Dias João D, Norem Katherine, Doorneweerd Derek D, Thurer Robert L, Popovsky Mark A, Omert Laurel A
From Clinical Marketing, Haemonetics SA, Signy, Switzerland (Dr Dias); Operations Department (Ms Norem) and Scientific Research & Biomedical (Dr Doorneweerd), Haemonetics Corporation, Rosemont, and Medical Affairs, Haemonetics Corporation, Chicago (Dr Omert), Illinois; Hospital Division (Dr Thurer) and Medical Affairs (Dr Popovsky), Haemonetics Corporation, Braintree, Massachusetts; and Department of Surgery, Einstein Medical Center, Philadelphia, Pennsylvania (Dr Omert). Dr Omert is now with Acquired Bleeding, CSL Behring, King of Prussia, Pennsylvania.
Arch Pathol Lab Med. 2015 May;139(5):665-73. doi: 10.5858/arpa.2014-0170-OA.
The clinical introduction of new oral anticoagulants (NOACs) has stimulated the development of tests to quantify the effects of these drugs and manage complications associated with their use. Until recently, the only treatment choices for the prevention of venous thromboembolism in orthopedic surgical patients, as well as for stroke and systemic embolism in patients with atrial fibrillation, were vitamin K antagonists, antiplatelet drugs, and unfractionated and low-molecular-weight heparins. With the approval of NOACs, treatment options and consequent diagnostic challenges have expanded.
To study the utility of thromboelastography (TEG) in monitoring and differentiating between 2 currently approved classes of NOACs, direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban).
Blood samples from healthy volunteers were spiked with each NOAC in both the presence and absence of ecarin, and the effects on TEG were evaluated.
Both the kaolin test reaction time (R time) and the time to maximum rate of thrombus generation were prolonged versus control samples and demonstrated a dose response for apixaban (R time within the normal range) and dabigatran. The RapidTEG activated clotting time test allowed the creation of a dose-response curve for all 3 NOACs. In the presence of anti-Xa inhibitors, the ecarin test promoted significant shortening of kaolin R times to the hypercoagulable range, while in the presence of the direct thrombin inhibitor only small and dose-proportional R time shortening was observed.
The RapidTEG activated clotting time test and the kaolin test appear to be capable of detecting and monitoring NOACs. The ecarin test may be used to differentiate between Xa inhibitors and direct thrombin inhibitors. Therefore, TEG may be a valuable tool to investigate hemostasis and the effectiveness of reversal strategies for patients receiving NOACs.
新型口服抗凝剂（NOACs）的临床应用推动了量化这些药物效果及处理与其使用相关并发症的检测方法的发展。直到最近，对于骨科手术患者预防静脉血栓栓塞以及房颤患者预防中风和全身性栓塞，唯一的治疗选择是维生素K拮抗剂、抗血小板药物以及普通肝素和低分子肝素。随着NOACs的获批，治疗选择以及随之而来的诊断挑战都有所增加。
研究血栓弹力图（TEG）在监测和区分目前已获批的两类NOACs（直接凝血酶抑制剂（达比加群）和Xa因子抑制剂（利伐沙班和阿哌沙班））方面的效用。
在有和没有蛇毒凝血酶的情况下，将每种NOAC添加到健康志愿者的血液样本中，并评估其对TEG的影响。
与对照样本相比，高岭土试验反应时间（R时间）和血栓形成最大速率时间均延长，并且阿哌沙班（R时间在正常范围内）和达比加群呈现剂量反应。快速TEG活化凝血时间试验可为所有3种NOACs建立剂量反应曲线。在存在抗Xa抑制剂的情况下，蛇毒凝血酶试验可使高岭土R时间显著缩短至高凝范围，但在存在直接凝血酶抑制剂的情况下，仅观察到小幅度且与剂量成比例的R时间缩短。
快速TEG活化凝血时间试验和高岭土试验似乎能够检测和监测NOACs。蛇毒凝血酶试验可用于区分Xa抑制剂和直接凝血酶抑制剂。因此，TEG可能是研究接受NOACs治疗患者的止血情况及逆转策略有效性的有价值工具。
