Stretton Brandon, Harford Philip, Kovoor Joshua, Bacchi Stephen, Gupta Aashray, Sandhu Jaspreet, Moran Hollie, Edwards Suzanne, Jacobsen Jonathon Henry W, Maddern Guy, Boyd Mark
Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, South Australia, Australia.
University of Adelaide, Discipline of Surgery, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
Surg Pract Sci. 2023 Dec 6;15:100230. doi: 10.1016/j.sipas.2023.100230. eCollection 2023 Dec.
Current guidelines suggest preoperative direct oral anticoagulant levels of < 30-50 ng/ml. However, there is limited evidence to guide this expert consensus. Reviewing assay titres and clinical outcomes may be able to inform perioperative care of the anticoagulated patient. This review aimed to determine whether DOAC assay plasma concentrations are associated with bleeding or systemic embolic events to better appreciate a possible therapeutic or hazardous reference range.
Systematic search, performed by an information specialist using a peer-reviewed search. Main search concepts were direct oral anticoagulant therapy for atrial fibrillation or venous thromboembolism. Data synthesised in narrative and tabular format whilst data that could be pooled was subjected to meta-analysis, using a random effects model. Meta regression was conducted for DOAC peak levels and clinical events. PRISMA guidelines were adhered to.
Of 6717 retrieved publications, a total of 17 studies were included in the systematic review and 14 in the meta-analysis/regression. Studies report clinical outcome follow up ranging from 28 to 128 weeks. For every 10 ng/ml increase in DOAC assay trough and peak levels, the mean number of bleeding cases increases by 0.03(95 %CI: -0.32 -0.38, = 0.84) and 0.09(95 %CI: -3.4 -5.3, = 0.55) respectively, the mean number of major bleed cases increases by 0.01(95 %CI: -0.05 -0.07, = 0.62) and 0.011(95 %CI: -0.32 -0.34, = 0.74) respectively and the mean number of systemic embolic event cases decreases by 0.00039(95 %CI: -0.06 -0.0054, = 0.88) and 0.04(95 %CI: -0.56 -0.48, = 0.77) respectively.
There exists no significant, independent relationship, as determined by a univariate meta regression, between DOAC assay concentrations and a patient's risk of bleeding or systemic embolic embolism. This review also highlights the possibility of an absolute, patient specific DOAC assay concentration that may indicate adequate anticoagulation, above which further increases do not confer an increased risk of bleeding. However, further research to characterise this and its utility in the perioperative setting is required.
当前指南建议术前直接口服抗凝剂水平<30 - 50 ng/ml。然而，指导这一专家共识的证据有限。回顾检测效价和临床结果可能有助于为接受抗凝治疗的患者提供围手术期护理。本综述旨在确定直接口服抗凝剂（DOAC）检测的血浆浓度是否与出血或全身性栓塞事件相关，以便更好地了解可能的治疗或危险参考范围。
由一名信息专家进行系统检索，采用同行评审搜索。主要搜索概念是用于心房颤动或静脉血栓栓塞的直接口服抗凝治疗。数据以叙述和表格形式进行综合，对于可合并的数据，使用随机效应模型进行荟萃分析。对DOAC峰值水平和临床事件进行荟萃回归分析。遵循PRISMA指南。
在检索到的6717篇出版物中，共有17项研究纳入系统评价，14项纳入荟萃分析/回归分析。研究报告的临床结局随访时间为28至128周。DOAC检测谷值和峰值水平每增加10 ng/ml，出血病例的平均数量分别增加0.03（95%CI：-0.32至-0.38，P = 0.84）和0.09（95%CI：-3.4至-5.3，P = 0.55），主要出血病例的平均数量分别增加0.01（95%CI：-0.05至-0.07，P = 0.62）和0.011（95%CI：-0.32至-0.34，P = 0.74），全身性栓塞事件病例的平均数量分别减少0.00039（95%CI：-0.06至-0.0054，P = 0.88）和0.04（95%CI：-0.56至-0.48，P = 0.77）。
经单变量荟萃回归分析确定，DOAC检测浓度与患者出血或全身性栓塞风险之间不存在显著的独立关系。本综述还强调了存在一个绝对的、针对个体患者的DOAC检测浓度的可能性，该浓度可能表明抗凝充分，超过此浓度进一步增加并不会使出血风险增加。然而，需要进一步研究来明确这一点及其在围手术期的实用性。
