Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk

Thrombosis is a deadly malfunctioning of the hemostatic system occurring in numerous conditions and states, from surgery and pregnancy to cancer, sepsis and infarction. Despite availability of antithrombotic agents and vast clinical experience justifying their use, thrombosis is still responsible for a lion's share of mortality and morbidity in the modern world. One of the key reasons behind this is notorious insensitivity of traditional coagulation assays to hypercoagulation and their inability to evaluate thrombotic risks; specific molecular markers are more successful but suffer from numerous disadvantages. A possible solution is proposed by use of global, or integral, assays that aim to mimic and reflect the major physiological aspects of hemostasis process in vitro. Here we review the existing evidence regarding the ability of both established and novel global assays (thrombin generation, thrombelastography, thrombodynamics, flow perfusion chambers) to evaluate thrombotic risk in specific disorders. The biochemical nature of this risk and its detectability by analysis of blood state in principle are also discussed. We conclude that existing global assays have a potential to be an important tool of hypercoagulation diagnostics. However, their lack of standardization currently impedes their application: different assays and different modifications of each assay vary in their sensitivity and specificity for each specific pathology. In addition, it remains to be seen how their sensitivity to hypercoagulation (even when they can reliably detect groups with different risk of thrombosis) can be used for clinical decisions: the risk difference between such groups is statistically significant, but not large.