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Protein C and Protein S Tests
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Lab Tests

Protein C and Protein S Tests

Protein C and protein S tests measure the levels and function of these proteins in your blood to determine if you are at an increased risk for developing blood clots.

What are protein C and protein S tests?

These tests use a blood sample to measure the quantity and function of protein C and protein S. While often performed together, they are separate tests. Normally, these proteins work together to prevent excessive blood clotting.

A deficiency in either protein can cause your blood to clot too much, even without injury, leading to:

  • Deep vein thrombosis (DVT): Blood clots in the veins of your legs or pelvis.
  • Pulmonary embolism: A life-threatening condition where clots travel to your lungs.

Most deficiencies are acquired, meaning they result from other conditions or medicines, such as infections, liver or kidney disease, vitamin K deficiency, cancer, chemotherapy, pregnancy, or the use of birth control pills or warfarin. In rare cases, deficiencies are inherited due to a genetic change.

What are they used for?

Providers use these tests to:

  • Identify the cause of an unexplained blood clot and assess future risk.
  • Check for and determine the type of protein C or S deficiency.
  • Monitor protein levels to see if a deficiency has improved or worsened.

Functional tests measure how well the proteins work, while quantity tests determine if your body is making enough of them. Deficiencies are generally categorized as either a low quantity of the protein or the presence of dysfunctional proteins.

Why do I need protein C and protein S tests?

Testing may be necessary if you have experienced:

  • A blood clot before age 50 without a known cause.
  • A blood clot in an unusual location, such as the kidneys, liver, or brain.
  • Multiple blood clots.
  • A need to monitor treatment for a known clotting disorder.

Testing may also be indicated if you have a family history of inherited deficiency, if you are a newborn with a clotting disorder, or if you have conditions (like liver or kidney disease) that can cause acquired deficiencies.

What happens during protein C and protein S testing?

A health care professional will take a blood sample from a vein in your arm using a small needle. The procedure typically takes less than five minutes.

Will I need to do anything to prepare for the test?

If you are being tested following a blood clot, you must wait until you have fully recovered for accurate results. Your provider may also ask you to stop taking blood thinners for several days before the test; however, never stop prescription medication without consulting your provider first.

Are there any risks to the test?

There is very little risk. You may experience slight pain or bruising at the needle site, which usually goes away quickly.

What do the results mean?

Higher than normal levels are not known to cause health problems. Lower than normal levels, or proteins that do not function well, indicate an increased risk of blood clots.

If a deficiency is inherited, you may require genetic testing, and the increased risk for clots will be lifelong. If acquired, the deficiency may be temporary or long-lasting. Treatment may include blood thinners (anticoagulants), treating the underlying cause, or avoiding triggers like smoking and birth control pills.

Is there anything else I need to know?

If you have a diagnosed deficiency, inform your provider during high-risk situations such as surgery, pregnancy, trauma, or periods of immobility (like long trips). Your provider can offer strategies to reduce clot risk, such as movement during travel, preventative medication, or education on recognizing warning signs like sudden swelling, leg pain, chest pain, or shortness of breath.

Frequently Asked Questions

If a first‑degree relative has a confirmed protein C or S deficiency, cascade testing is advised. Genetic sequencing of the PROC (protein C) and PROS1 (protein S) genes can identify pathogenic variants. Testing is typically performed after age 12 or earlier if the child has a personal clotting event. Counseling about the implications of a positive result is essential before testing.
Testing is best done at least 2–3 weeks after the acute event and after you have been off anticoagulants (warfarin, heparin, DOACs) for a minimum of 1 week, because these drugs and the acute‑phase response can falsely lower levels. If you are on long‑term anticoagulation, a repeat test after a medication “wash‑out” period (often 2 weeks for warfarin) is recommended, or you can have a functional assay that is less affected by therapy.
Estrogen‑containing contraceptives can reduce protein S antigen and activity by 20‑30 %. Most women see levels normalize within 4–6 weeks after discontinuation, but you should repeat testing after that interval to confirm. If levels remain low, further evaluation for an inherited deficiency is warranted.
Warfarin interferes with the vitamin K–dependent activation of protein C and protein S, lowering activity results but usually not antigen levels. Therefore, the antigen (quantity) assay is more reliable while you are on warfarin. After stopping warfarin for at least 1 week, repeat the activity test to assess true functional deficiency.
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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