title: Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage.
abstract: OBJECTIVE
  Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K-dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA.
  
  
  METHODS
  Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion.
  
  
  RESULTS
  The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patient's hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications.
  
  
  CONCLUSIONS
  The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA. ravi.sarode@utsouthwestern.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Sarode
authors.forename: Karén
authors.initials: K
authors.lastname: Matevosyan
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhagat
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rutherford
authors.forename: Christopher
authors.initials: C
authors.lastname: Madden
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Beshay
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000506:poisoning*; D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000009:adverse effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D002985:Clinical Protocols; D004338:Drug Combinations; D015942:Factor VIIa / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006406:Hematoma / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D014812:Vitamin K / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000506:poisoning*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D004338:Drug Combinations; D011994:Recombinant Proteins; D014812:Vitamin K; C025667:prothrombin complex concentrates; D014859:Warfarin; C103587:recombinant FVIIa; D015942:Factor VIIa