Table 3.

Diagnostic evaluation of children with AIHA.

Initial Laboratory Evaluation of AIHA

Complete blood count (CBC) with differential Reticulocyte count (absolute reticulocyte count (ARC) is preferable) Peripheral blood smear review

Direct antiglobulin test (DAT) Type and Screen [Screen is performed by the Indirect Antiglobulin Test (IAT)] Follow-up evaluations include: Cold agglutinin titer when DAT is positive for C3 Donath-Landsteiner antibody test when paroxysmal cold hemoglobinuria (PCH) is suspected Enhanced DAT (Super-Coombs test) if presentation is consistent with AIHA but conventional DAT is negative

Serum markers of hemolysis (i.e., total and unconjugated bilirubin, lactate dehydrogenase, haptoglobin) Liver and kidney function tests

Urine hemoglobin and hemosiderin evaluation may be used to differentiate intravascular (positive result) versus extravascular hemolysis

Bone marrow aspirate and biopsy in atypical cases where there is a concern for underlying malignancy, e.g., concurrent thrombocytopenia and/or neutropenia, unusual or prolonged reticulocytopenia, lymphadenopathy or organomegaly without evidence of concurrent EBV infection.

In cases of w-AIHA, consider possibility for underlying causes

Screen for primary immune disorder (PID) on a sample obtained before treatment initiation IgG, IgM, IgA quantification Lymphocyte subpopulations by flow cytometry Autoimmune lymphoproliferative syndrome (ALPS) screening panel by flow cytometry Follow-up testing as needed with next-generation sequencing on ALPS or PID gene panels

Screen for rheumatologic diseases (frequently indicated in teenager females) Antinuclear antibodies Anti-double-stranded DNA antibodies

HIV testing