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Stroke Note

Free Access

Reversal of Warfarin Anticoagulation with Prothrombin Complex Concentrate before Thrombolysis for Acute Stroke

Jalini S. · Jin A.Y. · Taylor S.W.

Author affiliations

Division of Neurology, Queens University, Kingston, Ont., Canada

Corresponding Author

Sean W. Taylor

Connell 7 Kingston General Hospital

76, Stewart Street

Kingston, ON K7L 2V7 (Canada)

Tel. +1 613 549 6666, ext. 2472, E-Mail taylors1@kgh.kari.net

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Cerebrovasc Dis 2012;33:597

An 84-year-old woman with myasthenia gravis and atrial fibrillation presented with impaired consciousness, neglect, left hemianopsia, hemiplegia and hemianesthesia [National Institutes of Health Stroke Scale (NIHSS) score 24]. Imaging at 50 min showed right middle cerebral artery (MCA) thrombus, but no ischemic change (fig. 1a, b). She was taking warfarin [international normalized ratio (INR) 2.0], precluding thrombolysis. Mechanical revascularization was unavailable hence consent was obtained to reverse anticoagulation with prothrombin complex concentrate (PCC). Fifteen minutes after PCC (40 ml dose, 1,000 IU factor IX activity), the INR was 1.2 and i.v. tissue plasminogen activator (tPA) was administered. Computed tomography (CT) at 24 h showed thrombus resolution and infarct limited to the lentiform nucleus with no filling defect on CT angiogram (fig. 1c, d). She was discharged at day 7 to a rehabilitation center (NIHSS score 6). At 8 weeks, her NIHSS score was 4.

Fig. 1

a Proximal right MCA hyperdensity (arrow) indicating acute thrombus. b No acute ischemic parenchymal change on admission. c CT angiography showing resolution of right MCA occlusion on day 1. d Small infarct in the right posterior lentiform nucleus on day 1 (arrowhead).

http://www.karger.com/WebMaterial/ShowPic/204172

PCC contains factors II, VII, IX, X, protein C and protein S and causes rapid reversal of warfarin-induced coagulopathy [1]. Routine use of PCC in acute stroke is not recommended due to the thrombotic risk estimated between 1–2% [2]. However, proximal MCA occlusions are unlikely to recanalize spontaneously, and outcome following persistent occlusion is poor. PCC has been used to reverse warfarin-associated coagulopathy prior to tPA in animal models [3] and may reduce secondary hemorrhagic transformation [4]. Recombinant factor VIIa has been used in similar situations in humans [5], but carries a greater thrombotic risk [6] and is less effective for hemostasis [7], making PCC a potentially favorable option.


References

  1. Leissinger CA, Blatt PM, Hoots WK, Ewenstein B: Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 2008;83:137–143.
  2. Dentali F, Marchesi C, Pierfranceschi MG, Crowther M, Garcia D, Hylek E, Witt DM, Clark NP, Squizzato A, Imberti D, Ageno W: Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost 2011;106:429–438.
  3. Sun L, Zhou W, Ploen R, Heiland S, Zorn M, Veltkamp R: Rapid reversal of anticoagulation prevents excessive secondary hemorrhage after thrombolysis in a thromboembolic model in rats. Stroke 2011;42:3524–3529.
  4. Pfeilschifter W, Spitzer D, Pfeilschifter J, Steinmetz H, Foerch C: Warfarin anticoagulation exacerbates the risk of hemorrhagic transformation after rt-PA treatment in experimental stroke: therapeutic potential of PCC. PLoS One 2011;6:e26087.
  5. Talkad A, Mathews M, Honings D, Jahnel J, Wang D: Reversal of warfarin-induced anticoagulation with factor VIIa prior to rt-PA in acute stroke. Neurology 2005;64:1480–1481.
  6. Levi M, Levy JH, Andersen HF, Truloff D: Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010;363:1791–1800.
  7. Dickneite G, Dorr B, Kaspereit F, Tanaka KA: Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model. J Trauma 2010;68:1151–1157.

Author Contacts

Sean W. Taylor

Connell 7 Kingston General Hospital

76, Stewart Street

Kingston, ON K7L 2V7 (Canada)

Tel. +1 613 549 6666, ext. 2472, E-Mail taylors1@kgh.kari.net


Article / Publication Details

Published online: June 14, 2012
Issue release date: June 2012

Number of Print Pages: 1
Number of Figures: 1
Number of Tables: 0

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: http://www.karger.com/CED


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References

  1. Leissinger CA, Blatt PM, Hoots WK, Ewenstein B: Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 2008;83:137–143.
  2. Dentali F, Marchesi C, Pierfranceschi MG, Crowther M, Garcia D, Hylek E, Witt DM, Clark NP, Squizzato A, Imberti D, Ageno W: Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost 2011;106:429–438.
  3. Sun L, Zhou W, Ploen R, Heiland S, Zorn M, Veltkamp R: Rapid reversal of anticoagulation prevents excessive secondary hemorrhage after thrombolysis in a thromboembolic model in rats. Stroke 2011;42:3524–3529.
  4. Pfeilschifter W, Spitzer D, Pfeilschifter J, Steinmetz H, Foerch C: Warfarin anticoagulation exacerbates the risk of hemorrhagic transformation after rt-PA treatment in experimental stroke: therapeutic potential of PCC. PLoS One 2011;6:e26087.
  5. Talkad A, Mathews M, Honings D, Jahnel J, Wang D: Reversal of warfarin-induced anticoagulation with factor VIIa prior to rt-PA in acute stroke. Neurology 2005;64:1480–1481.
  6. Levi M, Levy JH, Andersen HF, Truloff D: Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010;363:1791–1800.
  7. Dickneite G, Dorr B, Kaspereit F, Tanaka KA: Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model. J Trauma 2010;68:1151–1157.
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