title: Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage.
abstract: OBJECTIVE
  Anticoagulation-related intracerebral hemorrhage (ICH) is often fatal, and rapid reversal of anticoagulation is the most appealing strategy currently available for treatment. We sought to determine whether particular emergency department (ED) interventions are effective in reversing coagulopathy and improving outcome.
  
  
  METHODS
  Consecutive patients with warfarin-related ICH presenting to an urban tertiary care hospital from 1998 to 2004 were prospectively captured in a database. ED records were retrospectively reviewed for dose and timing of fresh-frozen plasma (FFP) and vitamin K, as well as serial coagulation measures. After excluding patients with incomplete ED records, do-not-resuscitate orders established in the ED, initial international normalized ratio (INR) < or =1.4, and for whom no repeat INR was performed, 69 patients were available for analysis. The primary outcome was a documented INR < or =1.4 within 24 hours of ED presentation.
  
  
  RESULTS
  Patients whose INR was successfully reversed within 24 hours had a shorter median time from diagnosis to first dose of FFP (90 minutes versus 210 minutes; P=0.02). In multivariable analysis, shorter time to vitamin K, as well as FFP, predicted INR correction. Every 30 minutes of delay in the first dose of FFP was associated with a 20% decreased odds of INR reversal within 24 hours (odds ratio, 0.8; 95% CI, 0.63 to 0.99). Dosing of FFP and vitamin K had no effect. No ED intervention was associated with improved clinical outcome.
  
  
  CONCLUSIONS
  Time to treatment is the most important determinant of 24-hour anticoagulation reversal. Although additional study is required to determine the clinical benefit of rapid reversal of anticoagulation, minimizing delays in FFP administration is a prudent first step in emergency management of warfarin-related ICH.
authors.affiliation: Department of Emergency Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA. jgoldstein@partners.org
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Goldstein
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Thomas
authors.forename: Virginia
authors.initials: V
authors.lastname: Frontiero
authors.forename: Annelise
authors.initials: A
authors.lastname: Joseph
authors.forename: Chana
authors.initials: C
authors.lastname: Engel
authors.forename: Ryan
authors.initials: R
authors.lastname: Snider
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001803:Blood Transfusion / Q000379:methods*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000628:therapy*; D004635:Emergency Medicine / Q000379:methods; D005260:Female; D006761:Hospitals; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010949:Plasma / Q000378:metabolism; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000627:therapeutic use; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin