Warfarin is a commonly prescribed anticoagulant that may, in selected situations, require rapid reversal of its effects. Several approaches to achieve reversal have been explored, including the administration of prothrombin complex concentrates (PCCs), Many factors can influence determination of an appropriate PCC dose and the resulting effects. Considerations on the use of PCC products to expedite the reversal of warfarin are described.
LeviM. Emergency reversal of antithrombotic treatment. Intern Emerg Med2009; 4:137–45. DOI 1007/s11739-008-0201-8
2.
ChapmanSA, IrwinED, BealA, KulinskiN, HutsonK, ThorsonMAL. Prothrombin complex concentrate versus standard therapies for INR reversal in trauma patients receiving warfarin anticoagulation. Ann Pharmacother2011; 45:869–75. DOI 10.1345/aph.1P605
3.
BaglinTP, KeelingDM, WatsonHG. Guidelines on oral anticoagulation (warfarin): third edition—2005 update. Br J Haematol2006; 132:277–85. DOI 10.1111/j.1365-2141.2005.05856.x
4.
AnsellJ, HirshJ, HylekE, JacobsonA, CrowtherM, PalaretiG. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest2008; 133:160S–98S. DOI 10.1378/chest.08-0670
5.
FurieKL, KasnerSE, AdamsRJ. American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke2011; 42:227–76. DOI 10.1161/STR.0b013e3181f7d043
6.
PernodG, GodierA, GozaloC, TremeyB, SieP. French clinical practice guidelines on the management of patients on vitamin K antagonists in at-risk situations (overdose, risk of bleeding, and active bleeding). Thromb Res2010; 126:e167–74. DOI 10.1016/j.thromres.2010.06.017
7.
BakerRI, CoughlinPB, GallusAS, HarperPL, SalemHH, WoodEM; Warfarin Reversal Consensus Group. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust2004; 181:492–7.
8.
PrestonFE, LaidlawST, SampsonB, KitchenS. Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients. Br J Haematol2002; 116:619–24.
9.
KhorsandN, VeegerNJ, MullerM. Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy. Transfus Med2011; 21:116–23. DOI 10.1111/j.1365-3148.2010.01050.x
10.
van AartL, EijkhoutHW, KamphuisJS. Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial. Thromb Res2006; 118:313–20. DOI 10.1016/j.thrombres.2005.08.005
11.
BershadEM, SuarezJI. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care2010; 12:403–13. DOI 10.1007/s12028-0079310-0
12.
VangML, HvasAM, RavnHB. Urgent reversal of vitamin K antagonist therapy. Acta Anaesthesiol Scand. Epub March 21, 2011. DOI 10.1111/j.1399-6576.2011.02414.x
13.
HollandL, WarkentinTE, RefaaiM, CrowtherMA, JohnstonMA, SarodeR. Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion2009; 49:1171–7. DOI 10.1111/j.1537-2995.2008.02080.x
14.
CrawfordJH, AugustsonBM. Prothrombinex use for the reversal of warfarin: is fresh frozen plasma needed?Med J Aust2006; 184:365–6.
15.
GodierA, SusenS, SamamaCM. Treatment of massive bleeding with prothrombin complex concentrate: argument against. J Thromb Haemost2010; 8:2592–5. DOI 10.1111/j.1538-7836.2010.04062.x
16.
WójcikC, SchymikML, CureEG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med2009; 2:217–25. DOI 10.1007/s12245-009-0125-8
17.
Desmurs-ClavelH, HuchonC, ChatardB, NegrierC, DargaudY. Reversal of the inhibitory effect of fondaparinux on thrombin generation by rFVIIa, aPCC and PCC. Thromb Res2009; 123:796–8. DOI 10.1016/j.thrombres.2008.07.007
18.
