title: International normalized ratio increase before warfarin-associated hemorrhage: brief and subtle.
abstract: OBJECTIVE
  To determine the relationship between serial international normalized ratios (INRs) in patients who have been undergoing long-term anticoagulation and the onset of warfarin-associated bleeding complications.
  
  
  METHODS
  The study cohort consisted of 2391 patients treated in the Anticoagulation Service at Brigham and Women's Hospital, Boston, Mass, from April 1999 through July 2003. For each patient with a bleeding event, we selected 2 controls who were matched for age, sex, indication for warfarin therapy, and duration of enrollment in our Anticoagulation Service.
  
  
  RESULTS
  Warfarin-related hemorrhage occurred in 32 patients (1.3%). The mean +/- SD INRs at the time of the bleeding event or matched patient's event date (5.9 +/- 5.9 vs 2.3 +/- 0.7; P<.001) and the mean+/-SD last INRs before the bleeding event or matched patient's event date (3.0 +/- 1.2 vs 2.1 +/- 0.8; P<.001) were higher in the patients than in the controls. The last INRs before the bleeding event were obtained an average of 11.6 +/- 17.8 (mean +/- SD) days before the event in the patients and 18.3 +/- 28.0 (mean +/- SD) days before the matched date in the controls (P = .22). The mean second-to-last INRs were similar in both groups (2.8 +/- 2.1 vs 2.3 +/- 0.8; P = .11). When the INRs were plotted in relation to the time before the onset of bleeding, a marked increase in the patients' INRs was observed shortly before the bleeding began.
  
  
  CONCLUSIONS
  Serial INRs are poor predictors of hemorrhagic events. There appears to be only a brief warning period during which a slightly elevated INR predicts an imminent bleeding event.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Kucher
authors.forename: Shannon
authors.initials: S
authors.lastname: Connolly
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Beckman
authors.forename: Lay Har
authors.initials: LH
authors.lastname: Cheng
authors.forename: Kanella V
authors.initials: KV
authors.lastname: Tsilimingras
authors.forename: John
authors.initials: J
authors.lastname: Fanikos
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin