✅ Cold agglutinin disease (CAD) is defined as an AIHA mediated by cold agglutinins (CAs),
✅ CAD may be classified as primary and secondary
- Also called idiopathic CAD or simply CAD.
- No evidence of underlying disease such as aggressive lymphoma, other overt malignancies, or specific infections.
- Also called cold agglutinin syndrome
- Complicating other specific diseases, such as Mycoplasma pneumoniae pneumonia, Epstein-Barr virus infection, or aggressive lymphoma
✅ CAD accounts for about 15% of autoimmune hemolytic anemias (AIHA).
✅ Cold agglutinins are autoantibodies (typically IgM) that are able to agglutinate red blood cells (RBCs) at an
optimum temperature of 3-4°C, but can also react at higher temperatures, depending on the thermal amplitude.
✅ Most CAs in CAD have specificity for the I carbohydrate antigen, which is almost universally present at the RBC surface in adults and children older than age 18 months.
✅ CAD is a distinct, clonal lymphoproliferative disease with monoclonal serum immunoglobulin present in majority of cases, typically immunoglobulin M-kappa (IgMk).
✅ Clinical presentation typically includes combination of cold-induced symptoms, anemia, and hemolysis.
✅ Febrile infections, major trauma, or major surgery can result in acute exacerbation of hemolytic anemia.
✅ The diagnostic criteria for CAD include:
- Chronic hemolysis
- Positive polyspecific DAT
- Positive monospecific DAT strongly positive for C3d
- CA titer >64 at 4°C
- No overt malignant disease by clinical (and, if required, radiological) examination
✅ Treatment includes
- Nonpharmacologic management
- Clonally-directed therapies
- Rituximab monotherapy
- Rituximab and fludarabine combination therapy
- Complement modulation?