How and when to measure anticoagulant effects of direct oral anticoagulants? Practical issues

Abstract

Direct oral anticoagulants (DOACs) do not require dose adjustment based on laboratory testing. However, it might be necessary to measure their plasma concentrations in the following specific situations: 1) before thrombolytic therapy in patients with stroke; 2) before surgery or invasive procedure; 3) in case of adverse events (thrombosis or hemorrhage); 4) when immediate reversal of anticoagulation is needed; 5) in patients with extreme body weight; 6) when administering additional drugs potentially interfering with DOACs; and 7) when overdosage is suspected regardless of concomitant bleeding. Basic coagulation tests, such as prothrombin and activated partial thromboplastin time, should not be used as standalone tests to assess the levels of anticoagulation as they are not specific for DOACs and their results are dependent on the type of reagent used for testing. Plasma DOAC concentrations should be assessed by dedicated tests: dilute thrombin time or ecarin tests (for dabigatran) or anti-factor Xa assays (for anti-factor Xa inhibitors). Dedicated tests should be calibrated against their respective plasma calibrators at certified DOAC concentrations and results should be expressed as ng/ml. Caution should be exerted when interpreting the results of the most common hemostatic parameters such as antithrombin, proteins C and S, lupus anticoagulant, or individual coagulation factors, as they may be strongly affected by the presence of a DOAC. Whenever possible, these parameters should be measured 4 to 5 days after discontinuation of DOAC anticoagulation.

Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants

“…The DOACs are currently administered at fixed doses without the need for laboratory testing and dose adjustments, except in some special clinical conditions . However, a high interindividual variability in drug plasma levels has been shown with all DOACs and an association between plasma levels and major events had been highlighted by FDA reports on DOAC phase III clinical studies…”

Bleeding in anticoagulated patients with atrial fibrillation: practical considerations

“…Of note, 15 patients died, including 13 patients following ICB (30--day mortality rate, 32%), whereas 2 patients include: 1) thrombolytic therapy in stroke, 2) surgery or invasive procedure, 3) a need for immediate reversal of anticoagulation, 4) extreme body weight, 5) substantial drug-drug interactions (eg, after transplantation, anti -HIV treatment), 6) suspected noncompliance or overdosage in case of thrombosis or hemorrhage, respectively. 97 Conclusions Overall, NOACs were comparable or superior to VKAs in most patients with AF as shown in RCTs and observational studies. Individualization of anticoagulant therapy based on benefit and safety profiles as well as patient characteristics should be considered in particular in patients with AF at elevated risk of bleeding, such as the elderly patients with several comorbidities and those with cancer (TABLE 2).…”

“…94 It has absolutely no possibility of any effect, but was given probably because many of these patients had a prolonged INR due to rivaroxaban. 97 Tranexamic acid, an antifibrinolytic agent effective in trauma or postpartum hemorrhages, acts as a lysine analog that impairs plasminogen activation on fibrin. In patients on NOACs, its efficacy is uncertain; however, it might be used.…”

Commentary: Should patients awaiting cardiac surgery who need anticoagulation be on direct oral anticoagulants or vitamin K antagonists?

“…DOACs have specific assays with specific reagents, and these are not readily available. 2,9 In addition, at present there are no standardized guidelines or therapeutic ranges established for what DOAC level to aim for particular operations. 2,9 Although reversal agents for DOACs are now on the market, there are issues with cost and efficacy.…”

“…2,9 In addition, at present there are no standardized guidelines or therapeutic ranges established for what DOAC level to aim for particular operations. 2,9 Although reversal agents for DOACs are now on the market, there are issues with cost and efficacy. 2,10 Even though there are problems with coumadin, such as need for monitoring, food/drug interactions, and nonstandardized dosing, some of these problems appear to be arising for DOACs as well.…”