title: Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications.
abstract: Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.
authors.affiliation: Central Arkansas Veteran's Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ZangariMaurizio@uams.edu
authors.forename: M
authors.initials: M
authors.lastname: Zangari
authors.forename: F
authors.initials: F
authors.lastname: Saghafifar
authors.forename: E
authors.initials: E
authors.lastname: Anaissie
authors.forename: A
authors.initials: A
authors.lastname: Badros
authors.forename: R
authors.initials: R
authors.lastname: Desikan
authors.forename: A
authors.initials: A
authors.lastname: Fassas
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.forename: A
authors.initials: A
authors.lastname: Toor
authors.forename: D
authors.initials: D
authors.lastname: Whitfield
authors.forename: E
authors.initials: E
authors.lastname: Siegel
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
authors.forename: L
authors.initials: L
authors.lastname: Fink
authors.forename: G
authors.initials: G
authors.lastname: Tricot
mesh_terms: D020016:Activated Protein C Resistance / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005165:Factor V / Q000032:analysis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D012306:Risk; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D019851:Thrombophilia / Q000209:etiology*; D020246:Venous Thrombosis / Q000453:epidemiology*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: C095381:factor V Leiden; D013792:Thalidomide; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D005165:Factor V; D002945:Cisplatin