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. 2022 Jan;62(1):51-59.
doi: 10.1111/trf.16745. Epub 2021 Nov 23.

Complement-mediated hemolysis persists year round in patients with cold agglutinin disease

Alexander Röth  1 , Jon Fryzek  2 , Xiaohui Jiang  3 , Heidi Reichert  3 , Parija Patel  4 , Jun Su  4 , Jaime Morales Arias  4 , Catherine M Broome  5
Affiliations

Complement-mediated hemolysis persists year round in patients with cold agglutinin disease

Alexander Röth et al. Transfusion. 2022 Jan.

Abstract

Background: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by immunoglobulin M autoantibodies that bind to the "I" antigen on erythrocytes. IgM binding results in either agglutination at ≤37°C, activation of the classical complement pathway, or both. Patients with CAD can have transient agglutination-mediated circulatory symptoms triggered by exposure to cold conditions. Separately, patients with CAD can experience complement-mediated symptoms such as anemia, hemolysis, and fatigue, but the effect of the season on these complement-mediated manifestations of CAD and clinical outcomes is not well understood.

Methods: Using data from the Optum® de-identified Electronic Health Record dataset, we compared hemoglobin, markers of hemolysis (bilirubin and lactate dehydrogenase [LDH]), and healthcare resource utilization (HRU) between seasons for 594 patients (62% female; 66% aged ≥65 years) with CAD (defined as having CAD-related terms in their clinical notes on ≥3 separate occasions between December 2008 and May 2016). Laboratory parameters and HRU were compared between seasons using multivariate regression models.

Results: Estimated median hemoglobin (9.87 g/dL in summer and 9.86 g/dL in winter; P = 0.944) and bilirubin (1.04 mg/dL in summer and 1.09 mg/dL in winter; P = 0.257) were similar in winter versus summer. While LDH was statistically significantly higher in winter compared with summer (P < 0.001), the estimated median value was above normal for both seasons (309 U/L in summer and 367 U/L in winter). HRU measures and transfusion and thromboembolism rates were similar across seasons.

Conclusions: Patients with CAD had evidence of persistent chronic hemolysis, HRU, and thromboembolism risk year round.

Keywords: anemia; epidemiology; immune hemolytic anemia; thrombosis.

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References

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