Publications : 2022

Broome CM, Hooda N, Su J, Jiang X, Nicholson G, Frankenfeld CL, Iglesias-Rodriguez M, Fryzek J, Patel Parija. 2022. Medically-attended anxiety and depression is increased among newly diagnosed patients with cold agglutinin disease: Analysis of an integrated claim-clinical cohort in the United States. PLOS ONE open access,



Cold agglutinin disease (CAD) is a rare, chronic form of autoimmune hemolytic anemia. Clinical manifestations can include classical complement pathway-mediated chronic hemolysis, anemia, and profound fatigue. Research has shown that patients with other anemias may develop anxiety and depression, but this has not been studied previously in patients with CAD.


CAD patients were identified in the Optum Claims-Clinical dataset (between January 1, 2006–June 30, 2016) and matched to comparison patients without CAD by patient factors. Adjusted Cox regression models estimated time to anxiety and depression, defined by three different outcomes: medication use, hospitalization, and therapy related to anxiety and depression. Subset analyses were performed for primary CAD. Patients were followed until they had anxiety and depression, they left the Optum system, death, or the study period ended (June 30, 2016).


Patients with CAD (n = 384) were more likely to have medically attended anxiety and depression (adjusted hazard ratio [aHR]: 1.6; 95% confidence interval [CI]: 1.3–2.1), to be prescribed antidepressants or psychotherapy after their CAD diagnosis (aHR: 1.8; 95% CI: 1.2–2.9), or to be hospitalized for an anxiety and depression-related event along with medication or psychotherapy (aHR: 2.0; 95% CI: 1.4–2.9) relative to matched comparisons (n = 2789), during the follow-up period. Patients with primary CAD were at increased risk for medically attended anxiety and depression (aHR: 1.8; 95% CI: 1.4–2.4), with the highest risk for prescription medication or therapy (aHR: 2.7; 95% CI: 1.6–4.6).


Our study indicates that medically attended anxiety and depression manifest at a higher rate in CAD patients than in a matched non-CAD cohort. Study findings suggest that CAD patients may experience a greater burden on mental health that may negatively contribute to their overall quality of life. Further investigation on this topic is warranted.