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Perioperative Management of Patients Taking Direct Oral Anticoagulants

Author/s: 
James D Douketis, Alex C Spyropoulos

Importance: Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism.

Observations: For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures). For patients undergoing minimal bleeding risk procedures, DOACs may be continued, or if there is concern about excessive bleeding, DOACs may be discontinued on the day of the procedure. Patients undergoing a low to moderate bleeding risk procedure should typically discontinue DOACs 1 day before the operation and restart DOACs 1 day after. Patients undergoing a high bleeding risk procedure should stop DOACs 2 days prior to the operation and restart DOACs 2 days after. With this perioperative DOAC management strategy, rates of thromboembolism (0.2%-0.4%) and major bleeding (1%-2%) are low and delays or cancellations of surgical and nonsurgical procedures are infrequent. Patients taking DOACs who need emergent (<6 hours after presentation) or urgent surgical procedures (6-24 hours after presentation) experience bleeding rates up to 23% and thromboembolism as high as 11%. Laboratory testing to measure preoperative DOAC levels may be useful to determine whether patients should receive a DOAC reversal agent (eg, prothrombin complex concentrates, idarucizumab, or andexanet-α) prior to an emergent or urgent procedure.

Conclusions and relevance: When patients who are taking a DOAC require an elective surgical or nonsurgical procedure, standardized management protocols can be applied that do not require testing DOAC levels or heparin bridging. When patients taking a DOAC require an emergent, urgent, or semiurgent surgical procedure, anticoagulant reversal agents may be appropriate when DOAC levels are elevated or not available.

Keywords 
Perioperative oral anticoagulants

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

Author/s: 
Kearon, C, de Wit, K, Parpia, S, Schulman, S, Afilalo, M, Hirsch, A, Spencer, FA, Sharma, S, D'Aragon, F, Deshaies, JF, Le Gal, G, Lazo-Langer, A, Wu, C, Rudd-Scott, L, Bates, SM, Julian, JA, PEGeD Study Investigators

BACKGROUND:

Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP.

METHODS:

We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism.

RESULTS:

A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9).

CONCLUSIONS:

A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).

Keywords 
pulmonary embolism PE d-dimer CT computed tomography

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review

Author/s: 
Baumgartner, C., de Kouchkovsky, I., Whitaker, E., Fang, M.C.

Abstract

BACKGROUND:

Vitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear benefits and risks of periprocedural bridging in patients with previous venousthromboembolism, we aimed to assess recurrent venous thromboembolism and bleeding outcomes with and without bridging in this population.

METHODS:

We performed a systematic review searching the PubMed and Embase databases from inception to December 7, 2017 for randomized and nonrandomized studies that included adults with previous venous thromboembolism requiring VKA interruption to undergo an elective procedure, and that reported venous thromboembolism or bleeding outcomes. Quality of evidence was graded by consensus.

RESULTS:

We included 28 cohort studies (20 being single-arm cohorts) with, overall, 6915 procedures for analysis. In 27 studies reporting perioperative venous thromboembolism outcomes, the pooled incidence of recurrent venous thromboembolism with bridging was 0.7% (95% confidence interval [CI], 0.4%-1.2%) and 0.5% (95% CI, 0.3%-0.8%) without bridging. Eighteen studies reported major or nonmajor bleeding outcomes. The pooled incidence of any bleeding was 3.9% (95% CI, 2.0%-7.4%) with bridging and 0.4% (95% CI, 0.1%-1.7%) without bridging. In bridged patients at high thromboembolic risk, the pooled incidence for venous thromboembolism was 0.8% (95% CI, 0.3%-2.5%) and 7.5% (95% CI, 3.1%-17.4%) for any bleeding. Quality of available evidence was very low, primarily due to a high risk of bias of included studies.

CONCLUSIONS:

Periprocedural bridging increases the risk of bleeding compared with VKA interruption without bridging, without a significant difference in periprocedural venous thromboembolism rates.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

Anticoagulants; Bleeding; Bridging; PROSPERO; Periprocedural; Venous thromboembolism; registration number CRD42017074710

Keywords 
warfarin risk assessment hemorrhage anticoagulants bleeding Bridging Periprocedural
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