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Blood Test Tracker

Protein S, Free Antigen

Measures the active, unbound form of protein S, a natural blood thinner. It is the test many labs use first to look for low protein S.

AI-verified against cited sources. Awaiting expert reviewAlso called Free PS, PS freeLOINC 27821-8

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The usual range for Free Protein S depends on sex. Choose female or male above to see where you stand.

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What it is

Protein S works with protein C to keep your blood from clotting too easily. About two-thirds of the protein S in your blood is attached to a carrier protein and is inactive. The rest is free, and only the free part does the job. This test measures the amount of free protein S with an antibody-based method, not with a clotting time. It is reported as a percent of normal, and the usual range is lower for women than for men.

Why it matters

A low free protein S level can raise the chance of blood clots in veins. Most low results come from something other than an inherited problem, such as pregnancy, birth control pills, warfarin, low vitamin K, liver disease, a recent clot or a serious illness. A lasting inherited shortage is uncommon. Testing is usually reserved for a clot with no clear cause, a clot at a young age or in an unusual place, or a strong family history. Results are most reliable when you have recovered from any recent clot, are not pregnant and are not taking warfarin.

If it’s low

A low result can be real or temporary. Babies normally have lower levels. In adults, common reasons include pregnancy, hormone medicines, warfarin, low vitamin K, liver disease, a recent clot and serious illness. A lasting inherited shortage is less common, and it is confirmed by repeating the test when none of those apply. Even then, a low level raises the chance of a clot but does not mean you will have one.

Common causes

  • Pregnancy and the weeks after delivery
  • Birth control pills or hormone therapy that contain estrogen
  • Warfarin or other vitamin K blockers, or low vitamin K
  • Liver disease, or kidney disease with heavy protein loss
  • A recent blood clot, an infection, inflammation or another acute illness
  • Sickle cell disease
  • Inherited protein S deficiency (uncommon)

What can help

  • Ask when the best time to test is. Labs advise a gap of 2 to 4 weeks after warfarin and waiting until you have recovered from a clot. Never stop a blood thinner on your own.
  • Ask whether a total protein S antigen test or protein S activity test would help explain the result
  • If you are pregnant or take a medicine that contains estrogen, tell your clinician, because both lower protein S
  • If an inherited shortage is confirmed, ask whether relatives should be offered testing

If it’s high

A result above the range is not known to cause health problems. Your clinician can put it in context with your other results.

Common causes

  • Natural variation between people
  • Being compared with the wrong age or sex range

What can help

  • Usually nothing needs to be done
  • Ask your clinician whether the result fits with your other clotting tests

Usual ranges

What labs print as the reference range, by who was tested. Ranges differ a little between labs, so the range on your own report is the one your result is judged against.

The usual range depends on sex and age. Choose women or men to see the one that applies.

Children and teens 6 ranges

See Free Protein S by age and sex, with the U.S. survey numbers where they exist.

What can affect your result

  • Sex: published ranges are lower for women than for men
  • Age: babies and children have lower levels
  • Pregnancy, the weeks after delivery, and estrogen-containing medicines
  • Warfarin and vitamin K status
  • Liver and kidney disease, a recent clot, infection and acute illness
  • Warfarin and other vitamin K blockers lower protein S. ARUP says not to order the test within 2 to 4 weeks of warfarin. Never stop a blood thinner on your own to get tested.
  • Pregnancy and the weeks after delivery, estrogen-containing birth control or hormone therapy, liver disease, kidney disease with heavy protein loss, a recent clot, infection, inflammation and sickle cell disease all lower protein S.
  • This is an immunoassay, so it is less likely than a clot-based protein S test to be thrown off by factor V Leiden, a lupus anticoagulant or blood thinners.
  • Babies have lower levels, so age-specific ranges are needed.

An inherited level does not change over time. Levels linked to pregnancy, hormones, warfarin or illness move as the cause changes, over days to weeks.

When to talk to a clinician

A low free protein S result is not an emergency by itself, but ask the clinician who ordered it to review it with you. Call 911 or your local emergency number for possible signs of a clot: sudden chest pain or shortness of breath, a swollen, painful or warm leg, sudden weakness or numbness on one side, trouble speaking, or a sudden severe headache.

Questions you could ask

  • Which range does my lab use, and is it split by sex and age?
  • Is protein C being checked at the same time?
  • Does this result fit with my other clotting tests?
  • Is this a good time to test, given pregnancy, hormones, recent illness or a clot?
  • Should we repeat the test or add a total protein S antigen or activity test?
  • Does this result matter for my relatives?

Questions people ask

Why do men and women have different usual ranges?

Lab-published ranges for free protein S are lower for women than for men. Pregnancy and estrogen-containing medicines can lower protein S further, so tell your clinician if either applies to you.

How is this different from the protein S activity test?

This test counts the free, active protein S. The activity test measures how well protein S works using a clotting time, and factor V Leiden, a lupus anticoagulant or blood thinners can throw it off. Many labs use free antigen first and the activity test as a second step.

Can I be tested while on warfarin, pregnant or soon after a clot?

Those situations can all lower protein S, so the result may not show your usual level. ARUP says not to order the test within 2 to 4 weeks of warfarin, and UK guidance says to wait until 3 months of treatment for an acute clot. Your clinician decides the timing, and you should not stop a blood thinner on your own.

Show the science and sources

Units

  • 1 % = 1 %
  • 1 % = 1 IU/dL

Is a change real?

Free Protein S naturally varies about 4.2% from test to test in the same healthy person. Between two results from the same lab, a change of roughly 13% or more is unlikely to be day-to-day noise or lab variation (95% reference change value). Source: Systematic review and meta-analysis of within-subject and between-subject biological variation data of coagulation and fibrinolytic measurands (Hollestelle MJ et al.).

For clinicians and researchers

Free protein S antigen is measured by an immunoassay that excludes protein S bound to C4b-binding protein, either by removing the complex first (for example with polyethylene glycol) or by using an antibody against an epitope hidden in the bound form. ARUP (microlatex particle-mediated immunoassay) and Mayo (latex immunoassay) run it as an automated assay. Free protein S antigen correlates well with protein S activity, so many labs measure only free antigen. ARUP calls it the preferred test for protein S deficiency, and the BSH 2022 guideline lists free protein S antigen as the assay to use. An isolated low functional result with normal free antigen (type II) is rare and is easily produced by factor V Leiden, high factor VIII or a lupus anticoagulant in clot-based tests. Hereditary types are I (free, bound and total reduced), III (free reduced, total normal) and II (function reduced, antigen normal). Mayo's thrombophilia profile adds a total protein S antigen when free antigen is under 65% in men and women 50 and over, or under 50% in women and girls under 50. Heterozygous deficiency raises the risk of a first venous clot about 5–7-fold. Reference intervals vary by method and sex, for example ARUP 74–147% for men and 55–123% for women, and Indiana University Health 59–118%.

LOINC 27821-8 (primary), 4677-1. Specimen: plasma.

Sources

  1. Protein S Free, Antigen (test 0098894), ARUP Laboratories
  2. Thrombophilia Profile, Plasma and Whole Blood (test ID AATHR), Mayo Clinic Laboratories (Extended Catalog, via testcatalog.org)
  3. Thrombosis & Hemostasis Reference Ranges (updated 1/11/2021), Indiana University Health Pathology Laboratory (2021)
  4. Protein S Assays, Practical-Haemostasis.com
  5. Thrombophilia testing: A British Society for Haematology guideline, British Journal of Haematology (2022)
  6. Protein C and Protein S Tests, MedlinePlus, National Library of Medicine

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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