title: Failure of corn trypsin inhibitor to affect the thrombin generation assay in plasma from severe hemophiliacs.
abstract: BACKGROUND
  The thrombin generation assay (TGA) is an important global coagulation assay; however, it suffers from the lack of preanalytical standardization. The addition of corn trypsin inhibitor (CTI) to blood collection tubes before TGA has been previously advocated to block the contact activation pathway. Emerging data, however, suggest that CTI may only be necessary when minimal tissue factor (TF) concentrations < 1 pmol are used.
  
  
  OBJECTIVE
  To determine whether blood collection tubes containing CTI influenced TGA parameters.
  
  
  METHODS
  This cross-sectional, observational study performed the TGA using TF 1 pmol L(-1) in 15 healthy volunteers, 14 severely factor VIII (FVIII)-deficient patients, and 15 severely FVIII-deficient patients with documented FVIII inhibitors. TGA was conducted using blood tubes that contained CTI 33 μg mL(-1) and no CTI.
  
  
  RESULTS
  CTI markedly reduced peak thrombin (P = 0.002) and endogenous thrombin potential (P < 0.001) in the healthy volunteers but had no significant effect on TGA parameters in severely FVIII-deficient patients or those with inhibitors.
  
  
  CONCLUSIONS
  This lack of effect raises additional questions regarding the need for CTI as a preanalytical addition to blood collection tubes during TGA in severe hemophiliacs, particularly when activating samples with TF 1 pmol L(-1) .
authors.affiliation: Coagulation Advancement Laboratory, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA; Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: B M
authors.initials: BM
authors.lastname: Mohammed
authors.forename: E J
authors.initials: EJ
authors.lastname: Martin
authors.forename: V
authors.initials: V
authors.lastname: Salinas
authors.forename: R
authors.initials: R
authors.lastname: Carmona
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.forename: D F
authors.initials: DF
authors.lastname: Brophy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001793:Blood Preservation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005169:Factor VIII / Q000037:antagonists & inhibitors; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D010940:Plant Proteins / Q000737:chemistry*; D011446:Prospective Studies; D013048:Specimen Handling; D013917:Thrombin / Q000737:chemistry*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010940:Plant Proteins; C052160:trypsin inhibitor, Zea mays; D005169:Factor VIII; D013917:Thrombin
keywords: corn trypsin inhibitor; hemophilia; inhibitors; patient monitoring; thrombin