Schultz Nina H, Tran Hoa T T, Bjørnsen Stine, Henriksson Carola E, Sandset Per M, Holme Pål A
Research Institute of Internal Medicine Oslo University Hospital Oslo Norway.
Department of Haematology Oslo University Hospital Oslo Norway.
Res Pract Thromb Haemost. 2017 Jun 20;1(1):49-56. doi: 10.1002/rth2.12015. eCollection 2017 Jul.
The number of patients under treatment with FXa inhibitors is increasing, but there is no concensus on how to reverse their anticoagulant effect in case of a life-threatening bleeding. A specific antidote is not yet commercially available. Prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are suggested available reversal agents.
To find the most effective reversal agent to apixaban and to determine the optimal dose.
PATIENTS/METHODS: PCC, aPCC, and rFVIIa at concentrations imitating 80%, 100%, and 125% of suggested therapeutic doses were added to blood drawn from apixaban-treated patients (n=30). aPCC was also tested in a 50% dose. Samples from healthy subjects (n=40) were used as controls. Thromboelastometry in whole blood (WB) and thrombin generation in platelet-poor plasma (PPP) were measured to assess the reversal effect.
aPCC shortened clotting time (CT) in WB, and increased the peak thrombin concentration and velocity index in PPP to a greater extent than PCC and rFVIIa. No significant differences were seen between rFVIIa and aPCC on thrombin generation lag time, or between PCC and aPCC on endogenous thrombin potential (ETP). The 50% dose of aPCC had a slightly inferior effect, but was comparable to the other reversal agents.
In this in vitro study the 80% dose of aPCC (40 IU/kg) reversed the anticoagulant effect of apixaban more effectively than the corresponding dose of rFVIIa and PCC both in WB (CT) and PPP (peak, ETP).
接受FXa抑制剂治疗的患者数量正在增加，但对于在发生危及生命的出血时如何逆转其抗凝作用尚无共识。目前尚无商业化的特异性解毒剂。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）被认为是可用的逆转剂。
寻找阿哌沙班最有效的逆转剂并确定最佳剂量。
患者/方法：将浓度模拟建议治疗剂量80%、100%和125%的PCC、aPCC和rFVIIa添加到从接受阿哌沙班治疗的患者（n = 30）抽取的血液中。aPCC也以50%的剂量进行了测试。将来自健康受试者（n = 40）的样本用作对照。测量全血血栓弹力图（WB）和乏血小板血浆（PPP）中的凝血酶生成以评估逆转效果。
aPCC缩短了WB中的凝血时间（CT），并且在PPP中比PCC和rFVIIa更大程度地增加了凝血酶峰值浓度和速度指数。rFVIIa和aPCC在凝血酶生成滞后时间方面无显著差异，PCC和aPCC在内源性凝血酶潜力（ETP）方面也无显著差异。aPCC的50%剂量效果略差，但与其他逆转剂相当。
在这项体外研究中，80%剂量的aPCC（40 IU/kg）在WB（CT）和PPP（峰值、ETP）中比相应剂量的rFVIIa和PCC更有效地逆转了阿哌沙班的抗凝作用。
