Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association

Abstract

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

Figure 1

Diagnostic work up. neg: negative; DAT: direct antiglobulin test; pos: positive; DL: biphasic haemolysins of Donath-Landsteiner; IAT: indirect antiglobulin test; LISS: low ionic strength; PEG: polyethylene glycol; ELISA: enzyme-linked immunosorbent assay; IRMA: immunoradiometric tests; MS-DAT: direct antiglobulin test after mitogenic stimulation.

Figure 2

First-line therapy of warm antibody AIHA. If steroid induces no response at 3 weeks, having excluded a different diagnosis, the patient is shifted to second line treatment (8.6-A). For responsive patients, initial steroid therapy should last at least 4 weeks (8.6-B); in the case of CR, steroid can be tapered (8.8-B); in the case of PR, the full dosage should be continued for 2 more weeks. In any case, after 6 weeks, steroid must be tapered (8.4-B). Tapering schedule: the full dosage is reduced by 25–50% over 4 weeks, thereafter, the reduction must be gradual, in order to extend the treatment for at least 6 months (7.8-C); if a relapse or exacerbation of the hemolysis is observed, during the tapering process, the dosage should be brought back at the previous level (8.2-C). AHIA: autoimmune haemolytic anaemia; PDN: prednisone; Ig: immunoglobulin; NR: no response, CR: complete response, PR: partial response.