title: Clot lysis phenotype and response to recombinant factor VIIa in plasma of haemophilia A inhibitor patients.
abstract: Recombinant activated factor VII (rFVIIa) is a haemostatic agent that is used for the treatment of haemophilia A patients with inhibitors. However, clinical response to rFVIIa is variable and unpredictable with currently available assays. We investigated the anti-fibrinolytic effects of rFVIIa in relation to thrombin generation (TG) and other haemostatic parameters in haemophilia A patients with inhibitors. After addition of rFVIIa to plasma, the clot-lysis assay, TF-dependent TG, TF-independent TG and parameters involved in coagulation, anticoagulation and fibrinolysis were assessed. The clot-lysis test distinguished two groups of patients: a group with a normal and a group with impaired anti-fibrinolytic response to rFVIIa. Our results showed a dose-dependent increase in TF-dependent TG and TF-independent TG in all individuals. There was a significant difference in TF-independent TG parameters between the normal and impaired response groups. In addition, there was a difference between the normal and impaired response group in prothrombin time, which could be explained by significantly higher levels of coagulation factors in the normal response group, and soluble thrombomodulin. In conclusion, we observed different in vitro responses following rFVIIa addition in plasma of patients with haemophilia A and inhibitors, which could be partially attributed to levels of procoagulant proteins and soluble thrombomodulin.
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Kamran
authors.initials: K
authors.lastname: Bakhtiari
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: Maria E
authors.initials: ME
authors.lastname: Mancuso
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyak
authors.forename: Roger E G
authors.initials: RE
authors.lastname: Schutgens
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D002648:Child; D005169:Factor VIII / Q000037:antagonists & inhibitors; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D063285:Fibrin Clot Lysis Time; D005342:Fibrinolysis / Q000187:drug effects; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000378:metabolism; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D011994:Recombinant Proteins; D005169:Factor VIII; D005337:Fibrin; D015942:Factor VIIa; D013917:Thrombin
keywords: anti-fibrinolytic response; clot-lysis test; factor VIII inhibitors; haemophilia A; recombinant factor VIIa