Patients with primary immune thrombocytopenia (ITP) and high levels of complement biomarkers may have a worse response to treatment with thrombopoietin receptor agonists (TPO-RAs), according to a study published in Platelets.

During the study, patients with primary ITP with significantly elevated baseline levels of soluble terminal complement complexes (sTCC) tended to have an inadequate platelet response. They did not have a significant platelet count increase during the treatment period with an aggregate change in platelet counts of only 17 x 109/L compared to 95 x 109/L in patients with ITP with normal baseline sTCC levels. Patients with high sTCC also tended to require rescue therapy with intravenous immunoglobulin during the study.

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Plasma levels of the complement degradation product C4d could be used to distinguish between patients with normal levels of sTCC (sTCC-normal) at baseline and those with elevated sTCC levels (sTCC-high). The C4d levels were higher in the sTCC-high group at baseline and week 1 but quickly declined. Intergroup differences were insignificant starting at week 2 of treatment even though C4d levels still tended to be higher in the sTCC-high group until week 12.

“For the first time, an inverse relationship was prospectively shown between biomarkers of complement activation and the platelet response during TPO-RA therapy in a small cohort of patients with primary ITP,” the authors said.

“The implementation of routine complement testing in patients with primary ITP may prove clinically valuable as a subset of patients with difficult or refractory disease could benefit from complement-targeted therapeutics,” the authors suggested.

A total of 15 patients with ITP and 14 healthy controls were enrolled during the study. The median age at study enrollment was 61 years and no significant difference in baseline concentrations of sTCC and C4d were observed between the 2 cohorts. Using baseline values of the healthy controls, an sTCC cutoff of greater than .11 mg/L was used to distinguish patients with ITP with normal levels (n=10) vs high levels of sTCC (n=5).


Åkesson A, Bussel JB, Martin M, et al. Complement activation negatively affects the platelet response to thrombopoietin receptor agonists in patients with immune thrombocytopenia: a prospective cohort study. Platelets. Published online January 13, 2023. doi:10.1080/09537104.2022.2159019