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In this review, we discuss the role of inherited abnormalities of blood coagulation in <jats:styled-content style=\"fixed-case\">VTE<\/jats:styled-content> pathogenesis. In addition, we also consider recent emerging data suggesting other molecular and cellular determinants may also contribute. Specifically, we describe the role played by the inflamed endothelium, and the dysregulated responses to inflammatory stimuli that create a platform for pathological clot formation. We review the accumulating evidence that blood cells, contact pathway factors and protein disulphide isomerases all play key roles in <jats:styled-content style=\"fixed-case\">VTE<\/jats:styled-content> development. Finally, we discuss new insights into the role of metabolites arising from commensal gut bacteria and their potential role in facilitating <jats:styled-content style=\"fixed-case\">VTE<\/jats:styled-content>. 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