Rousseau Aurélie, Van Dreden Patrick, Mbemba Elisabeth, Elalamy Ismail, Larsen Annette, Gerotziafas Grigoris T
INSERM U938, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
Research and Development, Diagnostica Stago, Gennevilliers, France.
Thromb Res. 2015 Dec;136(6):1273-9. doi: 10.1016/j.thromres.2015.08.009. Epub 2015 Sep 3.
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).
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.
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.
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.
癌细胞可能会改变抗血栓药物的疗效。为探究这种可能性，本研究比较了低分子肝素依诺肝素以及Xa因子特异性抑制剂（阿哌沙班和磺达肝癸钠）抑制胰腺腺癌细胞（BXPC3）和人乳腺癌细胞（MCF7）引发的凝血酶生成的能力。
将添加了阿哌沙班、磺达肝癸钠或依诺肝素的贫血小板（PPP）或富血小板血浆（PRP）样本加入含有癌细胞的微孔板中，并评估凝血酶生成情况。在对照实验中，用组织因子试剂引发凝血酶生成。
三种抗血栓药物均以浓度依赖的方式抑制凝血酶生成。BXPC3和MCF7细胞以不同强度逆转了所研究药物的作用。根据癌症的组织学类型，阿哌沙班的抗血栓效率得以保留或部分逆转。与阿哌沙班相比，磺达肝癸钠更容易受到癌细胞存在的影响。BXCP3或MCF7细胞对依诺肝素抗血栓效力的影响与对阿哌沙班的影响程度相似。
癌细胞类型是Xa因子特异性抑制剂抗血栓效率的决定因素。相比之下，它对依诺肝素的效力没有显著影响。本研究表明，癌细胞类型对特异性Xa抑制剂抗血栓活性的影响不容忽视。在设计针对不同组织学类型癌症患者的直接口服活性FXa抑制剂剂量探索研究时，必须考虑这一点。
