Cryofibrinogenemia as a cause of <scp>ABO</scp> forward/reverse discrepancy and positive antibody screen result

A 79-year-old female with a history of marginal zone lymphoma, who recently underwent laminectomy for spinal stenosis, presented to the emergency department with wound dehiscence, skin necrosis, and poor wound healing. She was admitted for intravenous antibiotics. An initial complete blood count revealed a hemoglobin of 7.1 g/dL, upon which a blood type and antibody screen were ordered. An automated gel agglutination assay (IH 500 Bio-Rad Laboratories, Inc.) performed on an EDTA sample showed a forward blood group and typing result of A Rh(D)-positive, but a reverse result of O Rh(D)-positive (Figure 1). The antibody screen result was positive with two group O reagent cells. Manual tube test methodology demonstrated a non-discrepant group A result and negative antibody screen. Identical results were obtained with a subsequent specimen. The previous specimen was retrieved after refrigeration, and a visible precipitate layer was seen at the interface of the plasma and red blood cell layers, raising suspicion for cryoglobulins (Figure 2). Serum cryoglobulin studies were negative. A peripheral blood smear did not show rouleaux formation. Serum and urine protein electrophoresis revealed an IgM monoclonal spike of 2.7 g/dL. Retrospective evaluation of the debridement specimen revealed Periodic acid-Schiff positive precipitate globules in the blood vessels, not previously recognized (Figure 3). These findings were consistent with cryofibrinogenemia, providing an explanation for the patient's poor wound healing. We present this case as a lesson on how immunohematology methods in the blood bank can provide diagnostic information beyond pre-transfusion compatibility, if the clinical context is considered. The authors declare no conflicts of interest. All figures are originals.