In vivo studies of activated porcine factor VIII. 1996

J D Littlewood, and S A Bevan, and G Kemball-Cook, and T W Barrowcliffe
Animal Health Trust, Newmarket, Suffolk, UK.

The haemostatic effectiveness of activated FVIII was compared to that of non-activated FVIII in a cross-over study in a canine model of haemophilia. Activation of FVIII in porcine concentrate was achieved by the addition of 3 x 10(-5) IU thrombin per ml of concentrate, which gave consistent increases in 1-stage FVIII activity of 13- to 14-fold and slow decay. The haemostatic effect was monitored by measurements of the cuticle bleeding time 10 and 45 min after infusion and there were no consistent differences between the activated and non-activated concentrates. One-stage factor VIII assays on plasmas 5 min after infusion showed identical mean values for activated and non-activated concentrates, indicating that most of the higher activity observed in vitro had disappeared rapidly from the circulation. These results suggest that controlled activation of FVIII by thrombin, which increases its activity in 1-stage assays, is unlikely to be of therapeutic benefit. For therapeutic concentrates which may contain small amounts of activated FVIII, the 1-stage assay may be an unreliable guide to their therapeutic effect.

UI MeSH Term Description Entries
D008297 Male Males
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D015944 Factor VIIIa Activated form of factor VIII. The B-domain of factor VIII is proteolytically cleaved by thrombin to form factor VIIIa. Factor VIIIa exists as a non-covalent dimer in a metal-linked (probably calcium) complex and functions as a cofactor in the enzymatic activation of factor X by factor IXa. Factor VIIIa is similar in structure and generation to factor Va. Coagulation Factor VIIIa,Factor VIII, Activated,Factor VIII, Thrombin-Activated,Blood Coagulation Factor VIII, Activated,Factor 8A,Factor Eight A,Factor VIIIa Heavy Chain, 200 kDa Isoform,Factor VIIIa Heavy Chain, 92 kDa Isoform,Factor VIIIa Light Chain,Activated Factor VIII,Factor VIII, Thrombin Activated,Factor VIIIa, Coagulation,Thrombin-Activated Factor VIII
D018592 Cross-Over Studies Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed) Cross-Over Design,Cross-Over Trials,Crossover Design,Crossover Studies,Crossover Trials,Cross Over Design,Cross Over Studies,Cross Over Trials,Cross-Over Designs,Cross-Over Study,Crossover Designs,Crossover Study,Design, Cross-Over,Design, Crossover,Designs, Cross-Over,Designs, Crossover,Studies, Cross-Over,Studies, Crossover,Study, Cross-Over,Study, Crossover,Trial, Cross-Over,Trial, Crossover,Trials, Cross-Over,Trials, Crossover

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