title: The effect of recombinant and plasma-derived prothrombin on prothrombin time in human plasma.
abstract: BACKGROUND
  When investigating coagulation assays to measure the effect of infused prothrombin (FII) in in vivo coagulopathy models, we found that addition of FII, plasma-derived human FII (pd-hFII) or recombinant human FII (r-hFII), to normal plasma resulted in a concentration-dependent increase in prothrombin time (PT) initiated with Innovin(®) .
  
  
  METHODS
  The effect on PT by addition to plasma of either pd-hFII or r-hFII, using different commercial PT reagents, was studied both by turbidimetry and viscometry.
  
  
  RESULTS
  Addition of FII to plasma resulted in increased PT when initiated with Innovin(®) : PT increased with 20% by doubling the concentration. The prolongation of PT became more pronounced with 2-6000 times diluted Innovin(®) . However, by adjustment of the final free Ca(2+) concentration in the assay with diluted Innovin(®) from 8.3 to 1.3 mmol/L, no FII-dependent increase in PT was found. In contrast, no prolongation of PT was found with other commercial PT reagents. A KM = 3 nmol/L was obtained with pd-hFII, respectively, r-hFII with FII-depleted plasma using Thromborel(®) to initiate PT.
  
  
  CONCLUSIONS
  At normal plasma concentration of FII, addition of FII should not have an effect on PT. The prolonged PT with Innovin(®) , but not with other PT reagents, at supranormal FII concentration is an artefact.
authors.affiliation: Department of Bioscience, CVMD iMED, AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: K M
authors.initials: KM
authors.lastname: Hansson
authors.forename: J
authors.initials: J
authors.lastname: Björkqvist
authors.forename: J
authors.initials: J
authors.lastname: Deinum
mesh_terms: D001798:Blood Proteins; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D011516:Prothrombin / Q000008:administration & dosage / Q000494:pharmacology*; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology; D013925:Thromboplastin / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; C082196:Innovin; D011994:Recombinant Proteins; D011516:Prothrombin; D013925:Thromboplastin; D002118:Calcium
keywords: Prothrombin time; calcium; plasma coagulation; prothrombin; tissue factor