Direct Oral Anticoagulants: Correlation of Laboratory Monitoring With Safe Interventional Pain Procedures

The Daring Discourse article by Douketis et al 1 in this issue of Regional Anesthesia and Pain Medicine illustrates the competing priorities that the Guideline Committee faced when formulating the American Society of Regional Anesthesia and PainMedicine (ASRA) guidelines for pain interventional procedures in patients taking anticoagulants. Douketis et al recommended that the ASRA recommendations should have been considered “clinical guidance” in viewof the lack of well-designed studies to support the core recommendations. The Guideline Committee, acting on survey results and stated knowledge deficits of practicing clinicians, felt that it was imperative to provide a framework by which clinicians could make difficult management decisions. The Guideline Committee was explicit in its statement that the grading of recommendations was not possible because of the lack of evidence. Although “guidance” may have been more appropriate wordsmithing, the guideline is one of several that ASRA has published. Thus, operationally, whether one calls something guidance or guideline is largely semantics. Indeed, both ASRA and its European counterparts had previously published guidelines on the direct-acting oral anticoagulants (DOACs), earlier than our pain guidelines, in the absence of adequate supporting evidence. All guidelines should ideally correlate half-life intervals or blood levels of the DOACs, or clotting factor levels, with monitored safety of interventional pain procedures. However, for ASRA and the other societies to postpone the formulation of guidelines until complete information was available would have required several years of time and large population health studies before guidelines could be issued. Thus, the decision to act with partial information versus waiting for complete information was the core dilemma. The Guidelines Committee and our subspecialty constituency felt that pain medicine clinicians were applying the ASRA guidelines on regional anesthesia or other guidelines in their patients receiving pain procedures with occasionally catastrophic consequences because of the largely different procedural complexity and patient/disease demographics. The ASRA recommendations were made after a careful review of the pharmacokinetics of each drug and applying a safe and more conservative interval of 5 half-lives between discontinuation of the drug and interventional pain procedures. Although other societies and experts recommended a 2-half-life interval, wherein 25% of the drug remains in the patient's plasma, the Guideline Committee recommended a 5-half-life interval, where only 3% of the drug remains. This is in agreement with the statement of Douketis et al that “a procedure associated with a high bleed risk is to ensure minimal or no anticoagulant effect at the time of the procedure. ” It is interesting to note that a recent Letter to the Editor commented that our recommendation was quite conservative, that our goal was to “minimize the risk of hematologic complications to near zero. ” Douketis et al recommended that interruption should be based not only on half-lives but also on measured laboratory evidence. The DOACs generally have predictable pharmacokinetics and pharmacodynamics and usually do not require drug level monitoring. However, there are conditions such as hepatic or renal impairment or bleeding when the clinician needs to know whether the drug is present and at what level to make sound clinical decisions. Although ideal, this is not easily done. The tests for the DOACs are not routine coagulation tests and are not widely available. It is also not widely appreciated that each new DOAC requires an analyte-specific test; for example, the test for rivaroxaban will not give correctly calibrated results for apixaban. Setting up a new laboratory test, such as the antiFXa chromogenic assay for monitoring apixaban drug levels, includes testing analyte-specific calibration and quality controls, performing patient correlations with known samples, establishing standard operating procedures, training and development of test ordering in the laboratory information system, and notification of other departments including medical services and pharmacy. This process involves obtaining