PB2300: COMPLEMENT ACTIVATION NEGATIVELY AFFECTS THE PLATELET RESPONSE TO THROMBOPOIETIN RECEPTOR AGONISTS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: A PROSPECTIVE COHORT STUDY

Abstract

Background: Increased platelet destruction is central in the pathogenesis of immune thrombocytopenia. However, impaired platelet production is also relevant, and its significance underlies the rationale for treatment with thrombopoietin receptor agonists (TPO-RAs). Previous studies have associated enhanced complement activation with increased disease severity. Additionally, treatment refractoriness has been demonstrated to resolve by the administration of complement-targeted therapeutics in a subset of patients. Aims: To investigate the association between complement activation and platelet response to TPO-RA therapy. Methods: In this study, blood samples from patients with chronic immune thrombocytopenia (n = 15) were prospectively collected before and 2, 6 and 12 weeks after the initiation of TPO-RA therapy. Levels of complement degradation product C4d and soluble terminal complement complexes were assessed. Results: Patients with significantly elevated baseline levels of terminal complement complexes had more often undergone splenectomy (p = .08), exhibited more often an inadequate platelet response (p = .04) and were exclusively subjected to rescue therapy with intravenous immunoglobulin (p = .02) during the study period. C4d showed a significant (p = .01) ability to distinguish samples with significant terminal complement activation, implying engagement of the classical complement pathway. Summary/Conclusion: Elevated levels of complement biomarkers were associated with a worse TPO-RA treatment response. Larger studies are needed to confirm these results. Biomarkers of complement activation may prove valuable as a prognostic tool to predict which patients that potentially could benefit from complement-inhibiting therapy in the future.