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.
Highlights
Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma
The TF activity (TFa) expressed by myeloma plasma cells (MPCs)-dMPs was significantly higher compared with that expressed by MPCs
The TFa expressed by MPC-dMPs (26.2 nM) was significantly higher as compared with that expressed by MPCs at the count of 1,000 cells/μL (11.95 Æ 1.9 and 6.07 Æ 0.4 ng/mL, respectively; p < 0.05; ►Fig. 3)
Summary
Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. Multiple myeloma is a plasma cell malignancy characterized by bone marrow infiltration leading to multiple lytic bone lesions, renal failure, anemia, and increased risk of venous thromboembolism.[1] Newly diagnosed, chemotherapy naïve patients with multiple myeloma present high levels of procoagulant phospholipids in plasma along with an increased concentration of biomarkers which indicate activation of blood coagulation and endothelial cells.[2]. The identification of the procoagulant potential of cancer cells, principally mediated from tissue factor (TF), attracts particular interest since it is closely related with cancer aggressiveness, proangiogenic properties, resistance to anticancer treatment, and metastatic potential.[3] Enhanced fibrin formation as well as clots with low permeability and resistant to lysis have been observed in patients with multiple myeloma.[4] Myeloma plasma cells (MPCs) are potential initiators of the process leading to hypercoagulability. Fibrin together with activated platelets may either act as a shield of cancer cells against the access of anticancer drugs or alter the efficiency of the immunosurveillance system.[5,6,7,8,9]
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