Bonar Roslyn, Favaloro Emmanuel J, Mohammed Soma, Pasalic Leonardo, Sioufi John, Marsden Katherine
1RCPAQAP Haematology, St Leonards, NSW 2Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, NSW 3Pathology Services, Royal Hobart Hospital, Hobart, Tas, Australia.
Pathology. 2015 Jun;47(4):355-64. doi: 10.1097/PAT.0000000000000252.
The new direct oral anticoagulants (DOACS) dabigatran, rivaroxaban, apixaban and edoxaban provide alternatives to warfarin for treatment and prevention of atrial fibrillation and venous thromboembolic disease in various settings. These have been developed as not requiring laboratory monitoring; however, under certain clinical situations, including recent haemorrhage/thrombosis, emergency surgical procedures, testing may be indicated.The aim of this study was to assess findings of haemostasis laboratory tests for one of the DOACs, dabigatran (Pradaxa), tested across a wide range of laboratory assays.Laboratories (n = 72) enrolled in the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Haematology program were sent set(s) of seven dabigatran spiked plasma samples covering the concentration 0-800 ng/mL. Also, 30 ex vivo patient samples under therapy with dabigatran were assessed.Prothrombin time and activated partial thromboplastin time assays showed some sensitivity to dabigatran; however, a normal result could not inform on drug exclusion. The thrombin time (TT) was very sensitive to dabigatran, and a normal TT could generally be used for drug exclusion. More specialised assays such as the Hemoclot, a direct thrombin inhibition assay, and in-house dilute TT methods, showed good reproducibility and concordance with expected drug levels assessed by mass spectrometry and were effective to quantify drug levels. Dabigatran also affected factor assays, lupus anticoagulant and factor inhibitor measurement, leading to potential misinterpretation of test results. Ex vivo sample testing provided similar and extended information.Dabigatran affects many haemostasis tests. Some can be used to predict the presence, absence or quantity of dabigatran in patient plasma. For others, interference may lead to false conclusions regarding patients' haemostatic status.
新型直接口服抗凝剂（DOACs）达比加群、利伐沙班、阿哌沙班和依度沙班为华法林提供了替代方案，用于在各种情况下治疗和预防心房颤动及静脉血栓栓塞性疾病。这些药物的研发目的是无需实验室监测；然而，在某些临床情况下，包括近期出血/血栓形成、急诊外科手术，可能需要进行检测。本研究的目的是评估针对其中一种DOACs——达比加群（Pradaxa），在广泛的实验室检测方法中进行的止血实验室检测结果。参与澳大利亚皇家病理学家学院质量保证项目（RCPAQAP）血液学项目的实验室（n = 72）收到了七组加标达比加群的血浆样本，浓度范围为0 - 800 ng/mL。此外，还对30份接受达比加群治疗的患者离体样本进行了评估。凝血酶原时间和活化部分凝血活酶时间检测对达比加群有一定敏感性；然而，正常结果无法用于排除药物。凝血酶时间（TT）对达比加群非常敏感，正常的TT通常可用于排除药物。更专业的检测方法，如Hemoclot（一种直接凝血酶抑制检测法）和内部稀释TT方法，显示出良好的重复性，且与通过质谱评估的预期药物水平一致，并且能够有效地定量药物水平。达比加群还影响因子检测、狼疮抗凝物和因子抑制剂测量，可能导致检测结果的潜在误判。离体样本检测提供了类似且更全面的信息。达比加群会影响许多止血检测。一些检测可用于预测患者血浆中达比加群的存在、不存在或数量。对于其他检测，干扰可能导致关于患者止血状态的错误结论。
