title: Genetically engineered serine protease inhibitor for hemostasis after cardiac operations.
abstract: BACKGROUND
  The serine protease inhibitor aprotinin has been widely reported for its beneficial action in limiting blood loss after cardiopulmonary bypass (CPB). A potent human serine protease inhibitor known as protease nexin II or amyloid precursor protein has been recently isolated. A recombinant protein known as recombinant Kunitz protease inhibitor (rKPI; Scios Nova, Mountain View, CA) with sequence homology to the protease nexin II-amyloid precursor protein molecule has been manufactured.
  
  
  METHODS
  Recombinant Kunitz protease inhibitor was assessed in an ovine model of CPB as a hemostatic agent after CPB. Sheep (n = 22) underwent CPB for 90 minutes. Two thoracic drains were sited and drain losses collected for a period of 3 hours after CPB. Wounds were subjectively assessed before closure for "dryness" using a visual analogue scale. Sheep were randomized to control (n = 8), aprotinin (n = 8), and rKPI (n = 6) groups.
  
  
  RESULTS
  Control animals had a drain loss of 409.4 +/- 39.4 mL/3 h, compared with 131.3 +/- 20.3 mL/3 h for the aprotinin group and 163.7 +/- 34.3 mL/3 h for the rKPI group (p = 0.16). Hemoglobin loss was 11.6 +/- 3.6, 6.02 +/- 2.1, and 4.6 +/- 1.2 g/3 h for the control, rKPI, and aprotinin groups respectively (p = 0.25). The subjective analysis of the wounds at the end of CPB found aprotinin (1.25 +/- 0.16; p < 0.05) and rKPI (1.17 +/- 0.17; p < 0.05) animals to score significantly lower than control animals (2.63 +/- 0.42).
  
  
  CONCLUSIONS
  On the basis of these in vivo findings, genetic modification may yield a more efficacious serine protease inhibitor with the inherent advantages of using a human-based protein.
authors.affiliation: Cardiothoracic Unit, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
authors.forename: S K
authors.initials: SK
authors.lastname: Ohri
authors.forename: R
authors.initials: R
authors.lastname: Paratt
authors.forename: J M
authors.initials: JM
authors.lastname: Becket
authors.forename: J
authors.initials: J
authors.lastname: Brannan
authors.forename: B J
authors.initials: BJ
authors.lastname: Hunt
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D004353:Drug Evaluation, Preclinical; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D011446:Prospective Studies; D011897:Random Allocation; D011994:Recombinant Proteins / Q000627:therapeutic use; D017385:Sequence Homology; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D012756:Sheep; D013997:Time Factors
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; C098973:recombinant Kunitz protease inhibitor; D007611:Aprotinin