Acute paroxysmal cold haemoglobinuria; a case report and literature review

Paroxysmal cold hemoglobinuria (PCH) is a very rare subtype of autoimmune hemolytic anemia caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria, typically after exposure to cold temperatures. The acute onset PCH occurs following viral illnesses whilst the chronic form is secondary to hematological malignancies and tertiary syphilis. It is a complement mediated intravascular hemolytic anemia associated with a biphasic antibody against the P antigen on red cells. We describe a three year child who had acute onset PCH following likely viral infection. The diagnosis was confirmed by demonstration of strongly positive Donnath Landsteiner antibodies. She made a gradual recovery with supportive treatment, ten days following the initial detection of haemolysis. Parents were educated about the need to avoid cold exposure to prevent precipitation of further haemolysis and folic acid was commenced to assist the recovery of erythropoiesis. Bangladesh Journal of Medical Science Vol.20(3) 2021 p.654-657

Autoimmune Hemolytic Anemia in the Pediatric Setting

Autoimmune hemolytic anemia (AIHA) is a rare disease in children, presenting with variable severity. Most commonly, warm-reactive IgG antibodies bind erythrocytes at 37 °C and induce opsonization and phagocytosis mainly by the splenic macrophages, causing warm AIHA (w-AIHA). Post-infectious cold-reactive antibodies can also lead to hemolysis following the patient’s exposure to cold temperatures, causing cold agglutinin syndrome (CAS) due to IgM autoantibodies, or paroxysmal cold hemoglobinuria (PCH) due to atypical IgG autoantibodies which bind their target RBC antigen and fix complement at 4 °C. Cold-reactive antibodies mainly induce intravascular hemolysis after complement activation. Direct antiglobulin test (DAT) is the gold standard for AIHA diagnosis; however, DAT negative results are seen in up to 11% of warm AIHA, highlighting the need to pursue further evaluation in cases with a phenotype compatible with immune-mediated hemolytic anemia despite negative DAT. Prompt supportive care, initiation of treatment with steroids for w-AIHA, and transfusion if necessary for symptomatic or fast-evolving anemia is crucial for a positive outcome. w-AIHA in children is often secondary to underlying immune dysregulation syndromes and thus, screening for such disorders is recommended at presentation, before initiating treatment with immunosuppressants, to determine prognosis and optimize long-term management potentially with novel targeted medications.