Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features

Abstract

Background Complement may contribute to platelet destruction in immune thrombocytopenia (ITP), but serum complement levels of ITP patients are not well defined. This study characterized C3, C4, and CH50 levels from 108 ITP patients in comparison with 120 healthy subjects. Methods Results of complement testing performed using commercially available turbidimetric immunoassays were retrospectively analyzed. Mean complement levels in patients with ITP were compared with levels from a sample of 120 healthy subjects, and subgroups of ITP patients were compared. Regression analyses evaluated for relations between low complement levels and disease severity and response to ITP treatments. Results One hundred eight patients with ITP were included. Mean C3, C4, and CH50 were significantly lower in patients with ITP compared with healthy subjects, largely driven by the 32% of patients with ITP with substantial reductions in one or more assays. Patients requiring treatment had lower mean C4 (18.1 vs 23.1 mg/dL; P = .042) and CH50 (50.4 vs 63.0 mg/dL; P = .004). Mean C3 was higher in splenectomized versus nonsplenectomized patients (120.6 vs 101.0 mg/dL; P = .035). In multivariable analyses, reduced complement did not predict treatment response to corticosteroids, intravenous immunoglobulin, or thrombopoietin receptor agonists but low C4 levels did predict more severe ITP (relative to nonsevere disease, odds ratio for severe/refractory disease: 6.28; 95% confidence interval, 0.75‐52.54; P = .090). Complement levels in patients with ITP were generally consistent over repeat measurements. Conclusions Complement levels are reduced in one‐third of patients with ITP and are associated with more severe disease. Additional study is needed to evaluate if hypocomplementemia is predictive of response to emerging complement‐directed therapies.

Recent advances in the mechanisms and treatment of immune thrombocytopenia

“…In spite of this, however, therapeutics targeting complement such as the C1 esterase inhibitor sutimlimab are currently being studied in the treatment of ITP. 34,35…”

Emerging Therapies in Immune Thrombocytopenia

“…Complement deposition is observed at the platelet surface in more than a half of ITP patients [ 80 , 81 ], and about 30% of ITP patients have at least one complement exploration (C3, C4 or CH50) below the lower range [ 82 ]. Moreover, complement activation correlates with disease activity, being higher in patients with an active disease compared to those in partial or complete response [ 83 ].…”

Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

“…Immune thrombocytopenia (ITP) results from autoimmune destruction of platelets in the reticuloendothelial system due to platelet autoantibodies and other immune mechanisms, resulting in increased platelet turnover as well as inadequate platelet production. [1][2][3][4][5] Primary ITP is defined as an isolated thrombocytopenia <100 × 10 9 / L in the absence of other causes or disorders that may be associated with thrombocytopenia, as distinguished from secondary ITP, which is associated with other conditions such as infections, drug effects, rheumatological diseases, or lymphoproliferative disorders. 6,7 The incidence of ITP in the US population is approximately 6.1 per 100,000 persons per year, or 13.7 per 100,000 persons per year in those 65 years or greater, and results in significant economic burden.…”