Serum Complement Levels in Immune Thrombocytopenia: Characterization and Relation to Clinical Features

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.1087-1087
• Main Authors: Cheloff, Abraham Z, Kuter, David J., Al-Samkari, Hanny
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-125341

Introduction: Complement activation contributes to platelet destruction in immune thrombocytopenia (ITP). Autoantibodies bound to platelets fix complement (Naiaoui et al. 2011) and ITP platelets have increased cell surface-bound C3 and C4 (Kurata et al. 1985). Despite this known pathophysiology there is very little published data describing serum complement levels in ITP patients and no data describing a possible relation of complement levels to disease characteristics. Therapeutics targeting the complement system are now emerging for the treatment of ITP, including an ongoing clinical trial of the C1 esterase inhibitor sutimlimab (BIVV009). ITP patients with major complement-mediated platelet destruction as revealed by low serum complement levels may be more likely to respond to anti-complement therapies. With this background, we aimed to characterize the serum complement levels of C3, C4, and total hemolytic complement (CH50) in a large cohort of ITP patients and explore the relation of these levels to clinical features in 108 adults with ITP. Complement measurements from 120 healthy adult subjects were used for comparison. ITP patient data was collected retrospectively as standard clinical serum complement evaluation has been a routine part of initial patient evaluation at our ITP center for the past two years. Methods: Serum C3, C4, and CH50 were measured using a commercially-available turbidimetric assay (Optilite System, Binding Site, Birmingham, UK). Reference ranges were: C3, 81.1-157.0 mg/dL; C4, 12.9-39.2 mg/dL; CH50, 41.7-95.1 U/mL. Data collected for analysis included dates and results of complement testing (including disease status and platelet count at time of testing), patient demographics, and disease characteristics. Satisfaction of the 2011 American Society of Hematology (ASH) ITP diagnostic criteria were required for ITP patient inclusion and ASH ITP guideline definitions of disease severity and treatment response were used. Patients with other disorders known to reduce complement (e.g. systemic lupus) were excluded. Wilcoxon rank-sum tests and t-tests were used to compare groups. Multivariate logistic regression was used to model the probability of low complement levels based on disease severity and platelet count as well as model the probability of treatment response based on complement levels. Results: A total of 98 C3 assays, 97 C4 assays, and 102 CH50 assays from 108 ITP patients (92 patients had all three assays performed) were col