Strategies to overcome the diagnostic challenges of autoimmune hemolytic anemias

IntroductionThe direct antiglobulin test (DAT) or Coombs test is the cornerstone of the diagnosis of autoimmune hemolytic anemia (AIHA). It can be performed by several methods with different sensitivity and specificity and enables the distinction of warm, cold, and mixed forms, which require different therapies.Areas coveredThe review describes the different DAT methods, including the tube test with monospecific antisera, microcolumn and solid phase methods that are routinely accessible in most laboratories. Additional investigations include the use of cold washes and low ionic salt solutions, the identification of auto-Ab specificity and thermal range, the study of the eluate, and the Donath-Landsteiner test, available in most reference laboratories. Experimental techniques are the dual-DAT, flow cytometry, ELISA, immuno-radiometric assay, and mitogen-stimulated DAT, which may help the diagnosis of DAT-negative AIHAs, a clinical challenge with delayed diagnosis and possible improper therapy. Further diagnostic challenges include the correct interpretation of hemolytic markers, the infectious and thrombotic complications, and the possible underlying conditions (lymphoproliferative disorders, immunodeficiencies, neoplasms, transplants, and drugs)Expert opinionThese diagnostic challenges may be overcome by a 'hub' and 'spoke' organization among laboratories, a clinical validation of experimental techniques, and a continuous dialogue between clinicians and immune-hematologic laboratory experts.

Automated summary

The direct antiglobulin test (DAT) or Coombs test is essential for diagnosing autoimmune hemolytic anemia (AIHA). Different methods of DAT can distinguish between warm, cold, and mixed forms of AIHA, which require different treatments. Additional investigations, such as cold washes and identifying auto-antibody specificity and thermal range, help diagnose DAT-negative AIHAs.