What isCold Agglutinin Disease (CAD)?

CAD is a rare autoimmune hemolytic condition with potentially serious acute and chronic consequences that are driven by C1 activation of the classical complement pathway1

Unlike Cold Agglutinin Syndrome, Cold Agglutinin Disease is not secondary to cancer or an acute infection2


Solid colored circle with the letters CAD in the middle
  • CAD is also known as primary CAD
  • Chronic autoimmune hemolytic anemia
  • Classical complement-dependent hemolysis


Circle with the letters CAS in the middle
  • CAS is also known as secondary CAD
  • Chronic autoimmune hemolytic anemia secondary to overt malignant disease
  • OR
  • Acute infection

Understanding the CAD patient population

Icon of pie chart with 20% highlighted

20% of all autoimmune hemolytic anemias are CAD3

Icon of a globe

Up to 16 people per 1,000,000 are impacted by CAD4

58 years

Average age of onset is approximately 60 years, but CAD has been seen in some patients as young as 30 years4

Hear from Brad,

a patient with CAD, as he discusses his path to diagnosis, the impact CAD has on his daily life, and the challenges he's faced because of his disease.

My name's Brad, I have primary CAD, Cold Agglutinin. I first started noticing symptoms of Cold Agglutinin—I didn't know it was Cold Agglutinin at the time—and I was a rescue specialist so we were out at sea and we went on a search and rescue call and we were pulling in the lines and my hands got so cold that it felt...it would have been more comfortable if somebody cut my fingers off. And after that trip, that call we did, I was just absolutely exhausted. I just had no energy, and I literally took the day off of work. So I went from 2011 to 2013 with just a barrage of tests. I have done 2 bone marrow, dozens and dozens of vials of blood, CT scans, MRIs; and in 2013, that's when I was diagnosed with primary CAD. I have had 2 strokes, minor strokes for me, which is very lucky. Being tired is one thing, being fatigued is taking tired 10 steps forward above that. Fatigue is something where you don't even want to get up out of bed, the fatigue is so much. If you were dragged behind a tractor and couldn't get up, that's the fatigue that we feel. That's how hard it is some days. This process goes on for years and years and years—this process will go on for the rest of my life, and that's where we need to educate people that this is not just a turn-on and turn-off situation. This will be with me for the rest of my life.

CAD can be more severe than previously believed3,5

The disease course is unpredictable with events varying in frequency and severity

Circles depicting possible events for patients with CAD


The most common symptoms of CAD are hemolytic anemia, debilitating fatigue, and circulatory symptoms.

Recognize the signs and symptoms of CAD3,6,7

Icon of blood representing CAD symptom of hemolytic anemia


Icon of person hunched over representing CAD symptom of debilitating fatigue


Icon of lung representing CAD symptom of shortness of breath

of breath

Icon of hand representing CAD symptom of bluing or purpling of hands and feet


Icon of eye representing CAD symptom of jaundice


Icon of bottle representing CAD symptom of dark urine


Icon of vein representing CAD risk

CAD can have
serious consequences

Icon of blood representing CAD symptom of hemolytic anemia

The complement
pathway plays a
critical role in CAD

CAD=Cold Agglutinin Disease; CAS=Cold Agglutinin Syndrome.
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. 2. Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012;26(3):107-115. 3. 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. 4. Berentsen S, Ulvestad E, Langholm R, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica. 2006;91(4):460-466. 5. Broome CM, Cunningham JM, Mullins M, et al. Incidence of thromboembolic events is increased in a retrospective analysis of a large cold agglutinin disease (CAD) cohort. Poster presented at: 59th Annual Meeting and Exposition of the American Society of Hematology Conference (ASH); December 9-12, 2017; Atlanta, GA. Abstract 928. 6. 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. 7. Aljubran SA. Cold agglutinin disease clinical presentation. Medscape website. emedicine.medscape.com/article/135327-clinical. Updated August 28, 2018. Accessed April 19, 2019.