Anticoagulant Reversal Handbook - Page 11

Overview be dialysed out if the facilities for its rapid set-up are available ; in practice , this is not a realistic possibility for most hospitals . If more rapid reversal is required , this can only be achieved with the use of activated or non-activated PCCs .
A large number of publications have reported on the use of PCC to reverse DOACs . Most publications centre around the in vitro and ex vivo reversal or the use of animal models of bleeding . Very few case reports of the use of PCC to reverse DOAC-related bleeding in humans have been published , and these reports suffer from publication bias . The laboratory studies involve the addition of exogenous PCC to anticoagulated samples and measuring either the prothrombin time or activated partial thromboplastin time or , more commonly , thrombin generation to demonstrate improvement in the results . There are many ways of performing thrombin generation and the results of even similar experiments are not always consistent . There are a large number of reports of PCC use in animal bleeding models , with many animals and many models used . In general , the results show that PCCs do , at least partially , reverse the coagulopathy and reduce the bleeding . Their success appears to be greater for the Xa than the IIa inhibitors .
Human data on the use of PCC to reverse DOACs can be subdivided in that from non-bleeding human volunteers who take the DOAC and then receive the PCC , or a limited number of uncontrolled case reports where bleeding humans receive PCC . There are many unanswered question on the use of PCC to reverse DOAC-related bleeding but , for now , they appear to be the best widely available drugs that we have . 12
Conclusions It is often assumed that when specific reversal agents for the IIa and Xa inhibitors are introduced , there will no longer be a role for PCC for DOAC reversal ; but we believe that this is a premature assumption . Experience suggests that any newly introduced drug with a limited sales market will be very expensive and certainly much more expensive than PCC . A further advantage of PCC is where the patient ’ s history is unreliable as to which DOAC is being taken , because PCCs are at least partially effective in the reversal of all DOACs . l
References
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4 . Morgan Jones G et al . 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal in severe bleeding : A multicenter retrospective , propensity-matched pilot study . J
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8 . Milling TJ et al . Thromboembolic events after vitamin K antagonist reversal with 4-factor Prothrombin Complex Concentrate : exploratory analyses of two randomized , plasma controlled studies . Ann Emerg Med 2016 ; 67:96 – 105 .
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11 . Kitchen S et al . Measurement of non-coumarin anticoagulants and their effects on tests of haemostasis : Guidance from the British Committee for Standards in Haematology . Br J Haematol 2014 ; 166:830 – 41 .
12 . Makris M . Prothrombin complex concentrate for non-vitamin K oral anticoagulant reversal : good enough for now ? J Thromb Haemost 2014 ; 12 : 1425 – 7 .
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