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

BackgroundThe 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 <1pmol are used. ObjectivesTo determine whether blood collection tubes containing CTI influenced TGA parameters. MethodsThis 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 33gmL(-1) and no CTI. ResultsCTI 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. ConclusionsThis 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 1pmol L-1.