Haemophilia and Thrombophilia Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Br J Haematol. 2019 Nov;187(3):377-385. doi: 10.1111/bjh.16091. Epub 2019 Jul 10.
This study describes the use of a simple charcoal product (DOAC-Remove ) to allow haemostasis assays on patients taking direct oral anticoagulants (DOAC). In the proposed algorithm, patients taking DOAC are screened using the dilute thrombin time (dTT) and anti-Xa assay. If either are positive then DOAC-Remove is utilised. In a validation, DOAC-Remove did not interfere with coagulation testing in normal plasma or in patients on DOAC with a known lupus anticoagulant (LA). Of 1566 routine patient samples tested, 125 (8%) had evidence of anti-Xa activity (>0·1 iu/ml) or prolonged dTT suggestive of either a direct/indirect Xa inhibitor or direct thrombin inhibitor. All of these 125 patients had a prolonged dilute Russell viper venom time (dRVVT) screening test and 106 had a LA detected by dRVVT after phospholipid correction. After DOAC-Remove, 91 patients (73%) had a negative dRVVT screen. After further investigation only 9 (7%) had a positive LA. DOAC-Remove prevented 5% of patients having a LA inappropriately detected. DOAC did not significantly affect the LA activated partial thromboplastin time (aPTT) ratio, protein S antigen or protein C activity. DOAC cause low intrinsic factor assays, high prothrombin time/aPTT and high activated protein C sensitivity ratio, which DOAC-Remove reversed (P < 0·05). Despite recommendations, haemostasis testing for patients on DOAC continues; this algorithm aids diagnostic accuracy. Further validation and research are warranted.
本研究描述了一种简单的活性炭产品(DOAC-Remove)在服用直接口服抗凝剂(DOAC)的患者中进行止血检测的应用。在提出的算法中,使用稀释凝血酶时间(dTT)和抗-Xa 测定对服用 DOAC 的患者进行筛选。如果这两个指标中有一个阳性,则使用 DOAC-Remove。在验证中,DOAC-Remove 不会干扰正常血浆中的凝血检测,也不会干扰已知狼疮抗凝剂(LA)的 DOAC 患者中的凝血检测。在检测的 1566 例常规患者样本中,有 125 例(8%)有抗-Xa 活性(>0·1 iu/ml)或 dTT 延长的证据,提示直接/间接 Xa 抑制剂或直接凝血酶抑制剂。所有这些 125 例患者均有延长的稀释 Russell 蝰蛇 venom 时间(dRVVT)筛选试验,106 例经磷脂校正后有 dRVVT 检测到 LA。使用 DOAC-Remove 后,91 例(73%)患者的 dRVVT 筛查结果为阴性。进一步调查后,只有 9 例(7%)患者的 LA 呈阳性。DOAC-Remove 可防止 5%的患者 LA 检测不当。DOAC 不会显著影响 LA 激活的部分凝血活酶时间(aPTT)比值、蛋白 S 抗原或蛋白 C 活性。DOAC 导致低内在因子测定、高凝血酶原时间/aPTT 和高激活蛋白 C 敏感性比值,而 DOAC-Remove 可逆转这些比值(P<0·05)。尽管有相关建议,但仍继续对服用 DOAC 的患者进行止血检测;该算法有助于提高诊断准确性。需要进一步验证和研究。