Complement-mediated hemolysis persists year round in patients with cold agglutinin disease. 2022

Alexander Röth, and Jon Fryzek, and Xiaohui Jiang, and Heidi Reichert, and Parija Patel, and Jun Su, and Jaime Morales Arias, and Catherine M Broome
Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

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

UI MeSH Term Description Entries
D007770 L-Lactate Dehydrogenase A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D008297 Male Males
D003165 Complement System Proteins Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY). Complement Proteins,Complement,Complement Protein,Hemolytic Complement,Complement, Hemolytic,Protein, Complement,Proteins, Complement,Proteins, Complement System
D005260 Female Females
D006461 Hemolysis The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. Haemolysis,Extravascular Hemolysis,Intravascular Hemolysis,Extravascular Hemolyses,Haemolyses,Hemolyses, Extravascular,Hemolyses, Intravascular,Hemolysis, Extravascular,Hemolysis, Intravascular,Intravascular Hemolyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000744 Anemia, Hemolytic, Autoimmune Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS. Anemia, Hemolytic, Idiopathic Acquired,Autoimmune Haemolytic Anaemia,Autoimmune Hemolytic Anemia,Cold Agglutinin Disease,Hemolytic Anemia, Autoimmune,Acquired Autoimmune Hemolytic Anemia,Anemia, Hemolytic, Cold Antibody,Cold Antibody Disease,Cold Antibody Hemolytic Anemia,Idiopathic Autoimmune Hemolytic Anemia,Agglutinin Disease, Cold,Anaemia, Autoimmune Haemolytic,Anemia, Autoimmune Hemolytic,Autoimmune Haemolytic Anaemias,Autoimmune Hemolytic Anemias,Cold Agglutinin Diseases,Cold Antibody Diseases,Haemolytic Anaemia, Autoimmune
D001663 Bilirubin A bile pigment that is a degradation product of HEME. Bilirubin IX alpha,Bilirubin, (15E)-Isomer,Bilirubin, (4E)-Isomer,Bilirubin, (4E,15E)-Isomer,Bilirubin, Calcium Salt,Bilirubin, Disodium Salt,Bilirubin, Monosodium Salt,Calcium Bilirubinate,Hematoidin,delta-Bilirubin,Bilirubinate, Calcium,Calcium Salt Bilirubin,Disodium Salt Bilirubin,Monosodium Salt Bilirubin,Salt Bilirubin, Calcium,delta Bilirubin
D013923 Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream. Thromboembolisms

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