A Case Report of the "Pathological Triad": Infection-Induced Cold Agglutination with Hemolytic Anemia

Although Mycoplasma pneumoniae is a recognized cause of community-acquired pneumonia, its hematologic complications are often overlooked in primary care settings. Here, we present a case that exemplifies the diagnostic challenges associated with Mycoplasma pneumoniae-induced cold agglutination and hemolytic anemia.

Complete blood count analysis was performed using an automated hematology analyzer, with discordant erythrocyte indices prompting thermal correction via 37℃ water bath incubation. Serum biochemical markers, including Creatine Kinase-MB (CKMB), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Total Bilirubin (TBIL), and Direct Bilirubin (DBIL) were quantified using an automated biochemistry analyzer. Mycoplasma pneumoniae IgM and DNA were detected via immunochromatography and PCR, respectively. A direct anti-human globulin test (Coombs test) was conducted using standard reagents. Peripheral blood smears were examined microscopically for erythrocyte agglutination and morphology.

Positive results for the Mycoplasma pneumoniae IgM antibody and DNA tests confirmed that the patient had active infectious pneumonia. Initial results of the automated blood cell analysis were as follows: RBC (1.6 x 1012/L), HGB (111 g/L), MCH (69.4 pg), and MCHC (703 g/L). After a 37℃ water bath, the results changed to: RBC: 3.73 x 1012/L, HGB: 113 g/L, MCH: 30.1 pg, MCHC: 337 g/L. The RBC count, HGB, and HCT results were significantly lower than those recorded a week earlier, especially the HGB result, which decreased by 46 units. The Coombs test was positive. There were significantly elevated levels of biochemical markers (CKMB, LDH, and HBDH). Mild elevations were also noted in TBIL and DBIL. No comorbidities or hemolytic triggers were identified. Taken together, the evidence suggests that the patient experienced cold agglutination and progressive hemolysis following Mycoplasma pneumoniae infection.

This case establishes three evidence-based protocols for frontline practice. First, consider testing for Mycoplasma pneumoniae in patients with unexplained anemia following a respiratory infection. Second, apply thermal correction to blood samples when the MCHC results do not match the other erythrocyte parameters. Third, monitor for hemolysis for at least two weeks after Mycoplasma pneumoniae IgM is detected.