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Direct Oral Anticoagulants: Reversal Strategies for DOACs & Laboratory Role

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Pearls of Laboratory Medicine are peer-reviewed presentations focused on a specific test or disease area relevant to contemporary laboratory medicine and pathology.

Welcome to this pearl of laboratory medicine brought to you by aacc and the clinical chemistry trainee council view this and many more pearls as well as other free educational material at hello my name is bob gosselin i currently serve as a volunteer with uc davis thrombosis hemostasis center after my retirement in 2017 from the university health

System as a senior clinical laboratory scientist in special coagulation welcome to this pearl vibratory medicine on doe x reversal strategies for doax is their laboratory rule this program was created with dr dot adcock the chief medical officer and senior vice president of labcorp this session is a combined effort between the american association for clinical

Chemistry and the north american specialized coagulation laboratory association first doak the big trend or pradaxa as it’s known was approved for use in the united states in 2010. the next several years factor 10a doax including rivaroxaban apixaban were approved for use in the early years there were no specific reversal agents or antidotes for these drugs to

Neutralize dabigatran activate charcoal could be used if recently ingested or dialysis to physically remove the drug other traditional means of reversing anticoagulants such as fresh frozen plasma or activated factor 7a have limited efficacy for factor 10a doe x the reversal strategies include activated factor 7a prothrombin complex concentrates or pccs in both

Activated or inactivated forms in 2015 pracspine was fda approved as a specific reversal agent for dubigatran in 2018 andexo was fda approved as a specific reversal agent for rivaroxaban and apixaban however the use of activated non-activated pccs are still being used for doak reversal while the primary limited to factor 10a delax the clinical indications for

Dolac reversal include hemorrhage or major bleeding especially into critical organs or spaces the need for emergent invasive procedures or reducing drug exposure prior to thrombolysis and acute thrombotic stroke additionally it has been proposed that de montreal doak level should be present prior to using reversal agents a particular note that safe or acceptable

Doeag thresholds or levels for emergent invasive procedures of thrombolysis is based on limited data as a reminder the direct targets are represented in this cartoon of the simplified coagulation cascade the bigatran currently the only direct thrombin doak inhibits thermometer factor 2a the factor 10a doeag includes river oxaban apixaban didoxaband and betryxaban

And inhibit factor 1a in the common pathway using the same coagulation cartoon the specific reversal strategies or factor supplements such as pccs will be detailed practifying targets dubigatran and thrombin index of targets factor 10a doe x and factor 10a fiba targets will add mostly factor 7a but also factor 9 factor 10 and factor 2 or per thrombin profile9

Is a three factor pcc and we’ll add factor nine factor ten and prothrombin k centra is a four factor pcc and we’ll add factor seven factor nine factor ten and prothrombin prank spine or i dare you sumab from bearing your eagle act is a humanized monoclonal antibody fragment derived from igg-1 molecule the current dose consists of two separate 2.5 gram doses

That will bind to both the bigatran and its acetyl glutaronicide metabolites a single five gram dose of fine will neutralize up to 1 000 nanograms of the bigatran but drug rebound or reappearance has been noted in some patients 12 to 24 hours after treatment a particular note for the laboratory prakaxvine does not have any thermogenicity or ability to generate

Clots but will correct prolongation of the pt apdt thrombin time dilute thrombin and echoing clotting times due to the bigatran these tests may also detect the reappearance of the drug although the more sensitive methods such as drug calibrated economy-based or anti-factor ii aises to assess post-prac spine treatment efficacy may be warranted especially if the

Patient’s pre-treatment levels exceed one thousand nanograms per ml partial or incomplete correction of screening assay such as the pt or a ptt after pac spine treatment would suggest either concomitant coagulopathy such as a factor deficiency or inhibitor or pre-treatment big trend concentrations of greater than one thousand nanograms per ml indexa or indexing

Alpha from portola pharmaceuticals is a recombinant and activated factor 10a this drug is currently only fda approved for river oxbane and apixaban reversal there are two doses for indexa the low dose consisting of 400 milligrams of the drug and the higher 800 milligram dose it has been demonstrated that index opposes some thromogenicity by reducing tissue factor

