title: Overall haemostatic potential can be used for estimation of thrombin-activatable fibrinolysis inhibitor-dependent fibrinolysis in vivo and for possible follow-up of recombinant factor VIIa treatment in patients with inhibitors to factor VIII.
abstract: Thrombin generation induced by recombinant factor VIIa (rFVIIa) in patients with haemophilia and/or inhibitors to factor VIII/IX could enhance generation of thrombin-activatable fibrinolysis inhibitor (TAFI), a recently described link between coagulation and fibrinolysis. TAFI is unstable and it is not easy to measure its active form in vivo. Overall haemostatic potential (OHP) is a novel method for haemostasis estimation, based on determination of the fibrin aggregation curve in which tiny amounts of thrombin are used for activation of clotting. We measured OHP in six patients with inhibitors to factor VIII before injection of rFVIIa and 10 and 120 min thereafter. Overall fibrinolytic potential (OFP) and clot lysis time (CLT) analysed by this method could be used for indirect estimation of TAFI generation. We found no change in pro-TAFI and total TAFI antigen before and after treatment with rFVIIa. OHP was almost undetectable before treatment but increased into the range of normal pooled plasma 10 and 120 min after rFVIIa treatment, as did CLT. However, after addition of potato tuber carboxypeptidase inhibitor, a specific inhibitor of TAFI, the shortening of CLT was lower than that in NPP. OFP was increased in patient plasma both 10 and 120 min after treatment compared with NPP. There was a strong positive correlation between pro-TAFI concentration and shortening of CLT after PTCI addition and a negative correlation between pro-TAFI concentration and OFP 10 min after rFVIIa injection. Thus, rFVIIa normalizes OHP and CLT 10 min after injection. While this improvement slightly decreases, but still exists after 2 hours, it suggests efficacy in bleeding prevention using a protocol based on rFVIIa administration every 2 hours.
authors.affiliation: Coagulation Research, Department of Surgical Sciences, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. jovan.antovic@kirurgi.ki.se
authors.forename: J P
authors.initials: JP
authors.lastname: Antovic
authors.forename: A
authors.initials: A
authors.lastname: Antovic
authors.forename: S
authors.initials: S
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Tengborn
authors.forename: M
authors.initials: M
authors.lastname: Blombäck
mesh_terms: D025901:Carboxypeptidase B2 / Q000096:biosynthesis*; D005167:Factor VII / Q000627:therapeutic use*; D005169:Factor VIII / Q000037:antagonists & inhibitors; D015942:Factor VIIa; D005342:Fibrinolysis / Q000502:physiology*; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006487:Hemostasis; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; D025901:Carboxypeptidase B2; D015942:Factor VIIa