- Hereditary protein S deficiency prevalence is <1% in individuals with VTE.
- Deficiency is autosomal dominant, with most cases due to PROS1 mutation.
- Function
- Protein S regulates coagulation negatively.
- Circulates in free and bound forms (to C4b-binding protein); only the free form is active.
- Acts as a cofactor for protein C, which inactivates factors Va and VIIIa.
- Diagnosis
- Diagnosis is challenging; free protein S levels (measured by immunoassay) are the best screening test.
- Diagnosis requires repeat testing and consideration of family history.
- Misdiagnosis can occur during acute VTE, pregnancy, certain illnesses, or anticoagulant use (especially VKAs).Rare 0.3-2%
- Management
- Acute VTE management is similar to the general population: anticoagulation for 3–6 months.
- Indefinite anticoagulation may be indicated for unprovoked VTE, strong family history, or documented deficiency.