title: The combination of recombinant factor VIIa and fibrinogen correct clotting ex vivo in patient samples obtained following cardiopulmonary bypass surgery.
abstract: Cardiac surgery involving cardio pulmonary bypass (CPB) may be associated with development of a coagulopathy that increases risk of bleeding. In the present ex vivo study we investigated the influence of fibrinogen and rFVIIa, alone or in combination, on whole blood coagulation thromboelastometry using pre- and postoperative blood samples from 18 consecutive adult patients undergoing CPB surgery. Dynamic thromboelastometric clotting profiles were recorded using citrated whole blood activated with trace amounts of tissue factor (Innovin, final dilution 1:17000). Blood samples were collected before surgery (control) and postoperative samples were obtained following in vivo neutralization of heparin with protamine sulphate. All blood samples were treated with heparinase to ensure neutralization of possible residual heparin effect. The post-operative blood samples were spiked with buffer, rFVIIa (2 microg/mL), fibrinogen (1 mg/mL), or the combination of rFVIIa and fibrinogen. Despite neutralization of heparin, CPB surgery left a measurable coagulopathy that was thromboelastometrically characterized by prolonged onset of clotting, reduced maximum velocity of clot formation (MaxVel), and decreased maximum clot firmness (MCF). Ex vivo spiking of the postoperative samples with rFVIIa shortened the clotting time. Fibrinogen also shortened the clotting time and, in addition, improved the MaxVel, and MCF. Finally, adding the combination of rFVIIa and fibrinogen to the postoperative samples corrected all thromboelastometric parameters to the preoperative range. In conclusion, the correction of whole blood clotting abnormalities that occurs with rFVIIa and/or fibrinogen suggests that future clinical trials on treatment of bleeding during CPB surgery should study the haemostatic effect of fibrinogen or possibly the combination of rFVIIa and fibrinogen.
authors.affiliation: Center for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Benny
authors.initials: B
authors.lastname: Sørensen
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Asvaldsdottir
authors.forename: Brynja R
authors.initials: BR
authors.lastname: Gudmundsdottir
authors.forename: Pall T
authors.initials: PT
authors.lastname: Onundarson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000379:methods*; D015942:Factor VIIa / Q000008:administration & dosage*; D005340:Fibrinogen / Q000008:administration & dosage* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry; D019763:Heparin Lyase / Q000737:chemistry; D006801:Humans; D008875:Middle Aged; D011479:Protamines / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D011479:Protamines; D011994:Recombinant Proteins; D005340:Fibrinogen; D006493:Heparin; C103587:recombinant FVIIa; D015942:Factor VIIa; D019763:Heparin Lyase