Cancer cells BXPC3 and MCF7 differentially reverse the inhibition of thrombin generation by apixaban, fondaparinux and enoxaparin.
BACKGROUND
Cancer cells may alter the efficiency of the antithrombotic agents. To explore this possibility, the present study compared the capacity of the LMWH enoxaparin and the specific inhibitors of Xa (apixaban and fondaparinux) to inhibit thrombin generation triggered by pancreas adenocarcinoma cells (BXPC3) and human breast carcinoma cells (MCF7).


METHODS
Samples of platelet poor (PPP) or platelet rich plasma (PRP) spiked with apixaban, fondaparinux or enoxaparin were added in micro wells carrying cancer cells and assessed for thrombin generation. In the control experiment thrombin generation was triggered with tissue factor reagent.


RESULTS
The three antithrombotics inhibited thrombin generation in a concentration dependent manner. The BXPC3 and MCF7 cells reversed in a different intensity the effect of the studied agents. According to the histological type of the cancer the antithrombotic efficiency of apixaban was preserved or partially reversed. Fondaparinux, was more vulnerable to the presence of cancer cells as compared to apixaban. The effect of BXCP3 or MCF7 cells on the antithrombotic potency of enoxaparin was of similar magnitude as that on apixaban.


CONCLUSIONS
The type of cancer cells is determinant for the antithrombotic efficiency of the specific factor Xa inhibitors. In contrast it does not significantly influence the potency of enoxaparin. The present study shows that the impact of the type of cancer cells on the antithrombotic activity of the specific Xa inhibitors should not be neglected. This has to be taken into consideration for the design of dose-finding studies of the direct orally active FXa inhibitors in patients with different histological types of cancer.
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
Aurélie
A
Rousseau
Research and Development, Diagnostica Stago, Gennevilliers, France.
Patrick
P
Van Dreden
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
Elisabeth
E
Mbemba
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France; Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France.
Ismail
I
Elalamy
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
Annette
A
Larsen
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France; Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France. Electronic address: grigorios.gerotziafas@aphp.fr.
Grigoris T
GT
Gerotziafas
D000925:Anticoagulants / Q000737:chemistry*; D001792:Blood Platelets / Q000166:cytology; D001943:Breast Neoplasms / Q000150:complications / Q000276:immunology*; D045744:Cell Line, Tumor; D017984:Enoxaparin / Q000737:chemistry*; D015951:Factor Xa / Q000737:chemistry; D005260:Female; D005343:Fibrinolytic Agents / Q000737:chemistry*; D000077425:Fondaparinux; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D010190:Pancreatic Neoplasms / Q000150:complications / Q000276:immunology*; D011134:Polysaccharides / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry*; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D013917:Thrombin; D015951:Factor Xa; D000077425:Fondaparinux
Anticoagulant; Apixaban; Cancer; Fondaparinux; Low molecular weight heparin; NOAC; Thrombin generation