PabingerI, TiedeA, KalinaU, KnaubS, GermannR, OstermannH; Beriplex P/N Anticoagulation Reversal Study Group. Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate: a prospective clinical trial of emergency anticoagulation reversal. Ann Hematol2010; 89:309–16. DOI 10.1007/s00277-009-0830-7
19.
GroblerC, CallumJ, McCluskeySA. Reversal of vitamin K antagonists prior to urgent surgery. Can J Anaesth2010; 57:458–67. DOI 10.1007/s12630.009-9250-3
20.
MorimotoY, NiwaH, NakataniT. On the use of prothrombin complex concentrate in patients with coagulopathy requiring tooth extraction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2010; 110:e7–10. DOI 10.1016/j.tripleo.2010.08.014
21.
ImbertiD, BarillariG, BiasioliC. Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage. Blood Transfus2011; 9:48–55. DOI 10.2450/2011.0065-10
22.
TranH, CollecuttM, WhiteheadS, SalemHH. Prothrombin complex concentrates used alone in urgent reversal of warfarin anticoagulation. Intern Med J2010; 41:337–43. DOI 10.111/j.1445-5994.2010.02237.x
23.
YasakaM, SakataT, NaritomiH, MinematsuK. Optimal dose of prothrombin complex concentrate for acute reversal of anticoagulation. Thromb Res2005; 115:455–9. DOI 10.1016/j.thrombres.2004.09.002
24.
MakrisM, van VeenJJ, MacleanR. Warfarin anticoagulation reversal: management of the asymptomatic and bleeding patient. J Thromb Thrombolys2010; 29:171–81. DOI 10.1007/s11239-009-0412-5
25.
GoodnoughLT, ShanderA. How we treat management of warfarin-associated coagulopathy in patients with intracerebral hemorrhage. Blood2011; 117:6091–9. DOI 10.1182/blood-2010-11-316075
26.
HuttnerHB, SchellingerPD, HartmannM. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke2006; 37:1465–70. DOI 10.1161/01.STR.0000221786.81354.d6
27.
MayerSA, BrunNC, BegtrupK. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med2008; 358:2127–37. DOI 10.1056/NEJMoa0707534
28.
DickneiteG, DörrB, KaspereitF, TanakaKA. Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model. J Trauma2010; 68:1151–7. DOI 10.1097/TA.0b013e3181b06364
29.
BershadEM, FarhadiS, SuriMF. Coagulopathy and inhospital deaths in patients with acute subdural hematoma. J Neurosurg2008; 109:664–9. DOI 103171/JNS/2008/109/10/0664
30.
KuwashiroT, YasakaM, ItabashiR. Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage. Cerebrovasc Dis2011; 31:170–6. DOI 10.1159/000321766
31.
ChongCT, LewTW, KuperanP, TanJJ, TanHL, KwekTK. Rapid reversal of coagulopathy in warfarin-related intracranial haemorrhages with prothrombin complex concentrates. Anaesth Intensive Care2010; 38:474–80.
32.
DemeyereR, GillardinS, ArnoutJ, StrengersPF. Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study. Vox Sang2010; 99:251–60. DOI 10.1111/j.1423-0410.2010.01339
33.
SteibA, BarreJ, MertesM. Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists?J Thromb Haemost2010; 8:499–503. DOI 10.1111/j.1538-7836.2009.03685.x
34.
SchickKS, FertmannJM, JauchKW, HoffmannJN. Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care2009; 13:R191. DOI 10.1186/cc8186
35.
NishijimaDK, DagerWE, SchrotRJ, HolmesJF. The efficacy of factor VIIa in emergency department patients with warfarin use and traumatic intracranial hemorrhage. Acad Emerg Med2010; 17:244–51. DOI 10.1111/j.1553-2712.2010.00666.x
36.
RizosT, JenetzkyE, HerwehC. Point-of-care reversal treatment in phenprocoumon-related intracerebral hemorrhage. Ann Neurol2010; 67:788–93. DOI 10.1002/ana21965
