Diagnostic algorithm of AIHA. The DAT or Coombs test is the cornerstone of diagnosis, and allows the distinction of the different forms of AIHA. wAIHA is the most common form, accounting for 60% to 70% of all cases; the DAT is positive with anti-IgG antisera (70% of all wAIHA) or anti-IgG plus C at low titer. Cold agglutinin disease (CAD; 20% to 25% of all AIHAs) is characterized by DAT positivity with anti-C antisera and high titer of cold agglutinins. In mixed forms (5% to 10% of all AIHAs), the DAT is positive for IgG plus C, and cold agglutinins are present at high titer. The atypical forms (∼10% of all AIHAs) include DAT⁻, IgA, and warm IgM-driven AIHAs. Finally, it is necessary to record the very rare form named paroxysmal cold hemoglobinuria (1% to 3% of all AIHAs) sustained by the biphasic Donath-Landsteiner hemolysin. ELISA, enzyme-linked immunosorbent assay; LISS, low-ionic salt solution; MS-DAT, mitogen-stimulated DAT; PEG, polyethylene glycol; PNH, paroxysmal nocturnal hemoglobinuria.