Failure of corn trypsin inhibitor to affect the thrombin generation assay in plasma from severe hemophiliacs

J Thromb Haemost. 2014 Sep;12(9):1558-61. doi: 10.1111/jth.12659. Epub 2014 Aug 7.

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.

Objectives: 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) .

Keywords: corn trypsin inhibitor; hemophilia; inhibitors; patient monitoring; thrombin.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Coagulation / drug effects
  • Blood Coagulation Tests
  • Blood Preservation / methods*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Factor VIII / antagonists & inhibitors
  • Hemophilia A / blood*
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Plant Proteins / chemistry*
  • Prospective Studies
  • Specimen Handling
  • Thrombin / chemistry*
  • Treatment Outcome
  • Young Adult

Substances

  • Plant Proteins
  • trypsin inhibitor, Zea mays
  • Factor VIII
  • Thrombin