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Protein S deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Protein S deficiency

Protein S deficiency is a genetic disorder that increases the risk of developing blood clots, such as deep vein thrombosis (DVT) and pulmonary embolism (PE).

Overview

Protein S deficiency is a disorder that increases the risk of developing blood clots. People with this condition are at risk of developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the arms or legs. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening clot called a pulmonary embolism (PE). Both DVTs and PEs are a type of venous thromboembolism, a general term for blood clots that form in a vein.

Factors such as age, surgery, immobility, or pregnancy can increase the risk of clotting in people with protein S deficiency. In addition, people who have protein S deficiency and another inherited blood clotting disorder may have a higher risk of developing blood clots. Venous thromboembolism occurs in approximately fifty to sixty percent of people with protein S deficiency.

In rare cases, individuals have a severe form of protein S deficiency with signs and symptoms that develop soon after birth. Affected infants typically develop a life-threatening blood clotting disorder called purpura fulminans. This condition is characterized by the formation of blood clots within small blood vessels throughout the body, which disrupt normal blood flow and can lead to the death of tissues (necrosis). Widespread blood clotting uses up all available blood clotting proteins, leading to bleeding in various parts of the body, often appearing as large, purple skin lesions.

Frequency

Protein S deficiency is estimated to occur in approximately 1 in 500 individuals. The severe form of protein S deficiency that develops in infancy is rare, although its exact prevalence is unknown.

Causes

Protein S deficiency can be caused by variants (also called mutations) in the PROS1 gene. This gene provides instructions for making protein S, which is found in the bloodstream and is important for the control of blood clotting. Protein S helps block the activity of (inactivate) certain proteins that promote the formation of blood clots.

  • Most variants that cause protein S deficiency change single DNA building blocks (base pairs) in the PROS1 gene, changing the amount of functional protein S.
  • Individuals with protein S deficiency may not have enough functional protein S to inactivate clotting proteins, which increases the risk of developing blood clots.
  • Some cases of protein S deficiency are acquired, meaning they are not caused by gene variants. Causes of acquired protein S deficiency include vitamin K deficiency, liver disease, and kidney disorders.

Gene Associated with Protein S Deficiency

  • PROS1

Inheritance

Protein S deficiency is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of clotting.

In rare cases, a person has a variant in both copies of the PROS1 gene. This is typical of individuals with the severe form of protein S deficiency that develops in infancy. This form is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Acquired protein S deficiency is not inherited.

Frequently Asked Questions

Protein S levels are measured with a functional assay (protein S activity) and sometimes an antigen assay (total protein S). Blood should be drawn while you are not acutely ill, not on anticoagulants that affect the test (e.g., warfarin), and after fasting for at least 8 hours. Repeat testing on a separate day is recommended because levels can fluctuate with infection, pregnancy, or oral contraceptive use.
Because protein S deficiency is inherited in an autosomal dominant pattern, first‑degree relatives have a 50 % chance of carrying the mutation. Testing is advised if a family member has had a clot, if you have a known pathogenic variant, or if a clinician suspects a hereditary clotting disorder. Testing can be done with a simple blood draw; genetic counseling is helpful to interpret results.
The biggest triggers are prolonged immobility (long flights or bed rest), surgery, trauma, pregnancy, hormonal therapy (including oral contraceptives), and severe dehydration. To lower risk, stay mobile during long trips, use compression stockings, maintain adequate hydration, avoid estrogen‑containing birth control, and discuss prophylactic anticoagulation with your doctor before major surgery or during high‑risk periods such as pregnancy.
If you have had a first unprovoked DVT, most specialists recommend indefinite anticoagulation because the recurrence risk is high. If the clot was provoked by a temporary factor (e.g., surgery) and you have no other risk factors, a finite course of 3–6 months may be sufficient. Decisions are individualized; regular follow‑up labs and reassessment of bleeding risk guide whether therapy can be tapered or stopped.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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