Pathway inhibitor or tfpi and increasing thrombin generation for laboratory considerations the efficacy of indexa can be measured using anti-tenant analyses as indexa will reduce anti-tenant levels whether those tests are doak or heparin calibrated the initial portola study suggested a rebound in anti-dna activity after cessation of index infusion but it was later

Determined that the laboratory method they use had a high sample pre-dilution about 1-30 which created an in-vitro dissociation of the drug and substrate when lower sample pre-dilutions for example 1-4 were used no anti-10 a rebound was observed there are no fda recommendations for measuring anti-dna before or after index of treatment with doses predicated on

The last known exposure or dose and if that is unknown to used a higher dose of 800 milligrams fiba or factory bypassing agent from buxalto was initially approved in 1986 for use of treatment of hemophilia a patient with inhibitors this product is also described as an activated protroman complex concentrate and contains mostly activated factor 7 with non-activated

Factors 9 10 and prothrombin there are case reports of fever use in doac reversal as fibo was used in hemophilia a patients with inhibitors the apdt was a common measurement to detect drug efficacy with a reduction in apdt if the treatment was working as this product contains factors 2 and 10 it is presumed that the pt will correct that these factors are sufficient

Or if do act to either thrombin or factor 10a are present however there is unclear utility of the laboratory in assessing fiba efficacy in factor 10a do act reversal profile9 is a three factor pcc from grippers biologics this is a lyophilized product containing inactivated factors 2 9 and 10. prophylmine is fda approved for use in the treatment of hemophilia b

Patients with case reports for use in both doac and warfarin reversal as profile 9 contains factors 2 9 and 10 this product would presumably correct the pt and abt due to deficiencies or inhibitors to these factors at this time there is unclear utility of the use of these tests for assessing prophyline reversal of factor 10a doe x kcentra is a four factor pcc from

Csl bearing containing non-activated factors 2 7 9 and 10. the current fda indications for casentra is for reversal of vitamin k dependent pro coagulant factors 2 7 9 and 10 induced by oral vitamin k antagonists such as warfarin or coumadin there are case reports of case sentry use in factor 10 a doe act reversal for laboratory considerations and case central

Use as this product contains factors 2 7 9 and 10 this drug would presumably correct the pt and or aptt due to deficiencies or inhibitors to these factors at this time there is unclear utility of the laboratory or laboratory tests in assessing case center use for factor 10a doak reversal at this point we would like to caution using low liquid heparin values

For estimating factor 10a doe at concentration as these tests have been reported for use in determining acceptability and avoidance for thrombolysis and acute stroke the first premise is that a low liquid heparin is 0.1 units per ml can reliably determine relatively low concentrations of factor 10a doe x with the general acceptability that the lower limit of

Quantitation or lloq can assure less than 30 to 50 nanogards per ml the factor 10a doex which is generally a true statement the second premise is that all the place should be avoided due to high douat concentrations of greater than 50 0.5 international units per ml which again is also generally a true statement however conversely the less than 0.5 international

Units per ml threshold should would not be an appropriate threshold if the acceptable safe factor 108 doe concentration is less than 50 nanograms per amount to summarize for the bigatron prakspine is generally accepted as the ideal choice for reversal for factor 10a dox this is less certain as the cost of indexa has led to less universal acceptance for the use

Of this reversal agent the low dose cost for indexa is estimated to be about 25 000 whereas the high dose estimates to be about 40 000 there are published reports and institutional experience about the efficacy of pccs season factor 108 doe act reversal there are currently no laboratory recommendations for doac reversal but our institutional experience suggests

That providing a pre-treatment do act level will assist the clinical staff in pcc dosing importantly the laboratory should verify the local use of heparin calibration anti-10 a testing if such tests are used for factor 10a doac estimation and verify locally any clinician threshold used to determine safe intervention or reversal strategies in doac anticoagulated

Patients and thank you uh for joining me on this pearl laboratory medicine on reversal strategies for doe x is their laboratory role for more like this as well as articles podcasts and more please visit the trainee council at

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Direct Oral Anticoagulants: Reversal Strategies for DOACs & Laboratory Role By AACC