title: Induction therapy alters plasma fibrin clot properties in multiple myeloma patients: association with thromboembolic complications.
abstract: Induction therapy in patients with multiple myeloma increases the risk of thromboembolism. We have recently shown that multiple myeloma patients tend to form denser fibrin clots displaying poor lysability. We investigated the effect of induction therapy on fibrin clot properties in multiple myeloma patients. Ex-vivo plasma fibrin clot permeability, turbidity, susceptibility to lysis, thrombin generation, factor VIII and fibrinolytic proteins were compared in 48 multiple myeloma patients prior to and following 3 months of induction therapy, mainly with cyclophosphamide-thalidomide-dexamethasone regimen. Patients on thromboprophylaxis with aspirin or heparins were eligible. A 3-month induction therapy resulted in improved clot properties, that is higher clot permeability, compaction, shorter lag phase and higher final turbidity, along with shorter clot lysis time and higher rate of D-dimer release from fibrin clots than the baseline values. The therapy also resulted in lower thrombin generation, antiplasmin and thrombin-activatable fibrinolysis inhibitor (TAFI), but elevated factor VIII. Progressive disease was associated with lower posttreatment clot permeability and lysability. Despite thromboprophylaxis, two patients developed ischemic stroke and 10 had venous thromboembolism. They were characterized by pretreatment lower clot permeability, prolonged clot lysis time, longer lag phase, higher peak thrombin generation, TAFI and plasminogen activator inhibitor -1. Formation of denser plasma fibrin clots with reduced lysability and increased thrombin generation at baseline could predispose to thrombotic complications during induction treatment in multiple myeloma patients. We observed improved fibrin clot properties and thrombin generation in multiple myeloma patients except those with progressive disease.
authors.affiliation: aInstitute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow bDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Wroclaw cDepartment of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice d1st Department of Hematology, City Hospital, Opole eDepartment of Hematology, Medical University of Lublin, Lublin, Poland.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Lidia
authors.initials: L
authors.lastname: Zubkiewicz-Usnarska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Helbig
authors.forename: Dariusz
authors.initials: D
authors.lastname: Woszczyk
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozińska
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: Jakub
authors.initials: J
authors.lastname: Dębski
authors.forename: Maria
authors.initials: M
authors.lastname: Podolak-Dawidziak
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
mesh_terms: D004358:Drug Therapy; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy; D054556:Venous Thromboembolism / Q000150:complications*
chemical_list: D005337:Fibrin