Reversal of warfarin-induced anticoagulation with factor VIIa prior to rt-PA in acute stroke

Talkad, Arun; Mathews, Maureen; Honings, Debra; Jahnel, Jan; Wang, D.

doi:10.1212/01.wnl.0000158683.20315.2a

Cited by 8 publications

(4 citation statements)

References 3 publications

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“…1,3 Whereas chronic treatment with VKA increases long-term risk of intracerebral hemorrhage 2-to 5-fold, 8 data on secondary hemorrhage following thrombolysis under effective OAC (INR, 2-3) in ischemic stroke are limited. In small case series, patients received thrombolysis after reversal of anticoagulation, 9,10 but the effectiveness and safety of this regimen is unclear.…”

mentioning

confidence: 99%

Rapid Reversal of Anticoagulation Prevents Excessive Secondary Hemorrhage After Thrombolysis in a Thromboembolic Model in Rats

Sun

Zhou

Ploen

et al. 2011

Stroke

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Background and Purpose-Thrombolysis is the only approved therapy for ischemic stroke, but secondary hemorrhage is a severe complication. Because oral anticoagulants are believed to increase the risk of hemorrhage, thrombolysis is usually contraindicated in patients on vitamin K antagonists. We studied whether thrombolysis in a thromboembolic middle cerebral artery occlusion model in rats pretreated with warfarin increases secondary hemorrhage, and whether substitution of coagulation factors before thrombolysis prevents hemorrhagic complications. Methods-Wistar rats were anticoagulated using warfarin in drinking water (0.4 mg/kg per 24 hours). Strength of anticoagulation was monitored using benchside international normalized ratio (INR) coagulometry. Two hours after middle cerebral artery occlusion, recombinant tissue-type plasminogen activator (9 mg/kg) was administered. Two of 5 groups of animals received prothrombin complex concentrate (PCC, 50 U/kg) 15 minutes before thrombolysis. Serial magnetic resonance imaging was performed 20 minutes, 2.5 hours, and 24 hours after middle cerebral artery occlusion. Secondary hemorrhage was quantified on T2* magnetic resonance images as previously established. Results-Severity of hypoperfusion on initial perfusion-weighted imaging -magnetic resonance did not differ among groups. Thrombolysis resulted in successful reperfusion in all groups. Anticoagulated animals had significantly more secondary hemorrhage and a higher mortality rate compared with nonanticoagulated animals. PCC rapidly reversed the increased international normalized ratio. Although PCC failed to prevent hemorrhage in the strongly anticoagulated, it reduced the incidence of severe hemorrhage in moderately anticoagulated rats (INR, 2-3) to the level of nonanticoagulated controls. Conclusions-Preceding

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mentioning

confidence: 99%

Rapid Reversal of Anticoagulation Prevents Excessive Secondary Hemorrhage After Thrombolysis in a Thromboembolic Model in Rats

Sun

Zhou

Ploen

et al. 2011

Stroke

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“…25 Another case report described correction of the INR in an elderly patient with rVIIA followed by rt-PA administration for a stroke. 26 Based on this review, we conclude that rVIIa appears to rapidly correct the INR; however, its clinical impact on bleeding in patients taking warfarin remains unclear. This conclusion is based on the observation that currently available evidence consists mainly of small (1-16 patients), nonrandomized, retrospective, case series and case reports without adequate controls.…”

Section: Evidence-based Guidelines __________________________________mentioning

confidence: 90%

What Is the Evidence for the Off-label Use of Recombinant Factor VIIa (rFVIIa) in the Acute Reversal of Warfarin?

Rosovsky¹,

Crowther²

2008

Hematology

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A 47-year-old man presents with hypovolemic shock. He takes warfarin as a result of a mechanical mitral valve insertion 5 years prior, his INR at presentation is 8.4 and emergent CT reveals a very large retroperitoneal hematoma. Despite aggressive fluid and transfusion support he continues hypotensive, requiring ionotrope support. You are asked if he should receive recombinant factor VIIa.To examine current best evidence of the effect of recombinant factor VIIa (rFVIIa) on the reversal of warfarin-induced coagulopathy, we performed a comprehensive computerized literature search of the OVID database using the terms warfarin (MESH, no restrictions, 13764 hits), AND recombinant factor VIIa (MESH, including factor VII, factor VIIa, and recombinant FVIIa, 5928 hits), AND reversal (MESH, no restrictions, 39639 hits) OR correction (MESH, no restrictions, 72783 hits) between 1950 and week 2 May 2008. This strategy provided 22 hits. There were 4 additional studies gleaned from the reference list of 2 of the articles. 1-4 Twelve papers were excluded: 7 were review articles, 5-11 3 described effects of clotting factor concentrates or vitamin K and not rFVIIa, 12-14 1 compared the in vitro antifibrinolytic activity of prothrombin complex concentrates to rFVIIa, 15 and 1 was a case report of rFVIIa in a phenindione overdose. 16 Five case series, 5 case reports, 1 retrospective casecontrol, 1 retrospective chart review, and 1 database review were retrieved. There was also 1 study involving healthy volunteers that included a dose finding study followed by a randomized controlled trial.The randomized double-blind placebo controlled trial was a pharmacokinetic-pharmacodynamic study of 28 healthy volunteers given acenocoumarol followed by rFVIIa (doses ranging from 5 to 320 μg/kg). The dose finding aspect of the study revealed that a single dose of 5 μg/kg normalized the INR for 12 hours and doses >120 μg/kg normalized the INR for 24 hours. The placebo had no effect on the INR. 2

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“…While several agents, such as vitamin K, protamine, fresh frozen plasma (FFP), and prothrombin complexes (PCCs), are used to reverse anticoagulation, we selected rFVIIa for our patient because its safe and rapid action for this purpose has been documented in several case studies 9–13. In addition, animal studies indicate that rFVIIa may be effective in reversing the anticoagulant effect of LMWH 14,15.…”

Section: Discussionmentioning

confidence: 99%

Successful management of bleeding with recombinant factor VIIa (NovoSeven®) in a patient with Burkitt lymphoma and thrombosis of the left femoral and left common iliac veins

Čulić

Kuljiš

Armanda

et al. 2006

Pediatric Blood & Cancer

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We present the case of an 18-year-old female with Burkitt lymphoma involving the intra-abdominal and inguinal lymph nodes. The tumor had invaded the left femoral and common iliac veins causing secondary thrombosis and vessel occlusion. Chemotherapy and anticoagulant treatment resulted in mild thrombocytopenia and a prolonged prothrombin time, respectively, which exacerbated postoperative bleeding following surgical removal of a deep inguinal necrosis. After 6 days, bleeding combined with epistaxis was considered to be life threatening and anticoagulant reversal with recombinant factor VIIa was successfully performed. The patient has since achieved complete remission and subsequent antithrombotic therapy has resolved the vascular occlusion.

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Reversal of warfarin-induced anticoagulation with factor VIIa prior to rt-PA in acute stroke

Cited by 8 publications

References 3 publications

Rapid Reversal of Anticoagulation Prevents Excessive Secondary Hemorrhage After Thrombolysis in a Thromboembolic Model in Rats

Rapid Reversal of Anticoagulation Prevents Excessive Secondary Hemorrhage After Thrombolysis in a Thromboembolic Model in Rats

What Is the Evidence for the Off-label Use of Recombinant Factor VIIa (rFVIIa) in the Acute Reversal of Warfarin?

Successful management of bleeding with recombinant factor VIIa (NovoSeven®) in a patient with Burkitt lymphoma and thrombosis of the left femoral and left common iliac veins

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