Management of High-Risk Pulmonary Thromboembolism Caused by Double Heterozygous PROS1/PROC Mutations Despite Normal Protein C Activity: A Case Report on ECMO Combined with Interventional Thrombectomy
Hereditary deficiencies of protein C (PC) and protein S (PS) are major risk factors for pulmonary thromboembolism (PTE) in Asian populations. While PROC and PROS1 mutations cause PC and PS deficiency respectively, the risk and mechanism of dual heterozygous mutations, especially with normal PC activity, remain unclear. We report a young male with high-risk PTE and obstructive shock, successfully managed by VA-ECMO-assisted interventional thrombectomy. Workup revealed severely reduced PS activity (28.3%) with normal PC activity (99.7%). Genetic testing identified heterozygous pathogenic mutations in PROS1 (c.1680T>A, p.Tyr560Ter) and PROC (c.577_579delAAG, p.Lys193del), inherited respectively from his asymptomatic parents. This suggests that severe PS deficiency can unmask the thrombogenic potential of a PROC mutation despite normal PC activity, leading to life-threatening thrombosis. The case underscores the importance of systematic thrombophilia screening in young high-risk PTE patients and demonstrates the value of an integrated, multidisciplinary approach centered on ECMO-bridged intervention.