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SummaryHeparansulfate-proteoglycans (HSPGs) interact via their polyanionic heparansulfate (HS) side chains with a variety of proteins on the cell surface or within the extracellular matrix membrane. The large number of heparin/HS binding proteins form a highly interconnected functional network, which has been termed as the heparin/HS interactome and is functionally linked to physiological and pathological processes. The aim of this study was to investigate the global effect of these protein-HSPG interactions on the tumourigenicity of two breast cancer cell lines (MCF-7 and MDA-MB-231). Cancer cells were cultured in serum-free medium and treated with a concentration of heparin which was capable of modulating HS/ligand interaction. Microarray analysis of MCF-7 cells cultured under these conditions showed that expression of 105 of 1,357 genes potentially related to the pathogenesis of breast neoplasm was significantly altered by heparin treatment. The changes in gene expression correlated with a less tumourigenic phenotype, including reduction of cell adhesive, invasive and migratory properties. These effects were associated with an inhibition of the PI3K/Akt and Raf/MEK/ERK signalling pathways. The modulatory effect of heparin on HS-associated activity was confirmed with one example of heparin/HS interactomes, transforming growth factor β (TGFβ). The innate TGFβ activity of MCF-7 cells was reduced by heparin treatment, with specific interruption of the TGFβ–Smad signalling pathway. The pro-tumourigenic contribution of the heparin/HS interactomes was verified in cells in which HSPG synthesis was blocked using β-xyloside. In conclusion, the interaction between cell surface HPSGs and innate heparin/HS interactomes makes a significant contribution to the tumourigenicity.

A pilot study was performed to compare the thromboprophylactic effect of danaparoid, enoxaparin and dalteparin in patients with hip fracture. The study was a prospective, randomised assessor-blind, four-centre trial. Prophylaxis was given for 9–11 days, whereafter bilateral phlebography was performed. A total of 197 patients were randomised. There were no statistically significant differences in the frequency of deep vein thrombosis, in blood loss or bleeding complications between the three prophylaxis groups. In conclusion, this moderately sized study revealed no statistically significant difference in efficacy or safety between danaparoid, enoxaparin and dalteparin in patients undergoing hip fracture surgery.

SummaryThe effect of incubation of plasma with lipoprotein lipase on factor VII coagulant (FVII: C) activity was examined in 40 patients, 22 male and 18 female, aged 28 to 77 years, with history of venograph-ically proven deep venous thrombosis (DVT). While the mean (± SEM) FVII: C activity of the 40 patients was 100.9 ± 4.1%, 19 patients had FVII: C activity less than 100%, 11 had 100 to 120% activity and 10 patients had greater than 120% FVII:C activity. The mean triglyceride level of all the patients was 84.0 ± 6.5 mg/dl. The FVII: C activity correlated significantly with triglyceride (r = 0.36; n = 40; p = 0.021). There was about 30% average loss of FVII: C activity upon incubation of plasma with lipoprotein lipase. The mean activity loss increased from 23.8% to 31.5% and 42.6% in patients whose FVII:C activity levels were less than 100%, between 100 and 120% and more than 120% respectively, the variation in the means being statistically significant (p

Background Congestive heart failure (CHF) is associated with a hypercoagulable state. Patients and Methods A single-center, randomized, double-blind, placebo-controlled trial was performed to test the hypothesis that a prophylactic dose of low molecular weight heparin (bemiparin sodium 3500 IU/daily subcutaneously) will modify a hypercoagulable state in CHF. This study included 100 patients with CHF (New York Heart Association classification II to IV). All patients underwent 3 blood tests, at baseline (before randomization), 24 hours after randomization, and before hospital discharge or within 10 days from randomization. Results In comparison of baseline bemiparin sodium 3500 IU/daily subcutaneously with after 24 hours, there was a significant decrease in plasma levels of D-dimer (−13.8 ng/mL; P = .01) and prothrombin fragments 1 and 2 (−0.11 nmol/L; P = .01), whereas protein C was significantly increased (+3.5%; P = .03). In comparison of baseline bemiparin sodium 3500 IU/daily subcutaneously with after 4 to 10 days of therapy, there were significantly decreased plasma levels for factor VII:c (−3.0%; P = .01), D-dimer (−44.0 ng/mL; P = .002), and thrombin-antithrombin complex (−0.7 μg/L; P = .0001), whereas protein C was significantly increased (+16.0%; P = .03). On the other hand, in the group of patients treated with placebo after 24 hours, a significant decrease was observed of protein C (−4.0%; P = .04). After 24 hours, the changes from baseline were significantly different for some of the hemostatic factors in comparison of bemiparin sodium 3500 IU/daily and placebo (factor VII:c: −1.7 versus 0.0%; P = .04; D-dimer: −14 versus +24.3 ng/mL; P = .009; prothrombin fragments 1 and 2: −0.11 versus +0.11 nmol/L; P = .01; protein C: +3.5 versus −4.0%; P = .01). Also at discharge, the changes from baseline were different for some of the markers in comparison of bemiparin sodium with placebo (D-dimer: −44 versus 3.8 ng/mL; P = .002; thrombin-antithrombin complex: −0.70 versus +0.14 μg/L; P = .002; protein C: +16.0 versus +0.5%; P = .02). Conclusion Our findings suggest that a hypercoagulable state in heart failure can be modified with bemiparin sodium therapy. (Am Heart J 2002;143:e3.)