAD-associated venous thromboembolism is recognized, its role in arterial thromboembolic events, particularly ischemic stroke, is poorly defined. We report an 84-year-old woman who developed acute onset upper left extremity weakness following exposure to sub-zero temperatures. She had a history of similar transient episodes during cold seasons and recurrent anemia. Physical examination revealed decreased muscle strength in the upper left extremity (Grade 4+ out of 5) and scleral icterus. Laboratory findings showed normocytic anemia, elevated reticulocytes, high lactate dehydrogenase, indirect hyperbilirubinemia, and undetectable haptoglobin levels. Peripheral smear showed erythrocyte agglutination. Direct antiglobulin test was positive for C3d and IgM, confirming CAD. Vascular imaging showed significant atherosclerotic disease with near-occlusive (>80%) stenosis of the right internal carotid artery. The patient's transient ischemic attacks were attributed to compromised cerebral perfusion due to severe carotid artery stenosis, exacerbated by anemia from cold-induced hemolysis in CAD. Cold exposure precipitated hemolysis, leading to acute anemia and increased blood viscosity, further reducing cerebral blood flow and oxygen delivery. Spontaneous resolution of symptoms upon rewarming supported the role of CAD in her neurological deficits. This case underscores the potential for CAD to induce neurological deficits in patients with significant carotid artery stenosis. Clinicians should consider CAD as a contributory factor in patients presenting with transient neurological deficits precipitated by cold exposure, especially when significant arterial stenosis is present.