Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. OBJECTIVES: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. METHODS: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. RESULTS: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. CONCLUSIONS: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.