title: Hematologic effects of recombinant factor VIIa combined with hemoglobin-based oxygen carrier-201 for prehospital resuscitation of swine with severe uncontrolled hemorrhage due to liver injury.
abstract: The combination of traumatic injury, hemorrhage, and fluid resuscitation results in consumption and dilution of coagulation factors, adversely impacting hematology outcome in trauma patients. The hemostatic effects of escalating doses of recombinant factor VIIa added to hemoglobin-based oxygen carrier-201 were assessed as prehospital fluid resuscitation in swine with severe uncontrolled hemorrhage. Swine underwent liver injury causing severe uncontrolled hemorrhage and shock. During a 4-h prehospital phase, either hypotensive or tachycardic, or both, animals were resuscitated with hemoglobin-based oxygen carrier-201 without (0x) or with escalating doses of recombinant factor VIIa [90 microg/kg (1x), 180 microg/kg (2x), or 360 microg/kg (4x)]. The animals received one initial full dose of 10 ml/kg at 15 min and up to four doses of 5 ml/kg thereafter. From 4 to 72 h (hospital phase), animals received either transfusions or isotonic saline or both as needed. Hematology profile (complete blood count), thromboelastography, in-vitro bleeding (platelet function analyzer), and coagulation (prothrombin time) were measured and the results were compared using mixed statistical models. In all groups, dilutional coagulopathy was evidenced by reduced hematocrit, platelets, and thromboelastography-maximum amplitude, and increased platelet function analyzer closure time and thromboelastography-reaction time. During the prehospital phase, hemoglobin-based oxygen carrier-201 restored hemoglobin in all groups. Recombinant factor VIIa decreased prothrombin time in recombinant factor VIIa groups compared with the hemoglobin-based oxygen carrier-201 group (P < 0.01). Unexpectedly, increasing recombinant factor VIIa dosage tended to increase fluid requirement (P > 0.05). Compared with hemoglobin-based oxygen carrier, 1x recombinant factor VIIa tended to decrease blood loss, lactate and thromboelastography-reaction time at 24 h but the 4x group increased these parameters. Platelets and thromboelastography-maximum amplitude decreased (P < 0.01) with the 4x group. In swine with severe uncontrolled hemorrhage, prehospital resuscitation with escalating doses of recombinant factor VIIa in combination with hemoglobin-based oxygen carrier-201 did not change survival or hemostasis. However, there were trends toward possible benefits of low recombinant factor VIIa doses, whereas high recombinant factor VIIa doses adversely affected hemostasis.
authors.affiliation: Combat Casualty Care, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. francoise.arnaud@MED.NAVY.MIL
authors.forename: Françoise
authors.initials: F
authors.lastname: Arnaud
authors.forename: Michael
authors.initials: M
authors.lastname: Hammett
authors.forename: Nora
authors.initials: N
authors.lastname: Philbin
authors.forename: Anke
authors.initials: A
authors.lastname: Scultetus
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D001803:Blood Transfusion; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000494:pharmacology*; D005440:Fluid Therapy; D006403:Hematologic Tests; D006454:Hemoglobins / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008099:Liver / Q000293:injuries*; D010976:Platelet Count; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy*; D013552:Swine; D013556:Swine, Miniature; D013916:Thrombelastography
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D011994:Recombinant Proteins; C096798:HBOC 201; C103587:recombinant FVIIa; D015942:Factor VIIa