title: Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: University of Manchester, Manchester Academic Health Sciences Centre, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.|Greater Manchester Neurosciences Centre, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors: Adrian R
authors: AR
authors: Parry-Jones
authors: Neurological Service, San Camillo de' Lellis General Hospital, Rieti, Italy.|Neurological Section, Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention (SMDN), Sulmona, Italy.
authors: Mario
authors: M
authors: Di Napoli
authors: Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA.
authors: Joshua N
authors: JN
authors: Goldstein
authors: Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Floris H B M
authors: FH
authors: Schreuder
authors: Department of Neurology, Oulu University Hospital, Oulu, Finland.
authors: Sami
authors: S
authors: Tetri
authors: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Turgut
authors: T
authors: Tatlisumak
authors: Department of Neurology, Royal Melbourne Hospital, Parkville, Australia.
authors: Bernard
authors: B
authors: Yan
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Koen M
authors: KM
authors: van Nieuwenhuizen
authors: Department of Neurology, University of Lille Nord de France (UDSL), Lille University Hospital Center, Lille, France.
authors: Nelly
authors: N
authors: Dequatre-Ponchelle
authors: Department of Neurology, Austin Hospital, Heidelberg, Australia.
authors: Matthew
authors: M
authors: Lee-Archer
authors: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors: Solveig
authors: S
authors: Horstmann
authors: University College London, London, United Kingdom.
authors: Duncan
authors: D
authors: Wilson
authors: Department of Internal Medicine, Santa Croce e Carle Hospital, Cuneo, Italy.
authors: Fulvio
authors: F
authors: Pomero
authors: Internal Medicine, Cecina Hospital, Cecina, Italy.
authors: Luca
authors: L
authors: Masotti
authors: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Christine
authors: C
authors: Lerpiniere
authors: Neurointensive Care Unit, Pasteur Sanatorium, Catamarca, Argentina.|Intensive Care Unit, San Juan Bautista Hospital, Catamarca, Argentina.
authors: Daniel Agustin
authors: DA
authors: Godoy
authors: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors: Abigail S
authors: AS
authors: Cohen
authors: Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Rik
authors: R
authors: Houben
authors: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Rustam
authors: R
authors: Al-Shahi Salman
authors: Internal Medicine, Cecina Hospital, Cecina, Italy.
authors: Paolo
authors: P
authors: Pennati
authors: Department of Internal Medicine, Santa Croce e Carle Hospital, Cuneo, Italy.
authors: Luigi
authors: L
authors: Fenoglio
authors: University College London, London, United Kingdom.
authors: David
authors: D
authors: Werring
authors: Department of Neurology, University of Heidelberg, Heidelberg, Germany.|Department of Medicine, Imperial College London, London, United Kingdom.
authors: Roland
authors: R
authors: Veltkamp
authors: Greater Manchester Neurosciences Centre, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors: Edith
authors: E
authors: Wood
authors: Department of Neurology, Austin Hospital, Heidelberg, Australia.
authors: Helen M
authors: HM
authors: Dewey
authors: Department of Neurology, University of Lille Nord de France (UDSL), Lille University Hospital Center, Lille, France.
authors: Charlotte
authors: C
authors: Cordonnier
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Catharina J M
authors: CJ
authors: Klijn
authors: Department of Medical Emergency, San Camillo de' Lellis General Hospital, Rieti, Italy.
authors: Fabrizio
authors: F
authors: Meligeni
authors: Department of Neurology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medicine and Florey Institute, University of Melbourne, Melbourne, Australia.
authors: Stephen M
authors: SM
authors: Davis
authors: Department of Neurology, Oulu University Hospital, Oulu, Finland.
authors: Juha
authors: J
authors: Huhtakangas
authors: Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Julie
authors: J
authors: Staals
authors: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors: Jonathan
authors: J
authors: Rosand
authors: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.|Department of Neurology, Royal Melbourne Hospital, Parkville, Australia.|Department of Medicine and Florey Institute, University of Melbourne, Melbourne, Australia.
authors: Atte
authors: A
authors: Meretoja
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D010949:Plasma; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D001779:Blood Coagulation Factors; D014812:Vitamin K; C025667:prothrombin complex concentrates