title: Activation of coagulation by lenalidomide-based regimens for the treatment of multiple myeloma.
abstract: We investigated the procoagulant effects of lenalidomide (Len)-based regimens in vitro focusing on tissue factor (TF) and phosphatidylserine (PS). We examined the effects of a pharmacological concentration of Len with or without the corticosteroid dexamethasone (Dex) and the proteasome inhibitor bortezomib (Bor) using the human vascular endothelial cell line EAhy926 and the monocytic cell lines THP-1 and U937. Cell-surface procoagulant activity (PCA) was induced by Dex-containing regimens in all lines. Expression of TF antigen on the cell surface and of TF mRNA was markedly increased by Dex-containing regimens. PS exposure was increased modestly by a Len-based regimen. PS exposure was increased modestly in EAhy926 cells, and markedly increased in THP-1 and U937 cells by Bor-containing treatment. An anti-TF monoclonal antibody almost completely blocked the induced PCA. When Len is given in combination with Dex, PCA may be induced on endothelial cells and monocytes through TF expression and PS exposure.
authors.affiliation: Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Isozumi
authors.forename: Reina
authors.initials: R
authors.lastname: Arai
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Koyama
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002460:Cell Line; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
chemical_list: D001897:Boronic Acids; D010718:Phosphatidylserines; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D013925:Thromboplastin; D000077269:Lenalidomide