Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia caused by antibodies—typically immunoglobulin M (IgM), and less frequently IgA or IgG—that target antigens on the surface of erythrocytes. Although the etiology may involve infections or immunologic disorders, most cases are idiopathic. The clinical picture results from hemolysis triggered by antibodies that become active at cold temperatures, leading to degenerative changes in the erythrocyte membrane and autoagglutination. This causes a drop in erythrocyte count and hematocrit, while MCV, MCH, and MCHC values appear markedly elevated. Peripheral blood smears often reveal erythrocyte agglutination. Here in, we present a case of cold agglutinin disease secondary to COVID-19 infection.

A 14-year-old previously healthy girl was initially treated with amoxicillin-clavulanate for upper respiratory tract infection symptoms, including fever and cough. Her symptoms worsened, and she tested positive for COVID-19 at an outside hospital. She was diagnosed with lobar pneumonia, and significant anemia noted during follow-up prompted her referral to our institution, Türkiye.

Upon admission to our pediatric intensive care unit, three consecutive hemogram samples were clotted and could not be analyzed. Venous blood gas revealed hemoglobin (Hb) of 4.2 g/dL. Biochemical analyses showed LDH: 724 U/L (range 110-295 U/L), total bilirubin: 1.85 mg/dL (range 0.3-1.2 mg/dL), direct bilirubin: 0.29 mg/dL (range 0-0.2 mg/dL), and haptoglobin: 0.38 g/L (range 0.35-2.5 g/L). Direct Coombs test was negative. Peripheral smear demonstrated erythrocyte agglutination clusters. Blood samples were delivered to the laboratory in warm water immediately after collection to prevent in vitro agglutination. Repeat tests showed Hb: 8.2 g/dL, MCV: 100 fL, and a markedly elevated MCHC of 683 g/dL.

Quantitative cold agglutinin testing could not be performed due to technical limitations at our center. In addition to pneumonia treatment, the patient was started on methylprednisolone at 2 mg/kg/day for presumed cold agglutinin disease. She was discharged on day 10 of treatment and her steroid therapy was tapered and discontinued by day 21. At follow-up on day 21, the patient’s hemoglobin had increased to 13.9 g/dL, and no erythrocyte agglutination was observed on peripheral smear.

This case highlights a rare pediatric presentation of cold agglutinin disease associated with COVID-19 infection, complicated by severe hemolysis and lobar pneumonia. Early recognition and a multidisciplinary approach including corticosteroids and supportive care played a critical role in the patient's favorable outcome.