Platelet dysfunction in immune thrombocytopenia: Finding clinical subsets with platelet phenotypes

Abstract

Patients with immune thrombocytopenia (ITP) remain a challenge to diagnose, manage and predict bleeding risk. A comprehensive assessment of platelet function may aid clinical management. This study assessed platelet parameters to predict bleeding in ITP. Blood from 103 clinically annotated cases with isolated thrombocytopenia and 123 healthy donors was evaluated. In the ITP cohort, 75/110 encounters (68%) had platelet counts below 50 × 109/L. Platelet surface proteins, reticulated platelets and activation were quantified using flow cytometry. Soluble receptor fragments, citrullinated histone-DNA (CitH3-DNA) complexes and thrombopoietin (TPO) were quantified by enzyme-linked immunosorbent assay (ELISA). Whole blood clotting and platelet contribution to clot formation were evaluated using viscoelastography. Elevated levels of glycoprotein (GP) VI (p = 0.0012), Trem-like transcript-1 (TLT-1) (p = 0.0248), platelet-bound immunoglobulin (Ig) G (p < 0.0029), CitH3-DNA complexes (p = 0.0022), TPO (p < 0.0001) and reduced platelet contribution to clot formation (p < 0.0001) were observed in primary ITP patients with bleeding and bruising symptoms. A multivariable analysis revealed that measuring platelet indices strengthened a predictive bleeding model over platelet count alone (78.1% vs. 70.48%). Symptomatic ITP patients have measurable platelet dysfunction and quantifiable differences on platelet surface, increased evidence of NETosis and elevated TPO levels. Identifying biomarkers for ITP outcomes can define subsets of disease with clinical relevance.