Protein S is a vitamin K–dependent plasma glycoprotein that acts as an anticoagulant cofactor for activated protein C, promoting cleavage and inactivation of clotting factors Va and VIIIa to reduce thrombin formation. Only the free form is active; deficiency or dysfunction increases venous thrombosis risk. It also participates in apoptotic cell clearance and modulation of inflammation.

A protein S test is a blood test that measures the amount or activity of protein S, a natural anticoagulant. It helps evaluate inherited or acquired thrombophilia in people with unexplained or recurrent blood clots, family history of thrombosis, or recurrent pregnancy loss. Results guide diagnosis and treatment decisions; medication (especially warfarin) and acute illness can lower protein S, so timing and interpretation matter.

Low protein S reduces natural anticoagulation (it’s a cofactor for activated protein C), increasing risk of abnormal clots—especially deep vein thrombosis and pulmonary embolism—and less commonly cerebral or visceral venous thrombosis. It may be inherited or acquired (liver disease, vitamin K deficiency, some drugs, pregnancy). Management often includes anticoagulation and treating underlying causes; specialist evaluation is recommended.

Treatment focuses on preventing and treating blood clots. Acute venous thromboembolism is managed with heparin or low‑molecular‑weight heparin followed by oral anticoagulation (warfarin or direct oral anticoagulants). Long‑term or lifelong anticoagulation may be recommended for recurrent or high‑risk patients. Avoid estrogen‑containing contraceptives, provide thrombosis prophylaxis in surgery/pregnancy (LMWH), and offer family screening and specialist counseling.

Protein S deficiency is an inherited or acquired clotting disorder that raises the risk of venous thrombosis. It is not automatically classified as a disability; whether it counts depends on severity, complications (recurrent clots, pulmonary embolism), functional limitations, and local laws or benefits criteria. Individuals with significant, persistent impairment may qualify for accommodations or disability benefits—consult your clinician and local disability services for assessment.

Protein S is not a vitamin. It’s a vitamin K–dependent plasma glycoprotein made mainly in the liver that acts as a natural anticoagulant by serving as a cofactor for activated protein C. Proper vitamin K is needed for its function; inherited or acquired protein S deficiency raises the risk of venous thrombosis.