An update on laboratory assessment for direct oral anticoagulants (DOACs)

Abstract

The first direct oral anticoagulant (DOAC) to be approved for clinical use was dabigatran, a direct thrombin inhibitor, in 2010. Since that time, four additional DOACs, all direct anti‐Xa inhibitors, have been approved, including rivaroxaban, apixaban, edoxaban and betrixaban. Our knowledge about the effect of DOACs on laboratory testing, as well as the use of the laboratory for measuring DOACs has been an evolving process. These drugs are not routinely monitored in the same fashion as coumadin, but there is an increasing demand on the laboratory to have the capacity to adequately assess DOAC anticoagulant effect (pharmacodynamics) or levels (pharmacokinetics) in either emergent or the routine situations. This manuscript provides an update on laboratory guidance and progress of methods for measuring DOACs.

Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving Direct Oral AntiCoagulants

“…Nevertheless, DOAC interference cannot be entirely excluded, since it has been shown that false positive results may be observed in samples containing DOAC even at concentrations below the trough levels (i.e. DOAC plasma level just before the next intake of the drug) [22] or even at a level below the LLOQ of specific anti-Xa and dTT anti-IIa assays widely used in clinical laboratories may induce false positive results i.e around 20 ng/mL [7,23,24]. Owing to the high inter-individual variability of DOAC plasma level, a temporary interruption of DOAC treatment for 24 to 48 h or even longer could be required to ensure undetectable DOAC concentrations thus preventing false positive results [4,20,[25][26][27].…”

Comprehensive review of the impact of direct oral anticoagulants on thrombophilia diagnostic tests: Practical recommendations for the laboratory

“…C through , minimum plasma concentration during the dosing interval; C max , maximum plasma concentration during the dosing interval; VTE, venous thromboembolism; NVAF, non‐valvular atrial fibrillation; OD, once daily; bid, twice daily; APC‐R, activated protein C resistance. Notes: Data on plasma concentrations were extracted from Douxfils et al and Gosselin et al 2,4,7,9,10 for apixaban, edoxaban, rivaroxaban and from Siriez et al 8 for betrixaban…”

“…These DOAC concentrations may not be reflective of all reagents or methods. Notes: Data on plasma concentrations were extracted from Douxfils et al, 11 Favaloro et al, 1 Gessoni et al, 35 Bonar et al 12 and Gosselin et al 2 …”

“…Since approximately 10 years, direct oral anticoagulants (DOACs) were approved for several thromboembolic disorders 1 . The key advantages of these anticoagulants are the absence of routine monitoring, an oral administration with fixed doses and more predictable pharmacokinetic profiles 1‐3 . Nevertheless, although the clinical usefulness of blood measurements to assess the level of DOACs anticoagulation is subject to debate in the literature, clinicians and scientists agree that there is a laboratory and clinical need to know the impact of these anticoagulants on diagnostic tests to avoid misinterpretation of results 1,3‐6 .…”

Effect of Multiple Freeze–Thaw Cycles on Coagulation Testing

“…What is encouraging is the increasing number of publications that are describing freeze-thaw effects (e.g., of direct oral anticoagulant levels), with typically no adverse effect of up to three freeze-thaw cycles being reported. 6 What should be considered when performing any freeze-thaw study is the continuity of the thawing and testing process, as standardization will help avoid biases, particularly with fibrinogen and FVIII testing. 7 Critically, the ability to utilize previously thawed samples may alleviate some challenges with algorithmic testing, as well as with preservation for biorepository purposes.…”