Cold Agglutinin Disease (CAD)

CAD is a debilitating autoimmune hemolytic anemia in which autoantibodies activate Complement, leading to the destruction of red blood cells


Median age at symptom onset is 65 years, median age at diagnosis is 72 years.

Primary CAD Overview


  • Crippling fatigue correlated with low hemoglobin
  • 44% of these patients are severely anemic at disease onset2
  • Severe CAD patients can require intensive disease management and dependency on frequent blood transfusions
  • Severe CAD patients have an increased risk of potentially fatal hemolytic crises or thrombotic events

Treatment Options


  • Some patients may only experience mild anemia, managed by avoiding acute exposure to cold. Most patients require treatment. There are no FDA- or EMA-approved medications for CAD
  • Most patients treated with immunotoxic therapy do not have a complete response. For those that do respond, the time to achieve a response can take several months and most patients relapse with no alternative treatment options
  • Significant unmet need exists for an approved, safe, and fast-acting therapy that can normalize hemoglobin and remove the dependence upon transfusions

Disease Mechanism

CAD is characterized by the presence of autoantibodies called cold agglutinins that bind to a specific cell surface protein on red blood cells. Cold agglutinins are potent activators of the Classical Complement Pathway, leading to deposition of C3b on red blood cells. These C3b-coated red blood cells are phagocytosed in the liver causing extravascular hemolysis, the primary driver of anemia in CAD patients.


The COMPASS Registry

True North sponsors a patient registry for Cold Agglutinin Disease and other autoimmune hemolytic anemias–dedicated to advancing a deeper understanding of these diseases, engaging with patients, and supporting clinical trial recruitment.


  1. Berentsen et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica January 2006 91: 460-466.
  2. Barcellini et al. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood. 2014 Nov 6;124(19):2930-6.