Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage
Open accessAbstract
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.
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In VKA-treated patients with intracranial haemorrhage and INR ≥ 1.3, the combination of plasma and prothrombin complex concentrates is associated with the lowest case fatality.
“Registry data suggest that the combination of plasma and prothrombin complex concentrates is associated with the lowest case fatality following intracranial haemorrhage on VKA treatment with an INR ≥ 1.3.506”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [506]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
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- Authors
- Parry‐Jones, A. R., Di Napoli, M., Goldstein, J. N., Schreuder, F. H. B. M., Tetri, S., Tatlisumak, T., Yan, B., van Nieuwenhuizen, K. M., Dequatre‐Ponchelle, N., Lee‐Archer, M., Horstmann, S., Wilson, D., Pomero, F., Masotti, L., Lerpiniere, C., Godoy, D. A., Cohen, A. S., Houben, R., Al‐Shahi Salman, R., Pennati, P., Fenoglio, L., Werring, D., Veltkamp, R., Wood, E., Dewey, H. M., Cordonnier, C., Klijn, C. J. M., Meligeni, F., Davis, S. M., Huhtakangas, J., Staals, J., Rosand, J., & Meretoja, A.
- Affiliations
- National Health Service (GB)
- Neurological Service, San Camillo de' Lellis General Hospital Rieti Italy
- Massachusetts General Hospital (US)
- Maastricht University Medical Centre (NL)
- Oulu University Hospital (FI)
- Helsinki University Hospital (FI)
- The Royal Melbourne Hospital (AU)
- Department of Neurology and Neurosurgery Rudolf Magnus Brain Center, University Medical Center Utrecht Utrecht the Netherlands
- Centre Hospitalier Universitaire de Lille (FR)
- Austin Hospital (AU)
- Heidelberg University (DE)
- University College London (GB)
- Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT)
- Internal Medicine, Cecina Hospital Cecina Italy
- University of Edinburgh (GB)
- Neurointensive Care Unit, Pasteur Sanatorium Catamarca Argentina
- Centre for Clinical Brain Sciences, University of Edinburgh Edinburgh United Kingdom
- University Medical Center Utrecht (NL)
- Department of Medical Emergency San Camillo de' Lellis General Hospital Rieti Italy
- Corresponding author
- Meretoja, Atte
- ORCID
- Parry‐Jones, Adrian R.
- Goldstein, Joshua N.
- Schreuder, Floris H. B. M.
- Tetri, Sami
- Tatlisumak, Turgut
- Yan, Bernard
- Wilson, Duncan
- Pomero, Fulvio
- Masotti, Luca
- Pennati, Paolo
- Fenoglio, Luigi
- Werring, David
- Veltkamp, Roland
- Dewey, Helen M.
- Cordonnier, Charlotte
- Klijn, Catharina J. M.
- Davis, Stephen M.
- Huhtakangas, Juha
- Staals, Julie
- Rosand, Jonathan
- Meretoja, Atte
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-05-14
- Volume
- 78
- Issue
- 1
- Pages
- 54-62
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4654243
- OpenAlex
- W1842572227
- Cited by
- 90
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 15 · 2016: 18 · 2015: 7
- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- Research Explorer (The University of Manchester) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- University of Manchester
- Academy of Medical Sciences
- Dowager Countess Eleanor Peel Trust
- British Heart Foundation
- Stroke Association
- Medical Research Council
- Hartstichting (2012T077)
- Netherlands Organisation for Health Research and Development (015008048)
- National Institutes of Health (R01 NS059727)
- Suomen Akatemia
- National Health and Medical Research Council
- Finnish Brain Foundation
- Finnish Medical Foundation
- Helsinki University Central Hospital
- Italian National Health Service
- Natalie Kate Moss Trust
- Salford Royal NHS Foundation Trust
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- intracerebral hemorrhage, vitamin K antagonists, anticoagulant reversal, fresh frozen plasma, prothrombin complex concentrate, case fatality, 30-day mortality, bleeding complications, international normalized ratio, stroke registry, pooled analysis, combination therapy, bleeding risk stratification
- MeSH terms
- Aged, Aged, 80 and over, Anticoagulants, Antifibrinolytic Agents, Blood Coagulation Factors, Cerebral Hemorrhage, Female, Humans, Male, Plasma, Registries, Retrospective Studies, Vitamin K, Proportional Hazards Models, Treatment Outcome
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