A Last Resort Modality Using Cryofiltration Apheresis for the Treatment of Cold Hemagglutinin Disease in a Veterans Administration Hospital

Abstract

Cold hemagglutinin disease is a cold autoimmune hemolytic anemia (cAIHA) caused by an autoantibody, such as IgM, directed against the I-antigen present on the surface of erythrocytes. Cold exposure can activate this system causing hemolysis, hemagglutination, microvascular thrombosis, or acrocyanosis. Thus, surgical procedures requiring hypothermia, such as coronary artery bypass surgery, present a significant problem in patients with cAIHA. The purpose of this study was to evaluate the safety and effectiveness of cryofiltration apheresis (CFA), used as a last resort, for the treatment of cAIHA. Effectiveness was evaluated by clinical assessment and laboratory evaluations of cold agglutinin titer, immunoglobulins, and other plasma proteins. Safety was evaluated by vital signs, monitoring, and laboratory measurements of complements, hematology and blood chemistry. Five patients with cAIHA were treated by CFA using the cryoglobulin (CG) filter (Pall Medical, Ann Arbor, MI, USA). Four patients received only one CFA procedure, while one patient received four CFA treatments. The cold agglutinin titers were fairly low, ranging from 1 : 1 to 1 : 2048. However, a wide thermal amplitude(4-37 degrees C) was observed in most patients. Two out of five patients responded favorably with reduction in titer. The two responders had acute forms of cAIHA with serum positive for cryoglobulins. The three non-responders had chronic forms of cAIHA with negative cryoglobulins. CFA effectively removed cryoprotein precipitates while conserving other plasma components. The CG filter was biocompatible with no complement activation or observed complications due to CFA or CG filter. While the mechanism of action in treating this type of patient population with CFA is unknown, the plausible theories are discussed.