Clinical scenarios in which DOAC drug level measurement may inform clinical management
| Scenario . | Rationale . | Timing of measurement . | Potential impact on clinical decision-making . |
|---|---|---|---|
| GOAL: To assess whether a clinically significant DOAC level is likely to be present in an emergency requiring normal hemostasis | |||
| Prior to an urgent invasive procedure with high bleeding risk | Based on limited data, a DOAC drug level <30 ng/mL is unlikely to warrant anticoagulant reversal for patients requiring an urgent procedure associated with a high risk of bleeding.27 | Random sample for drug level drawn immediately prior to the procedure. | • Use of anticoagulant reversal agent. • Timing of surgery/procedure. • Use of neuraxial anesthesia. |
| Serious bleeding | Based on limited data, a DOAC drug level <50 ng/mL is unlikely to warrant anticoagulant reversal for patients with severe bleeding.27 | Random sample for drug level drawn at presentation with serious bleeding. | • Use of anticoagulant reversal agent. |
| Prior to systemic thrombolysis for acute stroke | Observational data suggest a low risk of intracranial hemorrhage among patients treated with systemic thrombolysis and a DOAC drug level <20-50 ng/mL.30-32 US and European guidelines recommend against use of systemic thrombolysis in patients who ingested a DOAC within the last 48 hours.56,57 | Random sample for drug level drawn at presentation with acute stroke. | • Use of intravenous thrombolysis or alternatives (mechanical thrombectomy). • Surgical approaches. |
| GOAL: To assess for excessively high DOAC levels (above on-therapy range) | |||
| Anticoagulant overdose | The finding of a very high DOAC drug level can confirm a diagnosis of DOAC overdose where the history is unclear. | Random sample for drug level +/- serial drug measurements. | • Reversal agents are not indicated in the absence of bleeding or surgery.58 • Serial drug level measurements can be used to calculate elimination half-life and inform when the patient is no longer at excess risk of bleeding. |
| Severe chronic kidney disease (CKD) | There is uncertainty on the appropriate use and dosing of DOACs in severe renal insufficiency. Phase III trials of DOACs for atrial fibrillation and VTE excluded patients with a creatinine clearance (CrCl) <25-30 mL/min. | Sample for drug level drawn at trough, just before the next dose is due, and after at least 5 doses to ensure drug level is checked at steady state. | • Engage in shared decision- making with the patient or caregiver on alternative options, including switching to a VKA • Plan duration of DOAC interruption for elective surgery/procedure. |
| Pharmacokinetic drug-drug interactions | Apixaban and rivaroxaban are substrates of cytochrome P450 3A4 (CYP3A4), and all DOACs are substrates of p-glycoprotein (p-gp). Strong inhibitors of CYP3A4 and/or p-gp can increase DOAC drug levels and may increase risk of bleeding59 (although high quality data are lacking regarding clinical outcomes). | Sample for drug level drawn at trough (just before the next dose is due) and after at least 5 doses to ensure drug level is checked at steady state.22 | • Change therapy based on drug interaction profile. |
| GOAL: To assess for excessively low DOAC levels (below on-therapy range) | |||
| Malabsorptive gastrointestinal surgery | DOACs are variably absorbed in the stomach and the proximal gastrointestinal (GI) tract. GI cancer or bariatric surgery may reduce DOAC absorption by altering GI motility, reducing stomach acidity, or disrupting the intestinal absorptive surface.40 Patients taking dabigatran or who have undergone highly malabsorptive procedures (such as Roux-en-Y gastric bypass) appear to be at greatest risk of malabsorption.34 | Sample for drug level drawn at peak (1-4 hours after drug ingestion), and/or at trough (just before the next dose is due).22,40 Drug level should be measured after at least 5 doses to ensure steady state is achieved. | • Engage in shared decision- making with the patient or caregiver on switching DOACs based on site of impaired absorption and remeasuring drug level, or switching to a VKA.41 |
| Pharmacokinetic drug-drug interactions | Coadministration of DOACs with strong inducers of p-gp and CYP3A4 (eg, carbamazepine) can decrease DOAC drug levels and may reduce their efficacy60 (although high quality data regarding clinical outcomes are lacking). | Sample for drug level drawn at peak (1-4 hours after drug ingestion) and after at least 5 doses to ensure drug level is checked at steady state. | • Change treatment based on drug interaction profile. |
| Suspected therapeutic failure | Nonadherence to long-term anticoagulation therapy is common (impacting around 15% of patients initiated on a DOAC for atrial fibrillation)61 and associated with a higher risk of thromboembolism. Therefore, checking for adequate drug exposure may be indicated in the workup of a new thromboembolic event sustained while taking a DOAC. | Random sample for drug level drawn at the time of diagnosis of the thromboembolic event. | • Assess and optimize risk factors for nonadherence if applicable (eg, switch from twice daily drug to once daily), or switch anticoagulant (eg, to a VKA with regular INR monitoring). |
