Pre-operative reversal
24 should be administered concomitantly to sustain the effects of PCC . 18 In the case of intracranial haemorrhage , clinicians are unlikely to resume VKA therapy in the following two to four weeks after the event . Hospitals should have their own protocols regarding dosage , but these patients can receive a dose of 10mg IV vitamin K concomitantly with PCC , without concern for VKA refractoriness . Other patients requiring emergent major surgery may receive 3 – 5mg IV vitamin K , or 1 – 2mg IV in patients with a mechanical heart valve or LVAD . Concomitant vitamin K need not be given to patients undergoing INR reversal with PCC for minor invasive procedures .
Dosing of PCC for minor surgery and minor invasive procedures For patients undergoing minor surgeries or invasive procedures , such as line placement or thoracentesis , or for patients with LVAD or a mechanical heart valve , a higher INR goal of ≤2.0 may be used . Given the low added bleeding risk of many minor invasive procedures , there is evidence to support that they may be performed safely without any prior correction of INR . 23 However , if pre-procedure 4F-PCC is deemed necessary , a single low , fixed dose of 500 or 1000IU PCC will often achieve this goal , and concomitant vitamin K need not be given .
Conclusions In summary , VKA reversal is often required prior to surgery or invasive procedures to avoid excessive bleeding associated with anticoagulation . The urgency and bleeding risk of the procedure , as well as the patient-specific thromboembolic risk of VKA cessation , often determines the desired post-reversal INR and options for VKA reversal . In patients requiring major surgery , an INR of ≤1.5 should be achieved , but a higher INR goal of ≤2.0 may be used in patients undergoing minor surgeries or invasive procedures . Pre-operative management of VKA reversal can be accomplished using IV vitamin K administration and / or appropriate dose of 4F-PCC , and the VKA reversal method used depends on the type and urgency of surgical invention . If 4F-PCC is unavailable , then plasma can be used with the understanding that a large volume may have to be given , resulting in a much slower rate of VKA reversal . l
References 1 . Hirsh J et al . American Heart Association /
American College of Cardiology foundation guide
Table 2 : 4F-PCC dosing for VKA reversal
Pre-treatment INR Dosage based on patient weight ( IU / kg )
2 to < 4 25 4 – 6 35 > 6 50
* Up to a maximum 100kg ; IU , international units
to warfarin therapy . Circulation 2003 ; 107 ( 12 ): fractionatedplasmaproducts / ucm221726 . htm
1692 – 711 .
( accessed June 2016 ). 2 . Burbury KL et al . Short-term warfarin reversal for 12 . Profilnine SD - Factor IX complex . www . fda . gov / elective surgery – using low-dose intravenous biologicsbloodvaccines / bloodbloodproducts / vitamin K : Safe , reliable and convenient . Br J approvedproducts / licensedproductsblas /
Haematol 2011 ; 154 ( 5 ): 626 – 34 . fractionatedplasmaproducts / ucm261884 . htm
3 . Douketis JD et al . Perioperative management of ( accessed June 2016 ). antithrombotic therapy . Antithrombotic therapy 13 . Kcentra ( Prothrombin Complex Concentrate , and prevention of thrombosis , 9th ed : American Human ). www . fda . gov / biologicsbloodvaccines / College of Chest Physicians evidence-based bloodbloodproducts / approvedproducts / clinical practice guidelines . Chest 2012 ; 141 ( 2 licensedproductsblas /
Suppl ): e326S – e350S . fractionatedplasmaproducts / ucm350130 . htm
4 . Healey JS et al . Periprocedural bleeding and ( accessed June 2016 ). thromboembolic events with dabigatran 14 . Voils SA , Baird B . Systematic review : 3-factor compared with warfarin : Results from the versus 4-factor prothrombin complex randomized evaluation of long-term concentrate for warfarin reversal : Does it matter ? anticoagulation therapy ( RE-LY ) randomized trial . Thromb Res 2012 ; 130 ( 6 ): 833 – 40 . Circulation 2012 ; 126 ( 3 ): 343 – 8 .
15 . Voils SA et al . Comparative effectiveness of
5 . Olesen JB et al . Validation of risk stratification 3- versus 4-factor prothrombin complex schemes for predicting stroke and concentrate for emergent warfarin reversal . thromboembolism in patients with atrial Thromb Res 2015 ; 136 ( 3 ): 595 – 8 . fibrillation : nationwide cohort study . BMJ 16 . Mangram A et al . Is there a difference in efficacy ,
2011 ; 342 : d124 . safety , and cost-effectiveness between 3-factor
6 . Kovacs MJ et al . Single-arm study of bridging and 4-factor prothrombin complex concentrates therapy with low-molecular-weight heparin for among trauma patients on oral anticoagulants ? patients at risk of arterial embolism who require J Crit Care 2016 ; 33:252 – 6 . temporary interruption of warfarin . Circulation 17 . Hanley JP . Warfarin reversal . J Clin Pathol 2004 ; 110 ( 12 ): 1658 – 63 .
2004 ; 57 ( 11 ): 1132 – 9 .
7 . Douketis JD et al . Perioperative bridging
18 . CSL Behring . [ Package insert ] Kcentra anticoagulation in patients with atrial fibrillation . Prothrombin Complex Concentrate ( Human ). N Engl J Med 2015 ; 373:823 – 33 .
2013 . 8 . Watson HG et al . A comparison of the efficacy 19 . Butler J . Use of low-dose prothrombin complex and rate of response to oral and intravenous concentrate before lumbar puncture . Am J Heal vitamin K in reversal of over-anticoagulation with Pharm 2015 ; 72 ( 3 ): 203 – 5 . warfarin . Br J Haematol 2001 ; 115 ( 1 ): 145 – 9 . 20 . Quick JA , Meyer JM , Coughenour JP . Less is
9 . Kinard TN , Sarode R . Four factor prothrombin more : Low-dose Prothrombin Complex complex concentrate ( human ): review of the Concentrate effective in acute care surgery pharmacology and clinical application for patients . Am Surg 2015 ; 81 ( 6 ): 646 – 50 . vitamin K antagonist reversal . Expert Rev 21 . Varga C et al . The effectiveness and safety of
Cardiovasc Ther 2014 ; 12 ( 4 ): 417 – 27 . fixed low-dose prothrombin complex
10 . Goldstein JN et al . Four-factor prothrombin concentrates in patients requiring urgent complex concentrate versus plasma for rapid reversal of warfarin ( CME ). Transfusion vitamin K antagonist reversal in patients needing 2013 ; 53 ( 7 ): 1451 – 8 . urgent surgical or invasive interventions : A phase 22 . Sarode R et al . Rapid warfarin reversal : a 3b , open-label , non-inferiority , randomised trial . 3-factor prothrombin complex concentrate and Lancet 2015 ; 385 ( 9982 ): 2077 – 87 . recombinant factor VIIa cocktail for intracerebral
11 . FEIBA NF ( Anti-inhibitor coagulant complex ). hemorrhage . J Neurosurg 2012 ; 116 ( 3 ): 491 – 7 . www . fda . gov / biologicsbloodvaccines / 23 . Puchalski JT et al . The safety of thoracentesis in bloodbloodproducts / approvedproducts / patients with uncorrected bleeding risk . Ann Am licensedproductsblas / Thorac Soc 2013 ; 10 ( 4 ): 336 – 41 . www . hospitalpharmacyeurope . com