Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Evidence Prime Inc, Cracow, Poland.
Blood Adv. 2019 Mar 12;3(5):789-796. doi: 10.1182/bloodadvances.2018025163.
Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.
接受国际标准化比值(INR)在 4.5 至 10 之间的维生素 K 拮抗剂(VKA)治疗的患者出血风险增加。我们系统地回顾了文献,以评估在 INR 在 4.5 至 10.0 之间且无出血的 VKA 治疗患者中给予维生素 K 的有效性和安全性。我们于 2018 年 4 月在 Medline、Embase 和 Cochrane 数据库中搜索了相关的随机对照试验。搜索策略包括维生素 K 给药和 VKA 相关术语。我们还查阅了相关研究的参考文献,并联系了该领域的专家以获取相关论文。两名调查员独立筛选和收集数据。使用推荐评估、制定与评价(Grading of Recommendations Assessment,Development and Evaluation,GRADE)评估证据确定性,并计算风险比(RR)。纳入了 6 项研究(1074 名参与者)进行综述和荟萃分析。汇总估计表明,维生素 K 给药与死亡率(RR = 1.42;95%置信区间 [CI],0.62-2.47)、出血(RR = 2.24;95%CI,0.81-7.27)和血栓栓塞(RR = 1.29;95%CI,0.35-4.78)风险增加无关,但由于严重不精确,证据确定性为中等,CI 包括获益和危害的可能性。接受维生素 K 治疗的患者达到目标 INR 的可能性略有增加(1.95;95%CI,0.88-4.33),但由于严重的偏倚风险、不一致性和不精确性,证据确定性非常低。我们的研究结果表明,除了暂时停止 VKA 治疗外,INR 在 4.5 至 10.0 之间且无出血的 VKA 治疗患者不太可能从维生素 K 给药中获益。