Martin Anne-Céline, Kyheng Maeva, Foissaud Vincent, Duhamel Alain, Marijon Eloi, Susen Sophie, Godier Anne
Université de Paris, Innovations Thérapeutiques en Hémostase, INSERM 1140, 4 avenue de l'observatoire, F-75006 Paris, France.
Hôpital Européen Georges Pompidou, Service de Cardiologie, 20 Rue Leblanc, F-75015 Paris, France.
J Clin Med. 2020 Jan 27;9(2):350. doi: 10.3390/jcm9020350.
Atrial fibrillation (AF) catheter ablation is performed in patients receiving direct oral anticoagulants (DOACs) with intra-procedural unfractionated heparin (UFH) administration to achieve activated clotting time (ACT) at 300 s, as for vitamin K antagonist (VKA). We determined whether ACT monitoring might be transposed from VKA to DOAC-treated patients. Blood was taken from 124 patients receiving uninterrupted dabigatran, rivaroxaban, apixaban, or VKA or being untreated. DOAC concentration or INR (VKA) were measured. ACT was determined at baseline, and after spiking with UFH doses equivalent to 1000, 2500, 5000 and 10000 IU . At baseline, anticoagulants prolonged ACT differently, ACT was longer with dabigatran and shorter with apixaban despite similar concentrations. ACT strongly correlated with INR and dabigatran concentration, but not with apixaban or rivaroxaban concentrations. Moreover, UFH effects on ACT prolongation depended on the anticoagulant: dose-response curves in samples with VKA and dabigatran were parallel whereas ACT prolongation in response to UFH was significantly smaller with rivaroxaban and especially apixaban. Therefore, UFH to achieve ACT at 300 s might be transposed from VKA to uninterrupted dabigatran-treated patients but not to patients receiving FXa-inhibitors, especially apixaban. Targeting 300 s might expose to UFH overdosing and bleeding, questioning the current anticoagulation strategy.
在接受直接口服抗凝剂（DOACs）治疗的患者中进行心房颤动（AF）导管消融时，术中给予普通肝素（UFH）以达到与维生素K拮抗剂（VKA）相同的300秒活化凝血时间（ACT）。我们确定了ACT监测是否可以从VKA治疗的患者转移到DOAC治疗的患者。从124例接受达比加群、利伐沙班、阿哌沙班不间断治疗或VKA治疗或未接受治疗的患者中采集血液。测量DOAC浓度或INR（VKA）。在基线时以及用相当于1000、2500、5000和10000 IU的UFH剂量加样后测定ACT。在基线时，抗凝剂对ACT的延长作用不同，尽管浓度相似，但达比加群使ACT延长，阿哌沙班使ACT缩短。ACT与INR和达比加群浓度密切相关，但与阿哌沙班或利伐沙班浓度无关。此外，UFH对ACT延长的作用取决于抗凝剂：VKA和达比加群样本中的剂量反应曲线平行，而利伐沙班尤其是阿哌沙班对UFH反应的ACT延长明显较小。因此，将ACT达到300秒的UFH应用可以从VKA治疗的患者转移到达比加群不间断治疗的患者，但不能转移到接受FXa抑制剂治疗的患者，尤其是阿哌沙班治疗的患者。将目标设定为300秒可能会导致UFH过量和出血，这对当前的抗凝策略提出了质疑。
