The impact Cold Agglutinin Disease (CAD) can have on patients’ lives

Current management approaches for CAD1,2

Depending on severity of the disease, patients are managed and rely on the following approaches1,2:

Icon representing cold avoidance which is one nonspecific treatment approach to CAD


Icon representing crisis intervention for patients with severe anemia


Icon representing pharmacotherapy


*Avoid triggering temperatures to relieve symptoms.

Transfusions and/or plasmapheresis, which are often required to stabilize patients with severe anemia.

Pharmacotherapies have been used based on evidence of efficacy from limited clinical studies and single- or pooled-case reports.

Despite cold avoidance and other therapies, many patients remain in a hemolytic state over 5 years3


Chart depicting LDH levels were elevated consistently over 5 years even with nonspecific approaches


Chart depicting bilirubin levels were elevated consistently over 5 years even with nonspecific approaches


Chart depicting hemoglobin levels were elevated consistently over 5 years even with nonspecific approaches

Data from a population-based retrospective follow-up study of Norwegian patients with CAD (n=86).

The charts above reflect mean hemolytic biomarker levels collected over 5 years. Throughout the study, for some patients there were large individual differences in regard to changes in these biomarkers.

Fatigue is among the most frequently reported symptoms for patients with CAD4

In an interview-based study of patients with CAD who, on average, were diagnosed 6 years prior (N=16):


Number of Participants

CAD Fatigue Chart
  • Fatigue/
    lack of energy
  • Reaction
    to cold
  • Shortness
    of breath
  • Trouble with
  • Sleep
  • Spontaneous
  • Probed
81.3% reported giving up/limiting enjoyable activities due to CAD-related symptoms


reported giving up/limiting enjoyable activities due to CAD-related symptoms (eg, discontinuing outdoor activities, restricting travel)

Study limitations include small sample size, race (all participants were white and non-Hispanic; however, the sample was geographically diverse), and that previous CAD treatment was not systematically collected for all subjects.

*Reactions to cold environments included cold or numb feet, hands, or other body parts; skin discoloration; muscle aches or headaches; and fatigue.

Sleep disturbances included problems falling asleep or staying asleep.

Study sponsored by Sanofi.

Hear from Fred,

a patient living with CAD, about the struggles he's faced due to his diagnosis.

When they said I was primary CAD, cold agglutinin, my first reaction is, “Okay, what is it?” and second reaction is “Well, let’s fix it,” and unfortunately the doctors all say exactly the same thing, “There’s nothing we can do for you, there’s no cure for it,” and it’s very cavalier the way they say, “Don’t get cold.” “Don’t get cold” is a very easy thing for people to say, and it’s easy for people to deal with, but when you have this disease it’s not so easy to deal with because cold can happen at any point in time. Coming out of the shower, just that temperature change from your body being wet to a cooler environment can trigger problems, right? Going in a heated swimming pool, the heated swimming pool is fine, that’s something you can deal with. It’s coming out of the swimming pool that is where the change, that temperature change, and it is that minor of a change, right? There’s a lot of precautions that we now have to take in our lives, which changed our lives. It changes all the time, right? That’s the whole thing with it is we may be used to something this year, next year there’s probably going to be something different. This is a journey that is uncertain and is always uncertain, and it never, it never really nails itself down because it changes all the time, right? So psychologically, you have high days and you have low days, and absolutely I went through depression and anger and the whole gamut of emotions for it. Now I’ve gotten to the point and I’m at a good point in my life where I’ve accepted it now, and now it’s just my day-to-day changes and it’s just you adapt to that, but psychologically it’s hard to deal with because most people will look at you and say, “Well, you look fine. You look fine,” and when people say that, it’s “Well, yeah, I look fine but inside I’m not; it’s the inside part that is not working properly.” And that’s part of the battle, too, is because everybody that you meet says, “Well, you don’t look sick.” Well, I don’t look sick because I try and keep myself healthy and all the rest, right? But yeah, it’s a hard journey and I’m not going to deny that it’s not but, like I said, to me, this is probably one of the hardest things I’ve ever done in my life–is to deal with this day-to-day.

Icon of vein representing CAD risk

CAD can have
serious consequences

Icon of checklist

Understand criteria
to diagnose CAD
in patients

CAD=Cold Agglutinin Disease; 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, 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 3. 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. 4. Su J, Kosa K, DiBenedetti D. Patient-reported disease burden. Poster presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; Virtual conference. Poster 2484.