Etiology of Thrombotic Disorders Genetic defects that increase the propensity for venous thromboembolism include Factor V Leiden mutation, which causes resistance to activated protein C (APC) Prothrombin 20210 gene mutation Deficiency of protein C Deficiency of protein S Deficiency of protein Z Antithrombin deficiency Acquired defects also predispose to venous and arterial thrombosis (see table Acquired Causes of Thromboembolism).