greater than 12 min were regarded as grossly abnormal those nails were cauterized to prevent excessive blood loss an anesthetized normal dog was administered doses of tissue factor protein representing 50 and 250 u kg of tissue factor protein on relipidation in the chromogenic assay the cbt in this animal was approximately 3 min prior to any infusion fig3 factor v levels were normal 30 min after each infusion table 6 the prothrombin and partial thromboplastin times were unchanged at the end of the experiment and the cbts were also within the normal range thus the infusion of tissue factor protein was well tolerated in normal dogs and no evidence of disseminated intravascular coagulation was found a hemophilic dog with a prolonged cbt characteristic of hemophilia a was administered 50 u kg of tissue factor protein the cbt was normalized 30 min after this infusion fig3 this correction was not associated with an alteration in factor v levels nor was the prothrombin time lengthened table 6 the procoagulant effect was not maintained 90 min after the infusion as the cbt effect was again abnormal at this time point a dose response relationship was established by infusion of 250 tissue factor protein u kg at this dose the cbt of the hemophilic dog was normalized at 30 and 90 min fig3 this increased dosage was however associated with a decrease in factor v levels and a slight lengthening of the prothrombin time table 6 as a consequence experiments were repeated using a dose of 100 tissue factor protein u kg in order to obtain the maximum duration of efficacy while ensuring that other coagulation factor levels were unaffected thus a hemophilic.