Summary
Cathepsin G (Cath G), a serine-protease found in neutrophils, has been reported to
have effects that could either facilitate or impede coagulation. Thrombin generation
(CAT method) was chosen to study its overall effect on the process, at a plasma concentration
(240 nM) observed after neutrophil activation. Coagulation was triggered by tissue
factor in the presence of platelets or phospholipid vesicles. To help identify potential
targets of Cath G, plasma depleted of clotting factors or of inhibitors was used.
Cath G induced a puzzling combination of two diverging effects of varying intensities
depending on the phospholipid surface provided: accelerating the process under the
three conditions (shortened clotting time by up to 30%), and impeding the process
during the same thrombin generation time-course since thrombin peak and ETP (total
thrombin potential) were decreased, up to 45% and 12%, respectively, suggestive of
deficient prothrombinase. This is consistent with Cath G working on at least two targets
in the coagulation cascade. Our data indicate that coagulation acceleration can be
attributed neither to platelet activation and nor to activation of a clotting factor.
When TFPI (tissue factor pathway inhibitor) was absent, no effect on lag time was
observed and the anticoagulant activity of TFPI was decreased in the presence of Cath
G. Consistent with the literature and the hypothesis of deficient prothrombinase,
experiments using Russel’s Viper Venom indicate that the anticoagulant effect can
be attributed to a deleterious effect on factor V. The clinical relevance of these
findings deserves to be studied.
Keywords
Cathepsin G - thrombin generation - TFPI - factor V - neutrophils
