Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

Adrian R Parry-Jones, Mario Di Napoli, Joshua N Goldstein, Floris H B M Schreuder, Sami Tetri, Turgut Tatlisumak, Bernard Yan, Koen M van Nieuwenhuizen, Nelly Dequatre-Ponchelle, Matthew Lee-Archer, Solveig Horstmann, Duncan Wilson, Fulvio Pomero, Luca Masotti, Christine Lerpiniere, Daniel Agustin Godoy, Abigail S Cohen, Rik Houben, Rustam Al-Shahi Salman, Paolo PennatiLuigi Fenoglio, David Werring, Roland Veltkamp, Edith Wood, Helen M Dewey, Charlotte Cordonnier, Catharina J M Klijn, Fabrizio Meligeni, Stephen M Davis, Juha Huhtakangas, Julie Staals, Jonathan Rosand, Atte Meretoja

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)54-62
Number of pages9
JournalAnnals of Neurology
Issue number1
Publication statusPublished - Jul 2015

Keywords / Materials (for Non-textual outputs)

  • Aged
  • Aged, 80 and over
  • Anticoagulants
  • Antifibrinolytic Agents
  • Blood Coagulation Factors
  • Cerebral Hemorrhage
  • Female
  • Humans
  • Male
  • Plasma
  • Proportional Hazards Models
  • Registries
  • Retrospective Studies
  • Treatment Outcome
  • Vitamin K


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