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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. A possible solution is proposed by use of global 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 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.