RECOGNISING CAD
DIAGNOSING CAD
MANAGING CAD

Recognising CAD early can help patients receive optimal care1

CAD is a rare, chronic, autoimmune haemolytic anaemia that shouldn’t be confused with CAS secondary to infection or cancer

Unlike CAS, CAD is not secondary to overt malignancy or an acute infection2,3

CAD icon

  • Chronic cold agglutinin-mediated AIHA*

  • Classical pathway complement-mediated haemolysis

  • Formerly known as primary CAD

CAS icon
  • Cold agglutinin-mediated AIHA secondary to an underlying condition, for example, infections (Mycoplasma pneumoniae or Epstein-Barr virus), rheumatological disorders or overt malignancies
  • Formerly known as secondary CAD

Recognising the clinical manifestations of CAD4-10

C1 activation icon

DUE TO C1 ACTIVATION

  • Chronic haemolysis (destruction of RBCs)
  • Anaemia, shortness of breath
  • Profound fatigue
  • Haemoglobinuria
  • Jaundice
Agglutination icon

DUE TO COLD-INDUCED AGGLUTINATION

  • Circulatory symptoms
    – Acrocyanosis
    – Raynaud’s phenomenon
  • Livedo reticularis (rarely)

For patients, CAD is not a benign condition

Confirming a CAD diagnosis2,3,9,11

If CAD is suspected, the test procedure requires the blood sample be kept at 37 °C to 38 °C from the time it is drawn until it is tested to avoid potential false negatives. Refrigeration must be avoided

CAD diagnosis image

C1-activated haemolysis and other consequences are not adequately addressed by current management approaches3,7,11

Current management approaches include cold avoidance, unapproved pharmacotherapies and crisis intervention

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COLD AVOIDANCE

Cold avoidance icon

Supportive care with cold avoidance alone often isn’t enough

82%

of patients needed unapproved
pharmacotherapies to manage CAD†

UNAPPROVED PHARMACOTHERAPIES

Clipboard icon

Patients with CAD receive multiple types of unapproved pharmacotherapies

3.5

different types, on average‡

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CRISIS INTERVENTION

Transfusion icon

Crisis intervention benefit is short lived and inconsistent

2

key strategies:
• Transfusions
• Plasmapheresis (rare)

Future goals icon

See the goals for future CAD treatment

Patient burden icon

CAD can impact patients’ lives

AIHA=autoimmune haemolytic anaemia; CAS=cold agglutinin syndrome; DAT=direct antiglobulin test; RBC=red blood cell.

*Patients may have a B-cell lymphoproliferative disorder detectable in blood or marrow but no clinical or radiological evidence of malignancy.
†Data from a retrospective analysis of patients with confirmed CAD (n=89).
‡Data collected from 21 patients who received treatment in a retrospective review of a healthcare database.

References: 1. 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 2. Jäger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the First International Consensus Meeting. Blood Rev. 2020;41:100648. doi:10.1016/j.blre.2019.100648 3. Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26(3):107-115. doi:10.1016/j.blre.2012.01.002 4. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. Semin Hematol. 2018;55(3):141-149. doi:10.1053/j.seminhematol.2018.04.002 5. Berentsen S, Röth A, Randen U, Jilma B, Tjønnfjord GE. Cold agglutinin disease: current challenges and future prospects. J Blood Med. 2019;10:93‐103. doi:10.2147/JBM.S177621 6. Elharake M, Bors K. Cold agglutinin disease: a case report. W V Med J. 2017;1-4. 7. 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 8. Berentsen S, Randen U, Tjønnfjord GE. Cold agglutinin-mediated autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2015;29(3):455-471. doi:10.1016/j.hoc.2015.01.002 9. 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 10. Aljubran SA. Cold agglutinin disease clinical presentation. Medscape website. Updated December 2, 2020. Accessed March 30, 2022. emedicine.medscape.com/article/135327-clinical 11. Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013;122(7):1114-1121. doi:10.1182/blood-2013-02-474437

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