Hemostatic changes by thrombopoietin-receptor agonists in immune thrombocytopenia patients

Blood Rev. 2021 May:47:100774. doi: 10.1016/j.blre.2020.100774. Epub 2020 Nov 10.

Abstract

Thrombopoietin receptor agonist (TPO-RA) treatment increases the thrombosis rate in immune thrombocytopenia (ITP). We hypothesize that TPO-RAs influence platelet function, global and secondary hemostasis and/or fibrinolysis. A systematic review was performed. If possible, data were compared between responders (relevant increase in platelet count), and non-responders. Twelve observational studies with 305 patients were included (responders (127/150 (85%))). There were indications that TPO-RA treatment enhanced platelet function, with respect to platelet-monocyte aggregates, soluble P-selectin, GPVI expression, and adhesion under flow. Studies addressing global and secondary hemostasis and fibrinolysis were scarce. Overall, no changes were found during TPO-RA treatment, apart from an accelerated clot formation and conflicting data on levels of plasminogen activator inhibitor (PAI)-1. The parameters that increased have previously been associated with thrombosis in other patient groups, and might contribute to the increased rate of thrombosis observed in TPO-RA-treated ITP patients.

Keywords: Hemostasis; ITP; Immune thrombocytopenia; Platelet activation; Platelet function; Thrombopoietin receptor agonists.

Publication types

  • Review

MeSH terms

  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Fibrinolysis / drug effects
  • Gene Expression Regulation / drug effects
  • Hemostatics / adverse effects
  • Hemostatics / therapeutic use*
  • Humans
  • Monocytes / metabolism
  • Monocytes / pathology
  • P-Selectin / biosynthesis
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Platelet Aggregation / drug effects*
  • Platelet Membrane Glycoproteins / biosynthesis
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / metabolism
  • Purpura, Thrombocytopenic, Idiopathic* / pathology
  • Receptors, Thrombopoietin / agonists*
  • Receptors, Thrombopoietin / metabolism
  • Thrombosis / chemically induced
  • Thrombosis / metabolism
  • Thrombosis / pathology

Substances

  • Hemostatics
  • P-Selectin
  • Plasminogen Activator Inhibitor 1
  • Platelet Membrane Glycoproteins
  • Receptors, Thrombopoietin
  • SELP protein, human
  • SERPINE1 protein, human
  • platelet membrane glycoprotein VI
  • MPL protein, human