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Modelization of Blood-Borne Hypercoagulability in Myeloma: A Tissue-Factor-Bearing Microparticle-Driven Process

Authors
  • Papageorgiou, Loula1, 2
  • Alhaj Hussen, Kutaiba2, 3
  • Thouroude, Sandrine1
  • Mbemba, Elisabeth1
  • Cost, Héléne4
  • Garderet, Laurent5
  • Elalamy, Ismail1, 2
  • Larsen, Annette1
  • Van Dreden, Patrick4
  • Dimopoulos, Meletios A.6
  • Mohty, Mohamad7
  • Gerotziafas, Grigoris T.1, 2
  • 1 Research Group “Cancer, Haemostasis and Angiogenesis,” INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Faculty of Medicine, Institut Universitaire de Cancérologie, Sorbonne Universities, Paris, France
  • 2 Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France
  • 3 INSERM U976, Université Paris-Diderot, École Pratique des Hautes Études/PSL Research University, Institut de recherche Saint-Louis, Hôpital Saint-Louis, Paris, France
  • 4 Clinical Research, Diagnostica Stago, Gennevilliers, France
  • 5 Research Group “Proliferation and Differentiation of Stem Cells” INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Faculty of Medicine, Institut Universitaire de Cancérologie, Sorbonne Universities, Paris, France
  • 6 Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • 7 Department of Hematology and Cell Therapy, Saint Antoine Hospital, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Sorbonne University, Paris, France
Type
Published Article
Journal
TH Open: Companion Journal to Thrombosis and Haemostasis
Publisher
Georg Thieme Verlag KG
Publication Date
Nov 04, 2019
Volume
3
Issue
4
Identifiers
DOI: 10.1055/s-0039-1700885
PMID: 31693008
PMCID: PMC6828570
Source
PubMed Central
Keywords
License
Green

Abstract

Introduction Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. The identification of the procoagulant potential of cancer cells, which is principally related to tissue factor (TF) expression, attracts particular interest. The mechanisms by which myeloma plasma cells (MPCs) activate blood coagulation have been poorly investigated. Aim To identify the principal actors related with MPCs that boost thrombin generation (TG). Methods TF and annexin V expression by MPCs and MPC-derived microparticles (MPC-dMPs) was analyzed by flow cytometry. TF activity (TFa) and TF gene expression were also determined. TG in the presence of MPCs or MPC-dMPs was assessed with the calibrated automated thrombogram assay (CAT) in normal human PPP and in plasma depleted of factor VII or XII. TG was also assessed in plasma spiked with MPCs and MPC-dMPs. Results MPC-dMPs expressed approximately twofold higher levels of TF as compared with MPCs. The TFa expressed by MPC-dMPs was significantly higher compared with that expressed by MPCs. MPCs and MPC-dMPs enhanced TG of human plasma. TG was significantly higher with MPC-dMPs compared with MPCs. Conclusion MPCs indirectly induce blood-borne hypercoagulability through the release of MPC-dMPs rich in TF. Since MPCs, expressing low TFa, represent a weak procoagulant stimulus, the hypercoagulability at the microenvironment could be the resultant of MPC-dMPs rich in TF.

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