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Xa 因子抑制对周围动脉疾病患者凝血、血小板反应性和血栓形成的影响。

Impact of Factor Xa Inhibition on Coagulation, Platelet Reactivity, and Thrombosis in Patients with Peripheral Artery Disease.

机构信息

Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.

Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.

出版信息

Ann Vasc Surg. 2023 Nov;97:211-220. doi: 10.1016/j.avsg.2023.08.004. Epub 2023 Aug 30.

Abstract

BACKGROUND

The role of thrombin in vascular pathology is a focus of investigation. The incorporation of direct Factor Xa inhibition into practice patterns is based on its theoretical dual-pathway attenuation of both thrombin generation and platelet aggregation. However, quantification of the effect of direct anti-Xa medications on platelet function is not established. Thromboelastography with platelet mapping (TEG-PM) leverages dual-pathway metrics to provide comprehensive coagulation profiles. We evaluated the effects of direct oral anticoagulants (DOACs) on coagulation and platelet function profiles and correlate these data with postoperative major adverse limb events (MALEs) in patients with PAD.

METHODS

We conducted a prospective study of patients undergoing lower extremity revascularization with serial perioperative TEG-PM analysis. Patients on DOACs were compared to those not on DOACs, and stratified by concurrent mono-antiplatelet or dual-antiplatelet regimens (MAPT/DAPT). Postoperative MALE was recorded and difference in antithrombotic regimens and TEG-PM analysis compared between groups.

RESULTS

Four hundred seventy-one samples from 141 patients were analyzed. Twenty-nine point five percent were reflective of circulating DOAC therapy. Compared to MAPT alone, patients on DOAC + MAPT exhibited longer time to clot formation (R-time) [7.4 (±2.4) vs. 6.7 (±2.7); P < 0.02], but less platelet inhibition. Patients on DAPT exhibited greater platelet inhibition compared to either group [23.7 (±26.9) vs. 31.0 (±28.3) vs. 42.2 (±31.2); P < 0.01]. Patients who experienced MALE were more likely to be on DOAC therapy [43.8% vs. 22.0% P = 0.02]. Thromboelastography with platelet mapping analysis from patients who experienced MALE also demonstrated longer R-time [8.6 (±3.9 vs. 7.3 (±3.0); P = 0.05] and increased maximum clot amplitude (MA) [66.7 (±4.2) vs. 61.8 (±8.2); P = 0.001].

CONCLUSIONS

Direct oral anticoagulant therapy resulted in a prolonged R-time but had no impact on platelet inhibition. Patients who experienced MALE were more often on DOACs and demonstrated an increased R-time, but also showed greater platelet reactivity evident by increased MA, suggesting DOACs may not be effective at protecting against MALE. Further research comparing DOAC therapy to a DAPT approach may add clarity to emerging multimodal antithrombotic recommendations.

摘要

背景

凝血酶在血管病理学中的作用是研究的焦点。将直接因子 Xa 抑制物纳入实践模式是基于其对凝血酶生成和血小板聚集的双重途径衰减的理论。然而,直接抗-Xa 药物对血小板功能的影响尚未确定。血栓弹力图与血小板图谱(TEG-PM)利用双途径指标提供全面的凝血谱。我们评估了直接口服抗凝剂(DOACs)对凝血和血小板功能谱的影响,并将这些数据与 PAD 患者的术后主要不良肢体事件(MALEs)相关联。

方法

我们对接受下肢血运重建的患者进行了前瞻性研究,进行了围手术期 TEG-PM 分析的系列检测。比较了 DOAC 患者与未服用 DOAC 的患者,并根据同时使用单一抗血小板或双重抗血小板方案(MAPT/DAPT)进行分层。记录术后 MALEs,并比较组间抗血栓形成方案和 TEG-PM 分析的差异。

结果

分析了 141 名患者的 471 个样本。29.5%反映了循环 DOAC 治疗。与 MAPT 单独治疗相比,DOAC+MAPT 组患者的凝血酶形成时间(R 时间)更长[7.4(±2.4)比 6.7(±2.7);P<0.02],但血小板抑制作用较弱。与任何一组相比,DAPT 组患者的血小板抑制作用更强[23.7(±26.9)比 31.0(±28.3)比 42.2(±31.2);P<0.01]。发生 MALEs 的患者更有可能接受 DOAC 治疗[43.8%比 22.0%,P=0.02]。发生 MALEs 的患者的血栓弹力图与血小板图谱分析也显示 R 时间更长[8.6(±3.9 比 7.3(±3.0);P=0.05]和最大凝块幅度(MA)增加[66.7(±4.2)比 61.8(±8.2);P=0.001]。

结论

直接口服抗凝剂治疗导致 R 时间延长,但对血小板抑制无影响。发生 MALEs 的患者更常接受 DOAC 治疗,R 时间延长,同时血小板反应性增加,表现为 MA 增加,表明 DOAC 可能无法有效预防 MALEs。比较 DOAC 治疗与 DAPT 方法的进一步研究可能会为新兴的多模式抗血栓形成建议提供更清晰的认识。

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