Frequently Asked Questions

What tests confirm Cold Agglutinin Disease?

Most patients are diagnosed with CAD through a positive direct antiglobulin test (DAT) and detectable presence of IgM autoantibody.1,2

  • If CAD is suspected based on initial anemia presentation, first confirm hemolysis is present via bilirubin and LDH blood tests
  • Then, confirm polyspecific DAT and monospecific DAT for C3d
  • Perform a full clinical assessment to rule out possible alternative causes for hemolytic anemia and positive DAT
  • Next, confirm that Cold Agglutinin Titer is above or equal to 1:64
  • Evaluate with further clinical and serological assessments to confirm diagnosis of CAD
  • To distinguish CAD from CAS, confirm no infection or overt malignancy
  • If no infection or overt malignancy is present, diagnose with CAD
  • If overt malignancy is present, diagnose with CAS
  • If febrile infection is present, determine if onset of anemia occurred before infection. If so, diagnose with CAD; if not, diagnose with CAS
CAD=Cold Agglutinin Disease; CAS=Cold Agglutinin Syndrome; IgM=immunoglobulin M; LDH=lactate dehydrogenase.
References: 1. Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26(3):107-115. 2. Hill QA, Stamps R, Massey E, et al; on behalf of the British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017;176(3):395-411.