Reversal of warfarin era thinking

Shatzel, Joseph J.; Daughety, Molly M.; Prasad, Vinay; DeLoughery, Thomas G.

doi:10.1111/joim.12697

Cited by 5 publications

(7 citation statements)

References 10 publications

(15 reference statements)

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“…DOACs have relatively short half‐lives, but we do not currently have rapid tests to measure the level of DOAC effects as we do with warfarin. This is evidenced by the fact that nearly a quarter of patients in DOAC reversal studies did not have detectable drug levels in their system in hindsight . It is likely that many of the patients in our study with DOAC‐associated bleeding were not anticoagulated by the time reversal was given, while all of the patients who received 4F‐PCC for warfarin in our study had elevated INRs.…”

Section: Resultsmentioning

confidence: 87%

“…This is evidenced by the fact that nearly a quarter of patients in DOAC reversal studies did not have detectable drug levels in their system in hindsight. 14 It is likely that many of the patients in our study with DOAC-associated bleeding were not anticoagulated by the time reversal was given, while all of the patients who received 4F-PCC for warfarin in our study had elevated INRs. Other studies have suggested that patients with DOACassociated major bleeding inherently have better outcomes than those with warfarin-associated major bleeding.…”

Section: Re Sults/discussionmentioning

confidence: 84%

See 1 more Smart Citation

Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Scharman

Shatzel

Kim

et al. 2018

European J of Haematology

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Section: Resultsmentioning

confidence: 87%

Section: Re Sults/discussionmentioning

confidence: 84%

Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Scharman

Shatzel

Kim

et al. 2018

European J of Haematology

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“…In addition, there is a need for regular therapeutic drug monitoring with control of the international normalized ratio (INR) indicator at a safe level within two or three times, which entails additional economic burdens on health systems [ 8 ]. A significant disadvantage of this group of drugs is the irreversibility of the drug in the event of an overdose [ 9 ]. The deviation of the INR from the permissible limits, both in the lower and in higher directions, is prognostically unfavorable.…”

Section: Introductionmentioning

confidence: 99%

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions

et al. 2021

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Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

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“…Also, there is a need for regular therapeutic drug monitoring with the control of international normalized ratio (INR) indicator at safe level within 2-3, which entails additional economic burdens on health system [8]. A significant disadvantage of this group of drugs is irreversibility of drug in the event of an overdose [9]. The deviation of the INR from the permissible limits, both in lower and in higher direction, is prognostically unfavorable indicator.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of Direct Oral Anticoagulants

Shnayder¹,

Петрова²,

Bochanova³

et al. 2021

Pharmacogenetics

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For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.

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Reversal of warfarin era thinking

Cited by 5 publications

References 10 publications

Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions

Pharmacogenetics of Direct Oral Anticoagulants

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