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Blood Test Tracker

Protein S Activity

Measures how well protein S works. Protein S is a natural blood thinner that helps protein C keep your blood from clotting too easily.

AI-verified against cited sources. Awaiting expert reviewAlso called PS ActivityLOINC 27822-6

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What it is

Protein S is a protein made in the liver and other tissues that needs vitamin K to work. With protein C, it switches off two of the proteins that make blood clot. About two-thirds of protein S in your blood is attached to a carrier protein and does not work. The rest is free and active. This clot-based test measures how much activity the free form has. It is reported as a percent of normal, and the usual range is lower for women than for men.

Why it matters

A low 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. Many labs prefer the free protein S antigen test as the first check because it is less easily thrown off by other clotting problems, and use this activity test as a second step. 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.

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 lab effect from factor V Leiden, a high factor VIII level or a lupus anticoagulant can also push this clot-based result down. 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 or another acute illness
  • A clot-based test misread because of factor V Leiden, a high factor VIII level or a lupus anticoagulant
  • 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 free protein S antigen test would help confirm 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. It can be a lab effect, for example from heparin or a direct oral anticoagulant in the sample.

Common causes

  • Natural variation between people
  • Heparin, direct thrombin inhibitors or factor Xa inhibitors in the sample (a lab effect)

What can help

  • Usually nothing needs to be done
  • Ask your clinician whether a medicine you take could affect the lab method used

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 15 ranges

See Protein S Activity 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
  • Heparin and newer blood thinners (they can raise the result)
  • Factor V Leiden, a high factor VIII level or a lupus anticoagulant (they can lower the result)
  • Warfarin and other vitamin K blockers lower protein S. ARUP advises waiting about 2 weeks off warfarin for an accurate functional result, and its ordering notes say not to order within 2 to 4 weeks of warfarin. Never stop a blood thinner on your own to get tested.
  • Heparin, direct thrombin inhibitors and factor Xa inhibitors can make a functional protein S result read falsely high.
  • Factor V Leiden and other causes of activated protein C resistance, a high factor VIII level, and a lupus anticoagulant can make the clot-based result read falsely low.
  • 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 and other acute illness all lower protein S.
  • 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 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 method did my lab use, and does it match the range printed on my report?
  • Is protein C being checked at the same time?
  • Could a medicine I take have affected this result?
  • Is this a good time to test, given pregnancy, hormones, recent illness or a clot?
  • Should we repeat the test or add a free protein S antigen test?
  • Does this result matter for my relatives?

Questions people ask

Why are the usual ranges lower for women?

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

Is the activity test or the free antigen test better?

Many labs, including ARUP and Mayo, treat the free protein S antigen test as the preferred first test and use the activity test as a second step. The activity test is easier to throw off with factor V Leiden, a lupus anticoagulant or blood thinners. Your clinician chooses what fits your situation.

Can pregnancy or birth control cause a low result?

Yes. Protein S falls in pregnancy and in the weeks after delivery, and some people on estrogen-containing birth control have lower levels. A low result in those situations is often temporary. Your clinician may suggest repeating the test later.

Show the science and sources

Units

  • 1 % = 1 %
  • 1 % = 1 IU/dL

Is a change real?

Protein S Activity naturally varies about 7.3% from test to test in the same healthy person. Between two results from the same lab, a change of roughly 23% 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

Protein S is a vitamin K–dependent glycoprotein (half-life about 42 hours) made in the liver, endothelium and megakaryocytes. It is the cofactor for activated protein C in inactivating factors Va and VIIIa and also has activated-protein-C–independent anticoagulant activity. About 65% circulates bound to C4b-binding protein and is inactive. Only the free form is active. Functional assays are aPTT-based or PT-based clotting assays run on protein S–deficient plasma with activated protein C or a protein C activator, and they measure free protein S activity. They are sensitive to lupus anticoagulants, activated protein C resistance (factor V Leiden, high factor VIII), direct thrombin inhibitors and other anticoagulants. ARUP names free protein S antigen as its preferred test and lists this functional assay as acceptable, and Mayo uses this assay as a second-order test after free protein S antigen. The BSH 2022 guideline lists free protein S antigen as the assay for protein S. Hereditary types are I (free, bound and total reduced), II (normal antigen, low function) and III (free reduced, total normal). Type II is rare, and many apparent type II cases turn out to be factor V Leiden. Heterozygous deficiency raises the risk of a first venous clot about 5–7-fold. Reference intervals differ by lab and sex, for example ARUP 66–143% for men and 57–131% for women, and Mayo 65–150% for men, 50–150% for women under 50 and 65–150% for women 50 and over.

LOINC 27822-6 (primary), 31102-7, 5892-5. Specimen: plasma.

Sources

  1. Protein S, Functional (test 0030114), ARUP Laboratories
  2. Protein S Activity, Plasma (test ID SFX), Mayo Clinic Laboratories (Extended Catalog, via testcatalog.org)
  3. Protein S Assays, Practical-Haemostasis.com
  4. Thrombosis & Hemostasis Reference Ranges (updated 1/11/2021), Indiana University Health Pathology Laboratory (2021)
  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
  7. Protein S Free, Antigen (test 0098894), ARUP Laboratories

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

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