[Pedigree analysis of hereditary thrombophilia caused by a pure mutation in the <i>PAI-1</i> gene combined with a heterozygous mutation in the <i>MTHFR</i> gene].

<b>Objective:</b> To improve the clinical capacity for diagnosis and treatment of inherited thrombophilia through the analysis of the diagnostic and therapeutic process of recurrent thrombosis caused by combined <i>PAI-1</i> and <i>MTHFR</i> gene mutations. <b>Methods:</b> We report a case of a 42-year-old female patient admitted with cough, expectoration, fever, and left lower limb pain. After suboptimal efficacy with standard-dose low-molecular-weight heparin (LMWH) and rivaroxaban, comprehensive thrombophilia genetic testing was performed. Six thrombophilia-associated genes were analyzed using a multi-channel fluorescent quantitative analyzer via the minisequencing method (modified <i>in situ</i> hybridization). The iGenKB database was queried to determine the patient's and her close relatives' genetic risk scores and risk intervals. <b>Results:</b> The patient was diagnosed with hereditary thrombophilia caused by <i>PAI-1 4G/4G</i> homozygous mutation combined with <i>MTHFR</i> heterozygous mutation, with multiple close relatives in the family having mutations in the <i>PAI-1</i> gene and <i>MTHFR</i> gene. Following adjustment of the anticoagulation regimen to rivaroxaban and implementation of individualized dosing guided by anti-Xa activity (rivaroxaban) monitoring, the patient's condition improved significantly. <b>Conclusions:</b> The combination of a homozygous <i>PAI-1 4G/4G</i> mutation and a heterozygous <i>MTHFR</i> mutation represents a rare inherited thrombophilia genotype. Genetic screening in younger patients presenting with unexplained thrombotic events or experiencing recurrent thrombosis despite standardized anticoagulant therapy. Additionally, this case highlights the necessity for individualized rivaroxaban dosing regimens based on drug activity monitoring.