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. 2020 Oct 20;9(19):e017316.
doi: 10.1161/JAHA.120.017316. Epub 2020 Sep 24.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study

Alfonso J Tafur  1   2 , Nathan P Clark  3 , Alex C Spyropoulos  4 , Na Li  5 , Eric Kaplovitch  6 , Kira MacDougall  4 , Sam Schulman  5   7 , Joseph A Caprini  1   2 , James Douketis  5
Affiliations

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study

Alfonso J Tafur et al. J Am Heart Assoc. .

Abstract

Background In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30-day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07-2.99; P=0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08-2.71; P=0.021). Surgical bleed risk classification (high- versus low-risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Keywords: atrial fibrillation; bleeding; direct oral anticoagulant; surgery.

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Conflict of interest statement

Dr Tafur is a consultant for Recovery Force and has received research or educational funding from: Janssen, Bristol‐Myers Squibb, Idorsia, Daichi Sanyo, Stago, and Doasesne. Dr Spyropoulos offers consultancy to Bayer, Ingelheim, Portola, Janssen; and has received research funding from Boehringer Ingelheim and Janssen. Dr. Schulman has grants and personal fees from Boehringer Ingelheim and Octapharma. In addition, he has personal fees from Bayer, Daichi Sankyo, Pfizer, Alnylam, and Sanofi. Dr. Caprini has served in a steering committee for Jansen R&D. In addition, he has served as consultant for Recovery Force, Alexion Pharmaceuticals, and has been in advisory boards for Pfizer and Sanofi. Dr Douketis has served in advisory committees for Pfizer, Sanofi, Leo Pharma, Bristol‐Myers Squibb, Portola, and Janssen. In addition, he has received a patent and royalties from The Merck Manual and Up‐to‐Date. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. The robust influence of surgical bleed risk is compensated by the perioperative bleeding protocol.
We measured a modest influence of patient‐specific risk factors towards the perioperative bleed risk, but the overall likelihood of bleeding and arterial thrombosis was low. CrCl indicates creatinine clearance; and PAUSE, Perioperative Anticoagulant Use for Surgery Evaluation study.
Figure 2
Figure 2. Forest plot of univariate logistic regression for CRNM/MB.
APTT indicates activated partial thromboplastin time; BMI, body mass index; CrCl, creatinine clearance; CRNM/MB, clinically nonmajor bleeding/major bleeding; DOAC, direct oral anticoagulant; INR, international normalized ratio; and OR, odds ratio.
Figure 3
Figure 3. Influence of risk factors by extreme gradient boosting in clinically relevant nonmajor and major bleeding perioperatively.
aPTT indicates activated partial thromboplastin time; BMI, body mass index; CHF, congestive heart failure; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; INR, international normalized ratio; OR, odds ratio; PT, prothrombin time; and TT, thrombin time.
Figure 4
Figure 4. Forest plot of univariate logistic regression for MB.
aPTT indicates activated partial thromboplastin time; BMI, body mass index; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; MB, major bleeding; INR, international normalized ratio; and OR, odds ratio.
Figure 5
Figure 5. Influence of risk factors by extreme gradient boosting in major bleeding perioperatively.
aPTT indicates activated partial thromboplastin time; BMI, body mass index; CHF, congestive heart failure; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; INR, international normarlized ratio; PT, prothrombin time; and TT, thrombtin time.
See this image and copyright information in PMC

References

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