Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different...

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Published in:	Annals of neurology Vol. 78; no. 1; pp. 54 - 62
Main Authors:	Parry-Jones, Adrian R., Di Napoli, Mario, Goldstein, Joshua N., Schreuder, Floris H. B. M., Tetri, Sami, Tatlisumak, Turgut, Yan, Bernard, van Nieuwenhuizen, Koen M., Dequatre-Ponchelle, Nelly, Lee-Archer, Matthew, Horstmann, Solveig, Wilson, Duncan, Pomero, Fulvio, Masotti, Luca, Lerpiniere, Christine, Godoy, Daniel Agustin, Cohen, Abigail S., Houben, Rik, Al-Shahi Salman, Rustam, Pennati, Paolo, Fenoglio, Luigi, Werring, David, Veltkamp, Roland, Wood, Edith, Dewey, Helen M., Cordonnier, Charlotte, Klijn, Catharina J. M., Meligeni, Fabrizio, Davis, Stephen M., Huhtakangas, Juha, Staals, Julie, Rosand, Jonathan, Meretoja, Atte
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-07-2015 Wiley Subscription Services, Inc John Wiley and Sons Inc
Subjects:	Aged Aged, 80 and over Anticoagulants - adverse effects Antifibrinolytic Agents - therapeutic use Blood Coagulation Factors - therapeutic use Cerebral Hemorrhage - chemically induced Cerebral Hemorrhage - mortality Cerebral Hemorrhage - therapy Confidence intervals Fatalities Female Humans Male Plasma Proportional Hazards Models Registries Retrospective Studies Stroke Treatment Outcome Vitamin K - antagonists & inhibitors Vitamin K - therapeutic use
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Summary:	Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies. Methods We pooled individual ICH patient data from 16 stroke registries in 9 countries (n = 10 282), of whom 1,797 (17%) were on VKA. After excluding 250 patients with international normalized ratio < 1.3 and/or missing data required for analysis, we compared all‐cause 30‐day case fatality using Cox regression. Results We included 1,547 patients treated with FFP (n = 377, 24%), PCC (n = 585, 38%), both (n = 131, 9%), or neither (n = 454, 29%). The crude case fatality and adjusted hazard ratio (HR) were highest with no reversal (61.7%, HR = 2.540, 95% confidence interval [CI] = 1.784–3.616, p < 0.001), followed by FFP alone (45.6%, HR = 1.344, 95% CI = 0.934–1.934, p = 0.112), then PCC alone (37.3%, HR = 1.445, 95% CI = 1.014–2.058, p = 0.041), compared to reversal with both FFP and PCC (27.8%, reference). Outcomes with PCC versus FFP were similar (HR = 1.075, 95% CI = 0.874–1.323, p = 0.492); 4‐factor PCC (n = 441) was associated with higher case fatality compared to 3‐factor PCC (n = 144, HR = 1.441, 95% CI = 1.041–1.995, p = 0.027). Interpretation The combination of FFP and PCC might be associated with the lowest case fatality in reversal of VKA‐ICH, and FFP may be equivalent to PCC. Randomized controlled trials with functional outcomes are needed to establish the most effective treatment. Ann Neurol 2015;78:54–62
Bibliography:	Netherlands Organization for Health Research and Development - No. 015008048 ArticleID:ANA24416 Dutch Heart Foundation - No. 2012T077 ark:/67375/WNG-KNTM695N-1 istex:0B0B1A180E591C3E24F462863D943ECDBF0F0F7D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0364-5134 1531-8249
DOI:	10.1002/ana.24416