Detection of procoagulant imbalance Modified endogenous thrombin potential with results expressed as ratio of values with-to-without thrombomodulin

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 ETP-TM 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.