Case Presentation: A 63-year-old man with a history of heart failure and cold autoimmune hemolytic anemia secondary to Waldenstrom macroglobulinemia was admitted for shortness of breath. He was diagnosed with heart failure exacerbation and was being treated with intravenous diuresis with close electrolyte monitoring. His initial potassium reading was 6.2 mEq/L, but the sample was hemolyzed. The subsequent measurement of potassium was 5.9 mEq/L, once again hemolyzed. Despite drawing the blood sample without a tourniquet or fist-clenching technique, the third sample exhibited hemolysis as well. There was an initial concern about severe in vivo hemolysis, but all hemolysis indicators were stable. Potassium was repeated a fourth time, again taking all precautions to avoid pseudohyperkalemia, but this time, the blood was kept warm between the palms and taken to the lab immediately. Potassium was 3.7 mEq/L (non-hemolyzed), confirming in vitro hemolysis from exposure to a cold environment.
Discussion: Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia mediated by IgM autoantibodies causing agglutination at ≤37°C, activation of the classical complement pathway, or both [1]. This case illustrates how blood exposure to a cold environment can cause hemolysis, leading to pseudohyperkalemia, and how simple measures taken on blood sample transportation can prevent it.Our patient presented in New York City in the month of May when the average temperature ranges from 13 to 24° Celsius, and even cooler inside the hospital due to air conditioning. The patient did exhibit some low-level in vivo hemolysis, as indicated by his positive yet stable hemolytic markers, but not enough to cause true hyperkalemia. Hemolysis was accelerated when the blood was exposed to a comparatively cold environment, leading to pseudohyperkalemia. Not all patients with CAD will have in vitro hemolysis on blood collection, as several factors determine the degree of hemolysis: the concentration of the antibody, its thermal amplitude, and the concentration of complement components [2]. Thermal amplitude is the temperature within which a cold-reacting antibody can interact with the red cell. It is an important determinant of the ability of the antibody to initiate the activation of the complement [2]. Studies of CAD use heated syringes to prevent hemolysis due to cold exposure [2]. In our case, keeping the blood collection tube between the palms prevented hemolysis since the blood temperature stayed above its thermal amplitude. Another implication of this phenomenon is for hypothermic surgical procedures like cardiopulmonary bypass, where rapid agglutination and hemolysis can occur on cooling the body below thermal amplitude [3].
Conclusions: Inaccurate lab results can lead to additional unnecessary diagnostic tests as well as potentially harmful interventions. This case illustrates the possibility of in vitro hemolysis on cold exposure after blood collection in CAD, which can cause spurious hyperkalemia. Such hemolysis can be prevented by keeping the blood specimen warm at all times.