Low molecular weight heparins (LMWHs) and fondaparinux are widely used for prophylaxis and treatment of
venous thromboembolic disease in cancer patients. However, the optimization of the antithrombotic treatment especially
in patients with adenocarcinoma of the pancreas is a challenging issue. The understanding of the mechanism of action of
the LMWHs and fondaparinux in cancer-induced hypercoagulability might help to optimize antithrombotic treatment. To
this aim, we investigated the influence of BXPC3 pancreas adenocarcinoma cells on the antithrombotic activity of
LMWHs and fondaparinux.
Thrombin generation (TG) in normal platelet poor (PPP) and platelet rich plasma (PRP) spiked with clinically relevant
concentrations of dalteparin, enoxaparin, nadroparin tinzaparin and fondaparinux was assessed with the Calibrated Automated
Thrombogram assay. BXPC3 (5 cells/μl) were added to plasma. The mean rate index (MRI) of the propagation
phase of TG and the endogenous thrombin potential (ETP) were analyzed. The IC50 of the studied compounds were determined
and compared on the basis of anti-Xa and anti-IIa equivalent units.
We demonstrate that the specific antithrombin (AT)-dependent anti-Xa activity of LMWHs and fondaparinux almost selectively
inhibits the propagation phase of TG. The synergy between the anti-Xa and anti-IIa activities of LMWHs rather
than the selective inhibition of FXa warrants abrogation of TG. The mean molecular weight and anti-Xa/anti-IIa ratio of
the AT-dependent agents cannot predict the alteration of their capacity to inhibit TG. Tinzaparin was the most potent inhibitor
of TG than the other LMWHs. Enoxaparin was more potent than nadroparin and dalteparin.