Frequently Asked Questions

How do I diagnose 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.

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CAD=Cold Agglutinin Disease; CAS=cold agglutinin syndrome; 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. 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. 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. 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, 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.