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Weight-adjusted dalteparin for prevention of vascular thromboembolism in advanced pancreatic cancer patients decreases serum tissue factor and serum-mediated induction of cancer cell invasion

Maraveyas, Anthonya; Ettelaie, Camilleb; Echrish, Husseina; Li, Chaob; Gardiner, Ericc; Greenman, Johna; Madden, Leigh Aa

Blood Coagulation & Fibrinolysis: July 2010 - Volume 21 - Issue 5 - p 452–458
doi: 10.1097/MBC.0b013e328338dc49
ORIGINAL ARTICLE
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The aim of the present study was to assess the role of tissue factor and serum-induced cell invasion in patients with advanced pancreatic cancer (APC). A cohort of 39 patients with APC, without thrombosis, receiving chemotherapy, were entered in a randomized controlled trial (ISRCTN = 76464767) of thromboprevention with weight-adjusted dalteparin (WAD). A total of 19 patients received WAD, the remaining 20 acting as a control group. Serum from baseline and week 8 was analysed for circulating-tissue factor antigen using ELISA. Circulating-tissue factor antigen rose from 324 pg/ml, [interquartile range (IQR) 282–347 pg/ml] to 356 pg/ml, (IQR 319–431 pg/ml) in controls (C), and decreased in the dalteparin-treated group (D) from 336 pg/ml (IQR 281–346 pg/ml) to 303 pg/ml (IQR 274–339 pg/ml). The difference in median percentage change between D and C was statistically significant [−4.0 (D) vs. 4.7 (C); P = 0.005, n = 39]. Serum-induced cellular invasion of MIA-Paca-2 cells in response to patient serum was studied using a Boyden chamber assay in 30 patients (14 WAD and 16 C). The median percentage change between C and D was significant [+54.9 (C) vs. −21.9 (D) P = 0.025, n = 30]. There was a weak correlation between BB-tissue factor reduction and cellular invasion reduction (Spearman) [0.384 (P = 0.037, n = 30)]. APC patients treated with WAD have lower tissue factor antigen levels and attenuated induction of cellular invasion in their blood. These assays may provide useful markers to guide appropriate dalteparin (and other low-molecular weight heparin) dosing schedules to optimize anticancer effects of dalteparin in APC.

aDivision of Cancer, Postgraduate Medical Institute in Association with Hull York Medical School, UK

bBiomedical Section, Department of Biological Sciences, University of Hull, Hull, UK

cFreelance Statistical Consultant

Received 7 December, 2009

Revised 15 January, 2010

Accepted 14 February, 2010

Correspondence to Dr Leigh A. Madden, Postgraduate Medical Institute, University of Hull, Cottingham Road, Hull HU6 7RX, UK Tel/fax: +44 1482 466031; e-mail: l.a.madden@hull.ac.uk

© 2010 Lippincott Williams & Wilkins, Inc.