Modelization of Blood-Borne Hypercoagulability in Myeloma: A Tissue-Factor-Bearing Microparticle-Driven Process
Loula Papageorgiou1,2, Kutaiba Alhaj Hussen2,3, Sandrine Thouroude1
1Research 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.
TH Open : Companion Journal to Thrombosis and Haemostasis
|November 7, 2019
Summary
Multiple myeloma plasma cells (MPCs) release microparticles rich in tissue factor (TF), significantly increasing thrombin generation and contributing to hypercoagulability in patients.
Area of Science:
- Hematology
- Oncology
- Biochemistry
Background:
- Hypercoagulability is a frequent finding in newly diagnosed multiple myeloma patients.
- Cancer cells, particularly through tissue factor (TF) expression, are known to promote coagulation.
- Mechanisms of coagulation activation by myeloma plasma cells (MPCs) remain under-investigated.
Purpose of the Study:
- To identify key factors released by MPCs that enhance thrombin generation (TG).
Main Methods:
- Analyzed TF and annexin V expression on MPCs and MPC-derived microparticles (MPC-dMPs) via flow cytometry.
- Quantified TF activity (TFa) and TF gene expression.
- Assessed TG using calibrated automated thrombogram (CAT) assay in various plasma conditions.
Main Results:
- MPC-dMPs exhibited twofold higher TF levels and significantly greater TFa than MPCs.
- Both MPCs and MPC-dMPs augmented TG in human plasma.
- TG was markedly higher in the presence of MPC-dMPs compared to MPCs.
Conclusions:
- MPCs induce hypercoagulability indirectly via TF-rich MPC-dMPs.
- Low TFa from MPCs suggests MPC-dMPs are the primary drivers of hypercoagulability in the myeloma microenvironment.
