Table 2.
Diagnostic criteria for cold agglutinin disease.
| Level | Criteria | Procedures, comments and reminders |
|---|---|---|
| Required for diagnosis | Chronic hemolysis | As assessed by hemoglobin levels and biochemical markers of hemolysis |
| Polyspecific DAT positive | Performed in most laboratories but insufficient for diagnosis | |
| Monospecific DAT strongly positive for C3d | DAT is usually negative for IgG, but occasionally weakly positive | |
| CA titer > 64 at 4oC | Blood specimen must be kept at 37-38oC from sampling until serum/plasma has been removed from the clot/cells | |
| No overt malignant disease or relevant infection | Clinical assessment for malignancy. Radiology as required. Exclusion of recent infection with Mycoplasma or EBV | |
| Confirmatory but not required for diagnosis | Monoclonal IgMκ in serum (or, rarely, IgG or λ phenotype) | Blood specimen must be kept at 37-38oC from sampling until serum/plasma has been removed from the clot/cells |
| Ratio between κ and λ positive B-cells > 3.5 (or, rarely, <0.9) | Flow cytometry in bone marrow aspirate | |
| ‘CA-associated lymphoproliferative disorder' by histology | Bone marrow biopsy |
CA, cold agglutinin; DAT, direct antiglobulin test; EBV, Epstein-Barr virus; Ig, immunoglobulin. Previously published by Berentsen (23), reused under general permission, slightly modified. Copyright: The American Society of Hematology.