Clinical characteristics, genes identification and follow-up study of a patient with central venous thrombosis from a protein S deficiency pedigree.

OBJECTIVE: To explore the clinical and prognostic features of CVT caused by PROS1 gene mutations and to provide clinical experience for new oral anticoagulants, such as rivaroxaban, in the treatment of CVT with a high risk of thrombosis. PATIENTS AND METHODS: The CVT patient's clinical symptoms were described, and the brain imaging and blood coagulation tests were performed to confirm the diagnosis of CVT. The patient's family members were recruited to receive blood coagulation tests and ultrasonic examination of lower limb vessels. Genetic analysis on the pedigree was carried out to identify the responsible gene for PS deficiency. We followed-up with this patient for 24 months to evaluate the clinical outcomes, laboratory results and imaging performances of CVT. RESULTS: The patient presented with typical CVT symptoms, including headache and epilepsy. Brain CT showed hemorrhage in the bilateral frontal lobe and left occipital lobe, while MRV demonstrated that thrombus had occurred. It was reviewed that the patient and his mother had a history of bilateral leg deep vein thrombosis. Gene tests revealed that the patient and two family members carried a heterozygous mutation of PROS1 (c.751_752delAT, p.M251Vfs*17). During 24 months of follow-up study, the patient was treated with rivaroxaban continuously and recovered well, supported by an mRS score that remained below 2. Blood coagulation tests were within normal limits, and MRV revealed partial recanalization of the cerebral venous sinus. CONCLUSIONS: The frame shift mutation in the PROS1 gene (c.751_752delAT) may greatly affect the function of protein S and lead to a severe phenotype of CVT. Rivaroxaban showed a satisfying therapeutic effect in this CVT patient with hereditary thrombophilia.