Evidence Suggesting Complement Activation and Haemolysis at Core Temperature in Patients with Cold Autoimmune Haemolytic Anaemia

BACKGROUND: It is unclear why haemolysis may somewhat persist in patients with cold autoimmune haemolytic anaemia (cAIHA) at 37 °C (core temperature). METHODS: Seven patients with cAIHA were included in this study. Serological testing was performed using standard techniques. Bound autoantibodies (aab) on patients’ RBCs were analysed by the direct antiglobulin test (DAT), dual antiglobulin test (DDAT) and flow cytometry (FC) using pre-warmed RBCs (37 °C). Temperature-dependent complement binding was determined by incubation of patients’ serum samples with group O RBCs and fresh serum complement. RESULTS: The DAT was strongly positive with anti-C3d in all cases, independent of season and outside temperature. Haemolysis usually improved during warm periods of time, but decompensated following febrile infections, and persisted throughout the year, though exposure to the cold was strictly avoided. In addition, trace amounts of IgM aab were infrequently detectable on patients’ RBCs even at 37 °C, and complement activation was demonstrated following incubation of RBCs with the causative aab at 37 °C. CONCLUSIONS: Binding of trace amounts of IgM aab at 37 °C may provide an explanation for the durable C3d-positive DAT and haemolysis in patients with cAIHA.