title: Laboratory assessment of warfarin reversal with global coagulation tests versus international normalized ratio in patients with intracranial bleeding.
abstract: We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890  nmol/min and 123  nmol and increased significantly to 1943  nmol/min (P < 0.01) and 301  nmol (P < 0.01) 30  min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.
authors.affiliation: aDepartment of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida bCoagulation Advancement Laboratory, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia, USA cFaculty of Pharmacy, Department of Clinical Pharmacy, Cairo University, Cairo, Egypt dNeuroscience Intensive Care Unit, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Voils
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Martin
authors.forename: Bassem M
authors.initials: BM
authors.lastname: Mohammed
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bayrlee
authors.forename: Donald F
authors.initials: DF
authors.lastname: Brophy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D013916:Thrombelastography; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014859:Warfarin