title: Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.
abstract: The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland Clinical Research Facility, University College Cork, Ireland Maeve P. Crowley and Barry Kevane are joint first authors.
authors.forename: Maeve P
authors.initials: MP
authors.lastname: Crowley
authors.affiliation: Department of Haematology, Rotunda Hospital, Dublin, Ireland School of Medicine & Medical Science, University College Dublin, Dublin, Ireland SPHERE Research Group, UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin, Ireland Maeve P. Crowley and Barry Kevane are joint first authors.
authors.forename: Barry
authors.initials: B
authors.lastname: Kevane
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Susan I
authors.initials: SI
authors.lastname: O'Shea
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Shane
authors.initials: S
authors.lastname: Quinn
authors.affiliation: School of Medicine & Medical Science, University College Dublin, Dublin, Ireland SPHERE Research Group, UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Karl
authors.initials: K
authors.lastname: Egan
authors.affiliation: Department of Haematology, Cork University Hospital, Cork, Ireland.
authors.forename: Oonagh M
authors.initials: OM
authors.lastname: Gilligan
authors.affiliation: Department of Haematology, Rotunda Hospital, Dublin, Ireland School of Medicine & Medical Science, University College Dublin, Dublin, Ireland SPHERE Research Group, UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin, Ireland Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland fniainle@mater.ie.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Ní Áinle
mesh_terms: D020016:Activated Protein C Resistance / Q000209:etiology*; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D004358:Drug Therapy; D006801:Humans; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D011446:Prospective Studies; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis*; D019851:Thrombophilia; D013927:Thrombosis / Q000209:etiology* / Q000517:prevention & control; D055815:Young Adult
chemical_list: D013917:Thrombin
keywords: MGUS; hypercoagulability; myeloma; thrombosis prophylaxis; venous thromboembolism