Schultz Nina Haagenrud, Tran Hoa Thi Tuyet, Bjørnsen Stine, Henriksson Carola Elisabeth, Sandset Per Morten, Holme Pål Andre
Research Institute of Internal Medicine, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.
Department of Haematology, Oslo University Hospital, Box 4950, Nydalen, N-0424 Oslo, Norway.
Thromb J. 2017 Feb 20;15:6. doi: 10.1186/s12959-017-0129-1. eCollection 2017.
An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons.
Blood samples from rivaroxaban-treated patients ( 50) were spiked with PCC, aPCC and rFVIIa at concentrations imitating 80%, 100% and 125% of suggested therapeutic doses. The reversal effect was assessed by thromboelastometry in whole blood and a thrombin generation assay (TGA) in platelet-poor plasma. Samples from healthy subjects ( 40) were included as controls.
In thromboelastometry measurements, aPCC and rFVIIa had a superior effect to PCC in reversing the rivaroxaban-induced lenghtening of clotting time (CT). aPCC was the only haemostatic agent that shortened the CT down to below the control level. Compared to healthy controls, patients on rivaroxaban also had a prolonged lag time and decreased peak concentration, velocity index and endogenous thrombin potential (ETP) in platelet-poor plasma. aPCC reversed these parameters more effectively than rFVIIa and PCC. There were no differences in efficacy between 80%, 100% and 125% doses of aPCC.
aPCC seems to reverse the anticoagulant effect of rivaroxaban more effectively than rFVIIa and PCC by evaluation with thromboelastometry and TGA in vitro.
越来越多的患者接受直接口服抗凝剂（DOACs）治疗，但逆转抗凝作用的最佳方法尚不清楚。目前尚无特异性解毒剂，在发生大出血时，凝血酶原复合物浓缩物（PCC）、活化凝血酶原复合物浓缩物（aPCC）和重组凝血因子VIIa（rFVIIa）被不同程度地用作逆转剂。我们旨在确定在因治疗目的服用利伐沙班的患者的血液样本中，逆转利伐沙班作用的最有效止血剂及其剂量。
将PCC、aPCC和rFVIIa以模拟建议治疗剂量的80%、100%和125%的浓度加入到服用利伐沙班患者的血样（n = 50）中。通过全血血栓弹力图和乏血小板血浆中的凝血酶生成试验（TGA）评估逆转效果。纳入健康受试者的样本（n = 40）作为对照。
在血栓弹力图测量中，aPCC和rFVIIa在逆转利伐沙班引起的凝血时间（CT）延长方面比PCC具有更优效果。aPCC是唯一能将CT缩短至对照水平以下的止血剂。与健康对照相比，服用利伐沙班的患者在乏血小板血浆中的延迟时间也延长，峰值浓度、速度指数和内源性凝血酶潜力（ETP）降低。aPCC比rFVIIa和PCC更有效地逆转了这些参数。80%、100%和125%剂量的aPCC在疗效上无差异。
通过体外血栓弹力图和TGA评估，aPCC似乎比rFVIIa和PCC更有效地逆转利伐沙班的抗凝作用。
