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Protein S deficiency is a rare blood-clotting disorder in which the body has reduced levels or activity of protein S, a natural anticoagulant that helps regulate blood clot formation. Protein S works with protein C to prevent excessive clotting and maintain healthy blood circulation. When protein S is insufficient, the blood may become more likely to form unwanted clots.

The condition can be inherited through genetic changes or develop because of other factors, including pregnancy, liver disease, vitamin K deficiency, certain medications, and some medical conditions. Many people with protein S deficiency may have no symptoms until a clot develops. Common complications include deep vein thrombosis (DVT), which usually affects the legs, and pulmonary embolism (PE), when a clot travels to the lungs.

Diagnosis generally involves blood tests that measure protein S levels and activity. Genetic testing may sometimes help identify an inherited form. Doctors may consider personal and family history when evaluating the risk of thrombosis.

Treatment depends on an individual's clotting history and risk factors. Anticoagulant medicines may be prescribed to prevent or treat blood clots. People with protein S deficiency should discuss surgery, pregnancy, prolonged travel, and other clotting risks with their healthcare provider.