Modelization of Blood-Borne Hypercoagulability in Myeloma: A Tissue-Factor-Bearing Microparticle-Driven Process
Loula Papageorgiou,
Kutaiba Alhaj Hussen,
Sandrine Thouroude,
Elisabeth Mbemba,
Héléne Cost,
Laurent Garderet,
Ismail Elalamy,
Annette Larsen,
Patrick Van Dreden,
Meletios A. Dimopoulos,
Mohamad Mohty,
Grigoris T. Gerotziafas
Affiliations
Loula Papageorgiou
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
Kutaiba Alhaj Hussen
Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France
Sandrine Thouroude
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
Elisabeth Mbemba
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
Héléne Cost
Clinical Research, Diagnostica Stago, Gennevilliers, France
Laurent Garderet
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
Ismail Elalamy
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
Annette Larsen
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
Patrick Van Dreden
Clinical Research, Diagnostica Stago, Gennevilliers, France
Meletios A. Dimopoulos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Mohamad Mohty
Department of Hematology and Cell Therapy, Saint Antoine Hospital, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Sorbonne University, Paris, France
Grigoris T. Gerotziafas
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
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.
