OC 33.5 - Platelet function and molecular characteristics of essential thrombocythemia and reactive thrombocytosis

Background: Thrombocytosis is commonly encountered in clinical practice as a secondary process of infection, surgery, and iron-deficiency anemia (reactive thrombocytosis), or a major phenotype of myeloproliferative neoplasms such as essential thrombocythemia characterized by an increased risk of thrombo-hemorrhagic complications.

Aims: The aim of this study was to evaluate platelet function and identify molecular characteristics in patients with essential thrombocythemia and reactive thrombocytosis.

Methods: We collected samples from 12 patients (7 with essential thrombocythemia and 5 with reactive thrombocytosis) and 5 healthy controls. None of the patients was under antiplatelet or cytoreductive therapy. We performed platelet aggregation tests induced by several different agonists and flow cytometry studies to analyze platelet function in both patient and control groups. Washed and isolated platelets were prepared for proteomic analysis.

Results: We observed defective responses to different agonists during platelet aggregation tests in patients with essential thrombocythemia and reactive thrombocytosis compared with healthy controls (Fig.1A). In the additional assay by flow cytometry, the platelets from patients with essential thrombocythemia showed a lower expression of activation markers after stimulation (Fig.1B). These results suggested impaired platelet function in patient groups. Proteomic analysis revealed potential molecular basis of platelet dysfunction. In reactive thrombocytosis group, hundreds of proteins associated with blood microparticle and extracellular region had down-regulated expressions and enrichment analysis indicated a significant defect in complement and coagulation cascade pathways (Fig.2A-C). In essential thrombocythemia group, the protein expression profiles showed higher heterogeneity among different individuals and enrichment analysis suggested additional abnormalities of plasma membrane and organelles (Fig.2D-E).

Conclusion(s): Understanding the distinction between essential thrombocythemia and reactive thrombocytosis may play an important role in improving treatment planning and evaluating prognosis of diseases.