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

Objective

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 PAI-1 and MTHFR gene mutations.

Methods

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 in situ hybridization). The iGenKB database was queried to determine the patient's and her close relatives' genetic risk scores and risk intervals.

Results

The patient was diagnosed with hereditary thrombophilia caused by PAI-1 4G/4G homozygous mutation combined with MTHFR heterozygous mutation, with multiple close relatives in the family having mutations in the PAI-1 gene and MTHFR 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.

Conclusions

The combination of a homozygous PAI-1 4G/4G mutation and a heterozygous MTHFR 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.