Therapeutic plasma exchange for refractory Mycoplasma pneumoniae-associated cold agglutinin syndrome: A case report

Cold agglutinin syndrome (CAS) secondary to Mycoplasma pneumoniae typically self-resolves with antimicrobial therapy and supportive care. Therapeutic plasma exchange (TPE) has been described as an adjunct therapy in refractory CAS, but there is limited data on its use in M. pneumoniae-associated CAS.

A 26-year-old male developed severe hemolytic anemia 3 weeks after initial M. pneumoniae diagnosis. Initial hemoglobin was 8.2 g/dL with marked hemolysis (lactate dehydrogenase 1398 U/L, total bilirubin 4.0 mg/dL, haptoglobin <10 mg/dL). Antibody screen was positive for cold antibody. Direct antiglobulin test was C3-positive. Despite appropriate antimicrobial therapy, he required 17 units of packed red blood cells over 20 days of admission.

TPE was initiated on day 11 for refractory hemolysis. Four sessions were performed (on days 11, 14, 17, 18). Antibody screens became negative post-TPE and markers of hemolysis improved. Following the final 1.5 plasma volume exchange, the patient achieved his longest transfusion-free interval (5 days). Research flow cytometry demonstrated elevated surface IgG and C3 on red cells pre-exchange that decreased over the course of TPEs but remained above baseline at discharge. The patient required three additional units of red cell transfusions post-discharge but achieved transfusion independence by day 30. Total transfusion requirement was 20 units.

This case of M. pneumoniae-associated CAS highlights atypical features including failure of antimicrobial therapy and supportive care alone, exceptional transfusion needs, and ongoing hemolysis despite TPE. TPE may serve as adjunctive therapy in transfusion-dependent refractory CAS in the setting of M. pneumoniae infection.