| Scenario . | Rationale . | Timing of measurement . | Potential impact on clinical decision-making . |
|---|---|---|---|
| GOAL: To assess whether a clinically significant DOAC level is likely to be present in an emergency requiring normal hemostasis | |||
| Prior to an urgent invasive procedure with high bleeding risk | Based on limited data, a DOAC drug level <30 ng/mL is unlikely to warrant anticoagulant reversal for patients requiring an urgent procedure associated with a high risk of bleeding.27 | Random sample for drug level drawn immediately prior to the procedure. | • Use of anticoagulant reversal agent. • Timing of surgery/procedure. • Use of neuraxial anesthesia. |
| Serious bleeding | Based on limited data, a DOAC drug level <50 ng/mL is unlikely to warrant anticoagulant reversal for patients with severe bleeding.27 | Random sample for drug level drawn at presentation with serious bleeding. | • Use of anticoagulant reversal agent. |
| Prior to systemic thrombolysis for acute stroke | Observational data suggest a low risk of intracranial hemorrhage among patients treated with systemic thrombolysis and a DOAC drug level <20-50 ng/mL.30-32 US and European guidelines recommend against use of systemic thrombolysis in patients who ingested a DOAC within the last 48 hours.56,57 | Random sample for drug level drawn at presentation with acute stroke. | • Use of intravenous thrombolysis or alternatives (mechanical thrombectomy). • Surgical approaches. |
| GOAL: To assess for excessively high DOAC levels (above on-therapy range) | |||
| Anticoagulant overdose | The finding of a very high DOAC drug level can confirm a diagnosis of DOAC overdose where the history is unclear. | Random sample for drug level +/- serial drug measurements. | • Reversal agents are not indicated in the absence of bleeding or surgery.58 • Serial drug level measurements can be used to calculate elimination half-life and inform when the patient is no longer at excess risk of bleeding. |
| Severe chronic kidney disease (CKD) | There is uncertainty on the appropriate use and dosing of DOACs in severe renal insufficiency. Phase III trials of DOACs for atrial fibrillation and VTE excluded patients with a creatinine clearance (CrCl) <25-30 mL/min. | Sample for drug level drawn at trough, just before the next dose is due, and after at least 5 doses to ensure drug level is checked at steady state. | • Engage in shared decision- making with the patient or caregiver on alternative options, including switching to a VKA • Plan duration of DOAC interruption for elective surgery/procedure. |
| Pharmacokinetic drug-drug interactions | Apixaban and rivaroxaban are substrates of cytochrome P450 3A4 (CYP3A4), and all DOACs are substrates of p-glycoprotein (p-gp). Strong inhibitors of CYP3A4 and/or p-gp can increase DOAC drug levels and may increase risk of bleeding59 (although high quality data are lacking regarding clinical outcomes). | Sample for drug level drawn at trough (just before the next dose is due) and after at least 5 doses to ensure drug level is checked at steady state.22 | • Change therapy based on drug interaction profile. |
| GOAL: To assess for excessively low DOAC levels (below on-therapy range) | |||
| Malabsorptive gastrointestinal surgery | DOACs are variably absorbed in the stomach and the proximal gastrointestinal (GI) tract. GI cancer or bariatric surgery may reduce DOAC absorption by altering GI motility, reducing stomach acidity, or disrupting the intestinal absorptive surface.40 Patients taking dabigatran or who have undergone highly malabsorptive procedures (such as Roux-en-Y gastric bypass) appear to be at greatest risk of malabsorption.34 | Sample for drug level drawn at peak (1-4 hours after drug ingestion), and/or at trough (just before the next dose is due).22,40 Drug level should be measured after at least 5 doses to ensure steady state is achieved. | • Engage in shared decision- making with the patient or caregiver on switching DOACs based on site of impaired absorption and remeasuring drug level, or switching to a VKA.41 |
| Pharmacokinetic drug-drug interactions | Coadministration of DOACs with strong inducers of p-gp and CYP3A4 (eg, carbamazepine) can decrease DOAC drug levels and may reduce their efficacy60 (although high quality data regarding clinical outcomes are lacking). | Sample for drug level drawn at peak (1-4 hours after drug ingestion) and after at least 5 doses to ensure drug level is checked at steady state. | • Change treatment based on drug interaction profile. |
| Suspected therapeutic failure | Nonadherence to long-term anticoagulation therapy is common (impacting around 15% of patients initiated on a DOAC for atrial fibrillation)61 and associated with a higher risk of thromboembolism. Therefore, checking for adequate drug exposure may be indicated in the workup of a new thromboembolic event sustained while taking a DOAC. | Random sample for drug level drawn at the time of diagnosis of the thromboembolic event. | • Assess and optimize risk factors for nonadherence if applicable (eg, switch from twice daily drug to once daily), or switch anticoagulant (eg, to a VKA with regular INR monitoring). |