The uniqueness of this case is amplified by the post hoc identification of four thrombophilia-associated genetic polymorphisms—Factor V Leiden, PAI-1 4G/5G, MTHFR C677T, and ACE I/D DD—which together may have exerted a synergistic prothrombotic influence, potentially contributing to the development of life-threatening thrombotic events, including massive pulmonary embolism and peripheral arterial occlusion. The gene discussed is SERPINE1; the disease is pulmonary embolism.