Any patient with biochemical features of haemolysis and a positive direct Coombs test. The pattern of reactivity (IgG vs. C3) is the primary diagnostic classifier.
When Not to Rely on This Score Alone
DAT negative AIHA — a negative DAT does not 100% exclude immune haemolysis (requires specialized assays).
Asymptomatic positive DAT — many healthy individuals or those with hyperglobulinemia have a positive DAT without haemolysis.
To monitor response to therapy — clinical and biochemical markers (Hb, LDH, Retics) are superior for monitoring treatment response.
Section 2
Formula & Logic
Patterns of Reactivity
Pattern
IgG
C3d
Possible Diagnoses
Warm AIHA
+
±
Idiopathic, SLE, CLL, Drugs
Cold Agglutinin (CAD)
-
+
Idiopathic, Mycoplasma, EBV, Lymphoma
Mixed AIHA
+
+
Idiopathic, SLE
PCH
-
+
Syphilis (classic), Viral (children)
Drug-Induced
+
±
Penicillins, Cephalosporins, NSAIDs
Section 3
Pearls/Pitfalls
Thermal Amplitude
Warm AIHA antibodies (usually IgG) react optimally at 37°C. Cold antibodies (usually IgM) fix complement (C3d) at 4°C; thus, the DAT detects the C3 remnants on the red cell, not the IgM itself which dissociates at warmer temperatures.
The Donath-Landsteiner Test
Paroxysmal Cold Haemoglobinuria (PCH) typically shows a C3-only positive DAT. Secure diagnosis requires the biphasic Donath-Landsteiner functional assay.
Section 4
Literature
Development
The DAT (Direct Coombs Test) was first described by Coombs, Mourant, and Race in 1945. It remains the foundation of immuno-hematology for detecting in-vivo sensitization of red blood cells.