PRE VERSUS POST-OPERATIVE INITIATION OF WARFARIN THERAPY IN PATIENTS UNDERGOING TOTAL HIP AND KNEE ARTHROPLASTY

C. Cipriano, Nicholas J Erdle, Kai Li, B. Curtin
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Abstract

Background The optimal strategy for postoperative deep venous thrombosis (DVT) prophylaxis remains among the most controversial topics in hip and knee arthroplasty. Warfarin, the most commonly used chemical anticoagulant, initially causes transient hypercoagulability; however the optimal timing of treatment with respect to surgery remains unclear. Our purpose was to evaluate the effects of pre- versus postoperative initiation of warfarin therapy with a primary endpoint of perioperative change in hemoglobin (pre- minus post-operative level), with secondary endpoints of postoperative International Normalized Ratio (INR), drain output, and bleeding/thrombotic events. Methods A quasi-experimental study design was employed, under which patients were assigned to begin taking warfarin the night prior to surgery or the night following surgery based on day of the week seen in clinic. An a priori power analysis was conducted in order to ensure appropriate enrollment to detect a 0.5 g/dL difference in perioperative change in hemoglobin between groups, given an alpha level of 0.05 and beta of 0.80. Based on the results, the study included all primary, elective total hip and knee arthroplasties performed by a single surgeon over a 12 month period. Fifteen patients were excluded (7 chronic anticoagulation, 3 hip fractures, 2 medical contraindications, 3 simultaneous procedures), leaving 165 cases (108 hips, 57 knees) available for study. Of these, 73 received warfarin preoperatively (49 hips, 24 knees) and 92 postoperatively (59 hips, 33 knees). Warfarin was dosed according to a standard nomogram in both groups. INR (on postoperative days 1 and 2), perioperative decrease in hemoglobin (difference between level preoperatively and on postoperative days 1 and 2), and drain outputs were compared between groups using a student t test. Adverse events (transfusions, hematomas, epidural complications, and pulmonary embolus) were compared using two-tailed Fischer9s exact test. Results No statistically significant difference in perioperative hemoglobin change was observed between treatment groups on either postoperative day 1 (mean 3.279 versus 3.377, p=0.6824) or 2 (mean 4.0 versus 4.12, p=0.6831). As expected, the preoperative warfarin group demonstrated higher INRs on both postoperative days 1 (mean 1.18 versus 1.12, p=0.0023) and 2 (mean 1.46 versus 1.31, p=0.0006). Of note, preoperative warfarin dosing was also associated with significantly lower drain outputs (mean 185.4 versus 268.7, p=0.0025). 9 transfusions (4 preoperative dosing, 5 postoperative dosing), 3 hematomas (1 preoperative dosing, 2 postoperative dosing), and 1 pulmonary embolus (preoperative dosing) occurred, but no significant difference could be detected given the numbers available for study. Conclusions Initiation of warfarin pre- rather than postoperatively was not associated with a significant difference in perioperative hemoglobin change, although a significant reduction in drain output was observed. Larger studies are needed to determine whether the risk of adverse events is increased with either dosing strategy.
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全髋关节和膝关节置换术患者术前与术后华法林治疗的比较
背景:髋关节和膝关节置换术后深静脉血栓形成(DVT)预防的最佳策略仍然是最有争议的话题。华法林是最常用的化学抗凝剂,最初会引起短暂性高凝;然而,手术治疗的最佳时机仍不清楚。我们的目的是评估术前与术后开始华法林治疗的效果,主要终点是围手术期血红蛋白变化(术前减去术后水平),次要终点是术后国际标准化比率(INR)、排液量和出血/血栓事件。方法采用准实验研究设计,根据患者的临床表现,将患者分为术前晚或术后晚开始服用华法林。在α水平为0.05和β水平为0.80的情况下,为了确保合适的入组,我们进行了先验功率分析,以检测两组之间围手术期血红蛋白变化的0.5 g/dL差异。基于结果,该研究纳入了所有由单一外科医生在12个月内进行的原发性、选择性全髋关节和膝关节置换术。15例患者被排除(7例慢性抗凝,3例髋部骨折,2例医学禁忌症,3例同时手术),留下165例(108例髋关节,57例膝关节)可供研究。其中,73例术前(49髋,24膝)和92例术后(59髋,33膝)接受华法林治疗。两组均按标准图给药。采用学生t检验比较两组间INR(术后第1和2天)、围手术期血红蛋白下降(术前与术后第1和2天水平的差异)和引流量。不良事件(输血、血肿、硬膜外并发症和肺栓塞)采用双尾fisher精确检验进行比较。结果两组患者术后第1天(平均3.279比3.377,p=0.6824)和第2天(平均4.0比4.12,p=0.6831)围手术期血红蛋白变化差异均无统计学意义。正如预期的那样,术前华法林组在术后第1天(平均1.18比1.12,p=0.0023)和第2天(平均1.46比1.31,p=0.0006)均显示较高的INRs。值得注意的是,术前华法林剂量也与明显较低的引流量相关(平均185.4对268.7,p=0.0025)。发生9例输血(术前给药4例,术后给药5例),3例血肿(术前给药1例,术后给药2例),1例肺栓塞(术前给药),但考虑到可供研究的数量,未发现显著差异。结论:术前使用华法林与术后使用华法林与围手术期血红蛋白变化无显著差异,但观察到引流液排出量显著减少。需要更大规模的研究来确定两种给药策略是否会增加不良事件的风险。
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