Summary
Each individual possesses his/her own endogenous-thrombin-potential (ETP) (i. e. the
ability to generate thrombin) which depends on the relative strength of the pro- and
anticoagulant drivers operating in plasma. This ability depends in turn on the clinical
conditions in which the balance between the two drivers is variably affected. One
of the major determinants of this balance is the factor (F)VIII-protein C(PC) axis
and its effect can be conveniently explored by the thrombin generation procedures
with results expressed as ETP ratio with/without thrombomodulin (TM) (ETP-TM ratio).
Furthermore, owing to the many feedback mechanisms mediated by thrombin (e. g. activation
of PC, FXI, FV, FVIII, platelets etc.) it is also possible that any perturbation of
the balance between pro- and anticoagulants that may occur in plasma even outside
the FVIII-PC axis could result in an increased ETPTM ratio and therefore may suggest
a procoagulant imbalance. Indeed, other non-coagulation moieties (e. g. microparticles,
neutrophil extracellular traps, pro-inflammatory cytokines and others) circulating
in blood of patients with various clinical conditions may also contribute to the procoagulant
imbalance even when FVIII and/or PC are apparently normal. It can be postulated that
dual ETP measurements performed in the presence and absence of TM with results expressed
as their ratio may be the candidate procedure to detect subtle procoagulant imbalance
in many clinical conditions characterised by an increased risk of thromboembolism.
This article aimed at reviewing the clinical conditions in which evidence for the
value of the ETP-TM ratio has been provided.
Keywords Hypercoagulability - thrombosis - protein C/S pathway - factor VIII