Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants

Study Questions:

What is the current evidence regarding laboratory measurement of the anticoagulant activity for dabigatran, rivaroxaban, and apixaban?

Methods:

A systematic review was conducted to explore the relationship between drug levels and coagulation assay results for the three commercially available target-specific oral anticoagulants (TSOACs), dabigatran, rivaroxaban, and apixaban. The authors identified 17 studies for dabigatran, 15 for rivaroxaban, and four for apixaban. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) form.

Results:

For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (aPTT) and prothrombin time (PT/INR) are less sensitive and may be normal at trough drug levels. The dilute thrombin time and Ecarin-based assay show excellent linear correlation across on-therapy drug concentrations, and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linearly correlated over a wide range of drug levels, and may be used for drug quantification. An undetectable anti-Xa activity likely excludes clinically relevant concentrations of rivaroxaban and apixaban. The PT/INR is less sensitive (especially for apixaban) and a normal PT/INR level may not exclude clinically relevant drug effects. The aPTT was insufficiently sensitive for drug concentration or effect for both rivaroxaban and apixaban.

Conclusions:

The authors concluded that each of the three TSOAC agents have variable effects on commonly used coagulation assays. The authors note that more information is needed on the relationship between drug levels and clinical outcomes.

Perspective:

This is a timely review of coagulation laboratory techniques and their effectiveness for monitoring TSOAC agents. The authors conducted a reasonably thorough search for all published studies and nicely summarize their findings in a clinically useful table and figure pairing. While TSOAC agents do not require routine laboratory monitoring, certain clinical scenarios will necessitate the ability to evaluate the degree of anticoagulant effect. The ability to assess for any remaining anticoagulant effect may be particularly beneficial before a high-risk surgical procedure (e.g., cardiac and neurosurgery), when verifying compliance with medication administration, or when managing a patient with life-threatening bleeding. As TSOACs become more commonly prescribed, all clinicians have a responsibility to expand their familiarity with various coagulation laboratory studies beyond the PT/INR and aPTT. Each clinician must familiarize himself/herself with the various coagulation tests performed at his/her laboratory and understand how the various TSOAC agents affect those tests.

Clinical Topics: Novel Agents

Keywords: Vitamin K, Prothrombin Time, Morpholines, Benzimidazoles, Neurosurgery, Thiophenes, Partial Thromboplastin Time, Thrombin Time


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