title: Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case-control study.
abstract: BACKGROUND
  Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.
  
  
  METHODS
  We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.
  
  
  RESULTS
  Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).
  
  
  CONCLUSIONS
  Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Schou1@partners.org
authors.forename: Chou Sherry
authors.initials: CS
authors.lastname: H-Y
authors.forename: Cai
authors.initials: C
authors.lastname: Xuemei
authors.forename: Konigsberg Rachael
authors.initials: KR
authors.lastname: G
authors.forename: Bresette Linda
authors.initials: BL
authors.lastname: M
authors.forename: Henderson Galen
authors.initials: HG
authors.lastname: V
authors.forename: Sorond Farzaneh
authors.initials: SF
authors.lastname: A
authors.forename: Feske Steven
authors.initials: FS
authors.lastname: K
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015942:Factor VIIa / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D011994:Recombinant Proteins; D014859:Warfarin; C103587:recombinant FVIIa; D015942:Factor VIIa