757: HIGH-DOSE FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE FOR WARFARIN-INDUCED INTRACEREBRAL HEMORRHAGE

INTRODUCTION: Warfarin-associated intracerebral hemorrhage (wICH) remains the most lethal form of iatrogenic stroke. Conventional therapy with fresh frozen plasma (FFP) and intravenous vitamin K takes up to 30 hrs to normalize the international normalized ratio (INR). Prothrombin complex concentrate (PCC) does not require cross-match and is fast acting. We hypothesized that PCC can rapidly reverse coagulopathy and reduce mortality in wICH. Methods: We identified 130 consecutive adult wICH patients over five years from a prospectively collected database. 33 patients were excluded for death or withdrawal of care within 48 hours of admission and 8 patients were excluded for antecedent head trauma, leaving 89 patients for analysis. Forty patients received FFP and vitamin K (conventional therapy) and 49 received PCC in addition to conventional therapy. We compared 6-month mortality, time to INR normalization, quantity of FFP transfused, and thromboembolic complication rates between the two groups. We used logistic regression to adjust for important confounders. Results: PCC-treated and conventional therapy patients had similar distributions of age, sex, co-morbidities, ICH location, initial blood pressure and INR. PCC-treated patients had a higher incidence of intraventicular hemorrhage (IVH) (67% vs 33%). PCC-treated patients required less FFP (mean 6.8 units vs 3.3 units, p<0.0001) and had faster time to INR normalization (mean 3.8 hrs vs 9.8 hrs, p<0.0001). Incidence of ICH expansion was low in both groups. There was no difference in the incidence of deep venous thrombosis and pulmonary embolism (p=0.236) or troponin elevation (p=0.573). There was no significant difference in 6-month mortality (p=0.437) after adjusting for age, ICH location, ICH volume, and presence of IVH. Conclusions: PCC use in wICH was associated with shorter time to INR normalization and reduced FFP transfusion but was not associated with 6-month mortality in this cohort. There was no difference in thromboembolic complication rates between PCC-treated and FFP and vitamin K treated patients. Prospective trials of PCC are necessary to determine if its use can improve morbidity and mortality in wICH and to identify potential subgroups of wICH patients who may benefit from PCC.

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Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1607993 ◽

2017 ◽

Vol 38 (06) ◽

pp. 726-736 ◽

Cited By ~ 5

Author(s):

Lanting Fuh ◽

Jonathan Sin ◽

Joshua Goldstein ◽

Bryan Hayes

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Prothrombin Complex Concentrate ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Quality Data ◽

Reversal Agent ◽

Intravenous Vitamin ◽

Time Of Presentation

AbstractIn patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non–vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

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Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage

Journal of Neurosurgery ◽

10.3171/2011.11.jns11836 ◽

2012 ◽

Vol 116 (3) ◽

pp. 491-497 ◽

Cited By ~ 54

Author(s):

Ravi Sarode ◽

Karén Matevosyan ◽

Ramesh Bhagat ◽

Cynthia Rutherford ◽

Christopher Madden ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Prothrombin Complex Concentrate ◽

Factor Viia ◽

Standard Of Care ◽

Factor Vii ◽

Plasma Therapy ◽

The Us ◽

Thrombotic Complications ◽

Warfarin Reversal

Object Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K–dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA. Methods Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion. Results The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patient's hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications. Conclusions The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.

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