Polyagglutination is a rare and underdiagnosed condition, characterized by agglutination of red blood cells(RBCs) with almost all ABO-compatible adult sera. Polyagglutination can occur when a cryptantigen is exposed on RBCs via microbial enzyme activity. Becausenearly all adults naturally produce antibodies against cryptantigens, transfusion of plasma can cause unexpected hemolysis and hematologic complications, such as thrombocytopenia and disseminated intravascular coagulation, in patients whose cryptantigens are exposed. We report a case of Glycine soja polyagglutination occurring in a 60-year-old African-American man with disseminated methicillin-resistant Staphylococcus aureus (MRSA) infection. Prior to transfusion, the patient developed severe anemia of unknown etiology. Following transfusion of 3 units of fresh frozen plasma (FFP), his RBC count could not be determined for 24 days because of RBC agglutination in his blood sample. In addition, the FFP transfusion correlated with the rapid development of severe, transfusionrefractory thrombocytopenia and anemia. The perplexed clinical team consulted the blood bank. A direct antiglobulin test demonstrated 1+ mixed-field reactivity with both monoclonal anti-IgG and anti-C3d. Lectin panel testing showed reactivity with only Glycine soja, confirming the condition. Subsequently, plasma components were avoided, and RBC and platelet (PLT) components were washed prior to transfusion. After a 44-day hospitalization involving the transfusion of 22 units of RBCs and 13 units of PLTs, the patient was discharged to a long-term care facility. The patient's confounding hematologic complications can best be explained by polyagglutination, which developed secondary to the severe MRSA infection. The FFP transfusion likely passively transferred antibodies that bound to the patient's RBC cryptantigens, leading to RBC agglutination and anemia. The development of severe thrombocytopenia may be related to cryptantigen exposure on the patient's PLTs. Although difficult to identify, polyagglutination needs to be recognized to appropriately manage hemotherapy. The purpose of this case study is to report hematologic complications following FFP transfusion in a patient with Glycine soja polyagglutination, a rarely described condition.