title: Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.
abstract: During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII.
  
  
  
  We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation.
  
  
  
  We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data.
  
  
  
  In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20).
  
  
  
  This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation.
authors.affiliation: Stellaris Pharmaceuticals ApS, Copenhagen, Denmark. Electronic address: birgit_lilienfeldt@hotmail.com.
authors.forename: Birgit T B G
authors.initials: BTBG
authors.lastname: Schjoldager
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Emmeli
authors.initials: E
authors.lastname: Mikkelsen
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Malene R
authors.initials: MR
authors.lastname: Lykke
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Præst
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Hvas
authors.affiliation: Gentofte, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Heslet
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Secher
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jannie D
authors.initials: JD
authors.lastname: Salvig
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Uldbjerg
mesh_terms: D000287:Administration, Topical; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical; D002585:Cesarean Section / Q000009:adverse effects / Q000379:methods*; D015942:Factor VIIa / Q000008:administration & dosage*; D005260:Female; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000098:blood supply / Q000187:drug effects; D010923:Placenta Previa / Q000188:drug therapy / Q000601:surgery*; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D006473:Postpartum Hemorrhage / Q000517:prevention & control; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: factor VIIa; hemostatic agents; maternal mortality; placenta previa; postpartum hemorrhage; topical treatment