Cold agglutinins are autoantibodies that cause agglutination of red blood cells at colder temperatures.  Therefore, cold agglutinins are important to recognize in patients who receive intentional hypothermia.  Typical therapeutic uses of hypothermia include cold cardioplegia during cardiovascular surgery and in cases following cardiac arrest for neurologic stabilization. Hypothermia in patients with cold agglutinins may cause severe, life threatening complications due to hemolysis and microvascular occlusion. Some of the most commonly reported complications include acrocyanosis, stroke, and death.

The patient’s history may reveal cold intolerance and acrocyanosis. A focused review of systems could ask screening questions such as “How does cold weather affect your fingers?” Clues to recognition on physical exam are non-specific and include pallor, jaundice, lymphadenopathy, and hepatosplenomegaly.

Classic laboratory findings typically reveal an abnormal CBC with MCHC > 36, often with a comment attached to the report describing the presence of a probable cold agglutinin. Hemoglobinuria may be present. Routine Blood Bank Type and Screen testing may also alert to the presence of a cold autoantibody.

The clinical significance of these antibodies depends on their etiology and strength, although most cold agglutinins detected in the laboratory have little to no clinical significance. Healthy adults may have naturally occurring cold agglutinins in low concentrations. Pathologic cold agglutinins may be idiopathic, acutely present in the recovery phase of infections (Mycoplasma, mononucleosis, CMV), or occur in the setting of a B-cell lymphoproliferative disease. Strength and reactivity are dependent on antibody concentration (titer) as well as the temperature in which agglutination occurs, known as the thermal amplitude.

Whenever a cold agglutinin is suspected, a confirmatory cold agglutinin test can be ordered. Patients should be referred to a Hematologist, when indicated, and educated on the importance of cold avoidance.  Pathologists are also available to answer specific questions about cold agglutinins detected within the laboratory.

– Dr. Bruce Walker, Medical Director at PAH