Abstract
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.
Highlights
Autoimmune hemolytic anemia (AIHA) is an acquired form of hemolytic anemia in which autoantibodies target red blood cell (RBC) membrane antigens, inducing cell rupture
An autoimmune lymphoproliferative syndromes (ALPS) screening panel was positive with a score of 4/4, and follow-up sequencing on the ALPS gene panel
Since his hemolysis was fairly well compensated, the patient was started on sirolimus without concurrent steroid treatment for his warm AIHA (w-AIHA), with resolution of hemolysis by the time of follow-up 4 months later and no palpable splenomegaly after a year
Summary
Autoimmune hemolytic anemia (AIHA) is an acquired form of hemolytic anemia in which autoantibodies target red blood cell (RBC) membrane antigens, inducing cell rupture (lysis). Since his hemolysis was fairly well compensated, the patient was started on sirolimus without concurrent steroid treatment for his w-AIHA, with resolution of hemolysis by the time of follow-up 4 months later and no palpable splenomegaly after a year This case illustrates several points worth noting regarding w-AIHA in childhood: while it is prudent to consider other possible causes of hemolysis, the clinical suspicion of AIHA with a new-onset hemolytic anemia has to be pursued further with an enhanced DAT assay. Autoimmune lymphoproliferative syndromes (ALPS) screening panel was positive with a score of 4/4, and follow-up sequencing on the ALPS gene panel (including the genes CASP8, CASP10, FADD, FAS, FASLG, ITK, KRAS, MAGT1, NRAS) was conducted and detected a variant of uncertain significance (VUS) in FAS: c.710C > T (p.A237V) IgG autoantibodies may bind to the RBCs at a relatively low level, causing hemolysis, but being below the threshold of detection for the commonly performed DAT, while flow cytometry is more sensitive to detect these low levels of antibodies bound to RBCs [12]
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