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1/ Antidote news! There has been promise recently regarding antidotes being developed for DOACs. Before we get onto that, a quick summary of what we have so far...
2/ In the case of bleeding while on warfarin, this should be stratified by severity. Usual rule is if life/limb/sight threatening bleeding, prothrombin complex concentrate + vit K is used. If not, vitamin K +- pause/cessation of warfarin is advised.
3/ Warfarin works by inhibiting vitamin K-dependent clotting factor production. These factors are II, VII, IX and X. The 'antidote' is prothrombin complex concentrate (e.g beriplex) which is a concentrated 'soup' of factors II, VII, IX and X (and some protein C and S)
4/ So a fairly straightforward replacement of 'missing' factors. The effect lasts ~6 hours, hence the need for vit K as well so the liver can start making clotting factors again. Without it, the bleeding risk will return. There is a small risk of thrombosis associated with PCC
5/ Dabigatran is a direct thrombin inhibitor, not used as commonly as anti-Xa agents (rivaroxaban etc). Idarucizumab is the 'antidote' and is a small molecule which binds dabigatran, with no prothrombotic activity itself. V effective. See NEJM ref https://www.nejm.org/doi/full/10.1056/NEJMoa1502000
6/ Andexanet is an 'antidote' for the anti-Xa agents (specifically rivaroxaban and apixaban in the FDA approval 2018). It was sped through approval due to the huge demand. It is available in the US, but was not recommended by NICE due to limited evidence of efficacy over...
7/ .. PCC which is often used in the context of bleeding on anti-Xa agents, even though it is not a formal antidote, rather an infusion of activated clotting factors. At a cost of ÂŁ15k per dose at list price, cost effectiveness could not be assured. https://www.nice.org.uk/guidance/gid-ta10440/documents/129
8/ *Note the Scottish medicines consortium has recently approved andexanet for uncontrolled/life-threatening bleeding on rivaroxaban or apixaban.* A paper released last month has shown significant concern about the efficacy of andexanet in a retrospective observational report...
9/ Numbers were small (n=21) but anticoagulation reversal was deemed 'effective' in only 47.6%, and poor in 52.8%. 8 patients died, and a further 6 patients had ischaemic complications, both arterial and venous.
10/ Thrombosis is known to be more common in patients with haemorrhage but an incidence of over 25% is concerning. Authors advise further investigation of these results. https://onlinelibrary.wiley.com/doi/10.1111/jth.15031 @JTHjournal #blooducation #anticoagulation #FOAMed
11/ #BukuHaematology contains FAQs about DOACs, and the Northern region warfarin reversal guidelines for our users in the North-East of England @NewcastleHosps @QEGateshead @NorthumbriaNHS @STSFTrust
