Frequently Asked Questions

How do I diagnose Cold Agglutinin Disease?

Cold Agglutinin Disease (CAD) is a rare and serious autoimmune hemolytic condition with systemic acute and chronic consequences.1-3 Because of the risks patients with CAD face, it's important to understand how to accurately diagnose CAD.

Diagnosis of CAD requires both a positive direct antiglobulin test (DAT) and detectable presence of IgM autoantibodies.4,5

  • 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 between CAD and CAS, confirm presence of infection or overt malignancy
  • If no infection or overt malignancy, 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, then diagnose with CAD; if not, diagnose with CAS

Find out more about CAD diagnosis here.

CAD=Cold Agglutinin Disease; CAS=cold agglutinin syndrome; DAT=direct antiglobulin test; IgM=immunoglobulin M; LDH=lactate dehydrogenase.
References: 1. Mullins M, Jiang X, Bylsma LC, et al. Cold agglutinin disease burden: a longitudinal analysis of anemia, medications, transfusions, and health care utilization. Blood Adv. 2017;1(13):839-848. doi:10.1182/bloodadvances.2017004390 2. Berentsen S, Beiske K, Tjønnfjord GE. Primary chronic cold agglutinin disease: an update on pathogenesis, clinical features and therapy. Hematology. 2007;12(5):361-370. doi:10.1080/10245330701445392 3. Broome CM, Cunningham JM, Mullins M, et al. Increased risk of thrombotic events in cold agglutinin disease: a 10‐year retrospective analysis. Res Pract Thromb Haemost. 2020;4(4):628-635. doi:10.1002/rth2.12333 4. Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26(3):107-115. 5. Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A; British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017;176(3):395-411. doi:10.1111/bjh.14478