title: Activated protein C resistance as measured by residual factor V after Russell's viper venom and activated protein C treatment analyzed as a continuous variable in multiple myeloma and normal controls.
abstract: Increased risk of venous thromboembolism (VTE) has been described in multiple myeloma patients, particularly when exposed to immunomodulatory drugs. Epidemiological studies have shown that monoclonal gammopathy of undetermined significance (MGUS) patients also have an increased risk of VTE compared with normal individuals. Acquired activated protein C resistance (APC-R) is an independent risk factor for VTE in hematologic malignancies. We reviewed the records of patients with multiple myeloma and MGUS for APC-R by PEFAKIT APC-R test and compared them to normal individuals. We excluded from the analysis patients with a documented factor V Leiden mutation. The PEFAKIT APC-R is a plasma-based functional prothrombin assay based on ratio of patient clotting time with and without APC. Thirty-three MGUS and 93 multiple myeloma patients were compared with 39 normal individuals. Baseline characteristics from the three groups were similar in terms of age, sex, and performance status. The median APC-R for multiple myeloma, MGUS, and controls were 1, 1.06, and 1.1, respectively. Multiple myeloma patients compared to normal individuals had significantly shorter APC-R (P=0.0012). No significant difference was observed between MGUS and normal individuals (P=0.17). After analyzing APC-R values and multiple coagulation parameters, a significant inverse correlation was found between APC-R and fibrinogen (P=0.0000001) and D-dimer (P=0.045) serum levels and a direct correlation with prothrombin time value (P=0.034). The Pefakit APC-R test measured as continuous variable shows a statistically significant decrease in patients with myeloma compared to normal individuals.
authors.affiliation: Myeloma Program, Division of Hematology, University of Utah, Salt Lake City, Utah, USA. maurizio.zangari@hsc.utah.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Louis
authors.initials: L
authors.lastname: Fink
mesh_terms: D020016:Activated Protein C Resistance / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D005165:Factor V / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy; D011486:Protein C / Q000627:therapeutic use; D012189:Retrospective Studies; D017840:Daboia; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control; D014757:Viper Venoms / Q000627:therapeutic use
chemical_list: D011486:Protein C; D014757:Viper Venoms; D005165:Factor V