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
1 . Makris M , van Veen JJ , Maclean R . Warfarin anticoagulation reversal : management of the asymptomatic and bleeding patient . J Thromb Thrombolysis 2010 ; 29:171 – 81 .
2 . Sherwood MW et al . Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin : ROCKET AF trial . J Am Coll Cardiol 2015 ; 66:2271 – 81 .
3 . Keeling D et al . Guidelines on oral anticoagulation with warfarin – fourth edition . Br J Haematol 2011 ; 154:311 – 24 .
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
Thromb Thrombolysis 2015 ; Dec 31 [ Epub ahead of print ].
5 . Refaai MA et al . Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal . Transfusion 2015 ; 55:2722 – 9 .
6 . Sarode R et al . Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding : a randomized , plasma controlled , phase IIIb study . Circulation 2013 ; 128:1234 – 43 .
7 . Goldstein JN et al . Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions : a phase 3b , open-label , non-inferiority , randomised trial . Lancet 2015 ; 385:2077 – 87 .
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 .
9 . Makris M et al . Guideline on the management of bleeding in patients on antithrombotic agents . Br J Haematol 2013 ; 160:35 – 46 .
10 . Kaatz S , Crowther M . Reversal of target specific oral anticoagulants . J Thromb Thrombolysis 2013 ; 36:195 – 202 .
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 .
9 www . hospitalpharmacyeurope . com