Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants

Samuelson, Bethany T.; Cuker, Adam; Siegal, Deborah; Crowther, Mark; García, David

doi:10.1016/j.chest.2016.08.1462

Cited by 267 publications

(296 citation statements)

References 117 publications

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“…Calibrated chromogenic anti-Xa assays can be used to analyze the effects of direct Xa inhibitors. 63,64 If such tests are not available, thrombin time or activated partial thromboplastin time (APTT) can be used with limitations for dabigatran and the INR for the assessment of anti-Xa inhibitors. Furthermore, it is important to consider the time since the last dose, potential drug interactions, and also the renal and hepatic function.…”

Section: Monitoring and Safetymentioning

confidence: 99%

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

Lutz

Jurk²,

Schinzel³

2017

IJNRD

103

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Many patients with chronic kidney disease (CKD) receive anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOAC) inhibiting factor Xa or thrombin represent an alternative for VKAs. In patients with acute and chronic kidney disease, caution is warranted, as DOACs can accumulate as they are partly eliminated by the kidneys. Thus, they can potentially increase the bleeding risk in patients with CKD. In patients with an estimated glomerular filtration rate (eGFR) above 60 mL/min, DOACs can be used safely with greater efficacy and safety as compared to VKAs. In patients with CKD 3, DOACs are as effective as VKAs with a lower bleeding rate. The more the renal function declines, the lower is the advantage of DOACs over VKAs. Thus, use of DOACs should be avoided in patients with an eGFR below 30 mL/min, particularly, the compounds with a high renal elimination. Available data suggest that DOACs can also be used safely in older patients. In this review, use of DOACs in comparison with VKAs, heparins, and heparinoids, together with special considerations in patients with impaired renal function will be discussed.

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Section: Monitoring and Safetymentioning

confidence: 99%

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

Lutz

Jurk²,

Schinzel³

2017

IJNRD

103

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“…Nonspecific, ubiquitous esterases rapidly convert this nonpeptide prodrug into a potent, direct, and selective inhibitor of free and fibrin-bound thrombin (Table 1) (20). PK/PD properties are shown in Tables 1 and 2.…”

Section: Direct Thrombin Inhibitor-dabigatran Pharmacologymentioning

confidence: 99%

“…Activated partial thromboplastin time (APTT) is better than prothrombin time (PT) to detect dabigatran presence, but it cannot reliably distinguish between therapeutic and subtherapeutic concentrations (Table 4) (20,23). A normal thrombin time has the best negative predictive value to exclude the presence of dabigatran (20,23).…”

Section: Laboratory Measurement Of Anticoagulant Effectmentioning

confidence: 99%

“…A normal thrombin time has the best negative predictive value to exclude the presence of dabigatran (20,23). Ecarin, a metalloproteinase, cleaves prothrombin to meizothrombin.…”

Section: Laboratory Measurement Of Anticoagulant Effectmentioning

confidence: 99%

“…Its capsule (75 or 150 mg) contains dabigatran-coated pellets with a tartaric acid core to augment bioavailability at low pH. The core increases dyspepsia risk and gastrointestinal bleeding, especially with the 150-mg dose (20). Patients should not chew, break, or open capsules, because bioavailability increases dramatically (21).…”

Section: Direct Thrombin Inhibitor-dabigatran Pharmacologymentioning

confidence: 99%

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Clinical Pharmacology of Oral Anticoagulants in Patients with Kidney Disease

Jain¹,

Reilly²

2018

CJASN

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Oral anticoagulants are commonly used drugs in patients with CKD and patients with ESKD to treat atrial fibrillation to reduce stroke and systemic embolism. Some of these drugs are used to treat or prevent deep venous thrombosis and pulmonary embolism in patients with CKD who undergo knee and hip replacement surgeries. Warfarin is the only anticoagulant that is approved for use by the Food and Drug Administration in individuals with mechanical heart valves. Each oral anticoagulant affects the coagulation profile in the laboratory uniquely. Warfarin and apixaban are the only anticoagulants that are Food and Drug Administration approved for use in patients with CKD and patients with ESKD. However, other oral anticoagulants are commonly used off label in this patient population. Given the acquired risk of bleeding from uremia, these drugs are known to cause increased bleeding events, hospitalization, and overall morbidity. Each anticoagulant has unique pharmacologic properties of which nephrologists need to be aware to optimally manage patients. In addition, nephrologists are increasingly asked to aid in the management of adverse bleeding events related to oral anticoagulant use in patients with CKD and patients with ESKD. This article summarizes the clinical pharmacology of these drugs and identifies knowledge gaps in the literature related to their use.

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Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

et al. 2019

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IMPORTANCE Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. OBJECTIVE To investigate the safety of a standardized perioperative DOAC management strategy. DESIGN, SETTING, AND PARTICIPANTS The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. INTERVENTIONS A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. MAIN OUTCOMES AND MEASURES Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure. RESULTS The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. CONCLUSIONS AND RELEVANCE In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

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Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants

Cited by 267 publications

References 117 publications

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

Clinical Pharmacology of Oral Anticoagulants in Patients with Kidney Disease

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

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