An IgM Lambda Monoclonal Antibody in a Patient with Anti-Pr Cold Agglutinin Causing Erythrocyte Agglutination and Catastrophic Thrombosis

Erythrocyte agglutination causing microvascular occlusion is a rare albeit clinically significant event. This is seen in cold agglutinin disease and in cerebral malaria caused by Plasmodium falciparum. We studied a patient with autoimmune hemolytic anemia, characterized by massive hemolysis and the presence of both an anti-Pr antibody and a cold hemagglutinin. In addition, he suffered from catastrophic mesenteric ischemia necessitating surgical resection and extensive and multiple ischemia strokes. His surgical specimens, including colon, ileum and gall bladder, were studied with informed consent. Eluate from his agglutinated erythrocytes showed that he had an IgM lambda monoclonal antibody against the Pr antigen. The patient’s peripheral blood showed extensive erythrocyte agglutination that was worse at cold temperatures. H&E staining of the colon and ileum showed ischemia and necrosis with widespread microvascular occlusion caused by agglutinated erythrocytes. To characterize the intravascular agglutinated erythrocytes, immunoperoxidase staining was done and positive for IgM and lambda light chain and negative for IgG and kappa light chain. We thus concluded that the cold agglutinin on the intravascular agglutinated erythrocytes was an IgM lambda. To investigate why the circulating agglutinated erythrocytes resulted in widespread microvascular occlusion, we studied adhesive molecules including CD 62E (E-selectin), CD62P (P-selectin), CD54 (ICAM-1) and CD 106 (VCAM-1) and found all of them expressed on the agglutinated erythrocytes within the occluded vessels and on the endothelial cells of the involved vessels. The data suggests that the endothelial cells were activated at the site of vascular occlusion, thereby promoting adhesion of the agglutinated erythrocytes to the vascular endothelium.