Brief Communication Influence of anticoagulant therapy with vitamin K antagonists on plasma levels of coagulation factor VIII Serena Maria Passamonti, Paolo Bucciarelli, Rossella Bader, Ida Martinelli ⁎ Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Department of Internal Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Italy abstract article info Article history: Received 15 October 2009 Received in revised form 15 January 2010 Accepted 17 January 2010 Available online 11 February 2010 Keywords: Factor VIII vitamin K antagonists venous thrombosis Vitamin K-antagonists (VKA) decreases vitamin K coagulation factors. To counterbalance this effect, it has been postulated that non-vitamin K proteins increase during VKA treatment. To investigate if VKA affect FVIII, a cohort of 1772 patients referred from Jan 1997 to Oct 2008 to our Thrombosis Center for a thrombophilia screening after at least 3 months from diagnosis of first venous thrombosis was studied. At the time of blood sampling, 1303 patients had discontinued VKA for at least one month, whereas the remaining 469 were still taking VKA. FVIII was significantly higher in patients on VKA than in those who had discontinued VKA (mean±SD: 144 ± 41 IU/dL and 134 ± 40 IU/dL, respectively, p < 0.0001), also after adjustment for sex, age, body mass index, thrombophilia and time elapsed from thrombosis in a multiple linear regression analysis. In order to avoid overestimation of FVIII levels, patients should be preferentially tested after VKA discontinuation. © 2010 Elsevier Ltd. All rights reserved. Introduction Measurements of the anticoagulant proteins C, S and antithrombin, the search of antiphospholipid antibodies (lupus anticoagulant, anti- cardiolipin and anti β-2 glycoprotein I antibodies), DNA analysis for the gain-of-function mutations in factor V (factor V Leiden) and prothrom- bin (prothrombin G20210A) and total plasma homocysteine are part of the thrombophilia workup of patients with previous venous thrombosis. Recently, measurement of coagulation factor VIII (FVIII) has been added to the thrombophilia screening, due to the consistent findings of an association between high levels of FVIII and a 3 to 5-fold increased risk of venous thrombosis [1,2]. In patients with venous thrombosis high FVIII levels persist over time, are not totally attributable to the acute phase reaction and may be genetically determined [3]. FVIII is a non vitamin K- dependent factor that plays a key role in the intrinsic coagulation pathway. FVIII is an acute phase protein that increases in the presence of inflammation [4], cancer [5], liver cirrhosis [6], pregnancy [7] and oral contraceptive use [8]. Males and elderly individuals also have high FVIII levels [8]. Whether or not VKA affects FVIII measurement is a matter of debate. After a first observation of increased FVIII levels during anticoagulant therapy with VKA in the mid ‘60 s [9], only one study of small sample size addressed this issue [10]. Another study did show an up-regulation of the non vitamin K-dependent factors to balance the reduction of the vitamin K-dependent factors during VKA therapy, but FVIII was not measured [11]. To investigate whether or not anticoagu- lant therapy with VKA affects measurement of FVIII, we compared a group of patients with previous venous thrombosis who were still on VKA to those who had discontinued such therapy. In addition, we measured factor VIII in a control group of healthy individuals. Design and methods Patients Between January 1994 and October 2008, 2195 patients were consecutively referred to our Thrombosis Center for a thrombophilia workup after a first episode of venous thrombosis. To avoid the effect of the acute phase on FVIII measurement, 416 patients who had venous thrombosis within three months before blood sampling were excluded. Hence, 1773 patients formed the study cohort. Of them, 1304 had discontinued VKA for at least one month, whereas the remaining 469 were still on VKA at the time of blood sampling (89% used warfarin and 11% acenocumarol). Among the latter, 83 patients returned to the Center after at least one month from VKA withdrawal to complete thrombophilia screening with protein C and protein S measurements (because these anticoagulant proteins are lowered by VKA), and FVIII was re-measured. The control group was formed of 886 healthy individuals referred to the Center in the same period of time as patients and were their friends or partners. Patients and controls gave their informed consent to the study. Laboratory tests FVIII was measured with one-stage coagulation bioassay using factor VIII-deficient plasma as substrate and the activated partial Thrombosis Research 126 (2010) 243–245 ⁎ Corresponding author. Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan, Via Pace, 9, 20122 Milan, Italy. Tel.: + 39 02 55035468; fax: + 39 02 55034439. E-mail address: martin@policlinico.mi.it (I. Martinelli). 0049-3848/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2010.01.017 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres