Positive direct antiglobulin tests in cancer patients on immune checkpoint inhibitors: A case series from India

Tumour cells activate immune checkpoints such as programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) signalling pathways to inhibit T lymphocyte activation and thus escape from immune surveillance. Immune checkpoint inhibitors (ICPis) reactivate T lymphocytes to recognize cancer cells by blocking CTLA-4 or PD-1. Autoimmune haemolytic anaemia is a rare, but often severe, complication of ICPis. Therefore, we performed a retrospective clinical case review, including serologic, haematology, and biochemistry laboratory results, of three patients who developed autoantibodies to erythrocytes following treatment with pembrolizumab, an anti-PD-1 inhibitor. Serologic testing of blood samples from these patients showed their red cells were positive for direct antiglobulin test (DAT + for IgG in two cases and IgG with C3d in one case). Antibody detection test was negative. No patient had clinical and laboratory features of haemolysis. There were no additional immune-related adverse events. IgG antibodies coating red cells were neither IgG1 nor IgG3 in class and elution was found negative in all. In conclusion, immunohaematology laboratories should be aware of the possibility of erythroid autoantibodies and their nature in cancer patients receiving ICPis. The result of a positive DAT should be interpreted carefully in these patients to exclude other possible causes of anaemia.