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Protein C and Protein S

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Also known as: Protein C Activity; Protein C Level; Protein S Activity; Protein S Level
Formal name: Protein C, Functional or Antigen; Protein S, Functional or Antigen (Free or Total)

At a Glance

Why Get Tested?

To help evaluate inappropriate blood clot formation (thrombotic episode or thromboembolism); to determine whether you may have a protein C or protein S deficiency

When to Get Tested?

When you have had an unexplained blood clot; when your newborn has a severe clotting disorder; sometimes when a close relative has an inherited protein C or protein S deficiency

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

You must wait at least 10 days after a thrombotic episode and be off oral warfarin (Coumadin®) anticoagulant therapy for 2 weeks before having this test done. (See also Common Questions #1.)

The Test Sample

What is being tested?

Protein C and protein S are two proteins in the blood that help regulate blood clot formation. Two separate tests for these proteins are often performed together as part of the investigation of a possible excessive clotting disorder. The tests measure the amount of each protein and evaluate whether they are performing their proper functions.

Normally, when a body tissue or blood vessel wall is injured, a process called hemostasis begins to form a plug at the injury site to help stop the bleeding. Small cell fragments called platelets adhere to and aggregate at the site and a coagulation cascade begins as proteins called coagulation factors are activated one after the other. Eventually, a stable clot forms, preventing additional blood loss and remaining in place until the injured area has healed. The clot is then broken down when it is no longer needed. There must be an adequate amount of platelets and clotting factors and each must function normally in order for a stable clot to form.

Proteins C and protein S work together to help control blood clot formation. They inactivate specific coagulation factors (factors V and VIII) that are required to generate and form blood clots. This has the net effect of slowing down clot formation, much like brakes slow a speeding car. However, if there is not enough protein C or S or they are not functioning normally, clot formation can go unchecked, possibly leading to excessive clotting. These conditions can range from mild to severe.

Deficient or dysfunctional protein C or protein S may be due to an underlying condition (acquired), such as liver disease, kidney disease, severe infections or cancer, or can be inherited, passed from parent to child. About 1 out of every 300 people has one normal gene and one abnormal gene (heterozygous) for protein C deficiency and about 1 in 20,000 people have protein S or C deficiencies that lead to symptoms.

There are two types of inherited protein C deficiencies:

  • Type 1 is related to quantity.
  • Type 2 is related to abnormal function and is less common than Type 1.

Protein S exists in two forms in the blood: free and bound to another protein, but only the free protein S is available to combine with protein C. There are three types of inherited protein S deficiencies:

  • Type 1 deficiency is due to an insufficient quantity.
  • Type 2 is due to abnormal function.
  • Type 3 is due to low free protein S levels, though total protein S levels are normal.

Two types of tests may be used to evaluate protein C and protein S:

  • Functional tests for protein C and protein S measure their activity and evaluate their ability to regulate and slow blood clotting. Decreased activity may be due to a decreased amount of protein C or S or, more rarely, due to dysfunctional protein C or S.
  • Protein C and protein S antigen tests measure the amount of the protein present. Protein S antigen tests measure either free protein S or total protein S or both.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

You must wait at least 10 days after a thrombotic episode and be off oral warfarin (Coumadin®) anticoagulant therapy for 2 weeks before having this test done. (See also Common Questions #1.)

The Test

Common Questions

Ask a Laboratory Scientist

Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

Chen, Yi-Ben. et. al. (Updated 2013 March 3). Protein C. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003659.htm through http://www.nlm.nih.gov/. Accessed October 2014.

Gersten, T. et. al. (Updated 2012 February 8). Congenital protein C or S deficiency. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000559.htm through http://www.nlm.nih.gov/. Accessed October 2014.

Cuker, A. and Pollak, E. (Updated 2013 March 5). Protein C Deficiency. eMedicine. Available online at http://emedicine.medscape.com/article/205470-overview through http://emedicine.medscape.com. Accessed October 2014.

(Reviewed 2013 May). Protein C deficiency. Genetics Home Reference. Available online at http://ghr.nlm.nih.gov/condition/protein-c-deficiency through http://ghr.nlm.nih.gov. Accessed October 2014.

(Reviewed 2009 October). Protein S deficiency. Genetics Home Reference.Available online at http://ghr.nlm.nih.gov/condition/protein-s-deficiency through http://ghr.nlm.nih.gov. Accessed October 2014.

(© 1995-2014) Protein S Activity, Plasma. Mayo Medical Laboratories. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/80775 through http://www.mayomedicallaboratories.com. Accessed October 2014.

Sadaka, F. et al. Activated protein C in septic shock: a propensity matched analysis. Critical Care 2011, 15: R89. doi:10.1186/cc10089. Available online at http://ccforum.com/content/15/2/R89 through http://ccforum.com. Accessed October 2014.

Godwin, J. (Updated 2012 January 10). Protein S Deficiency. eMedicine. Available online at http://emedicine.medscape.com/article/205582-overview through http://emedicine.medscape.com. Accessed October 2014.

Pagana, K. D. & Pagana, T. J. (© 2012). Mosby's Diagnostic and Laboratory Test Reference 11th Edition: Mosby, Inc., Saint Louis, MO. Pp 767-768.

National Blood Clot Alliance. Protein C deficiency. Available online at http://www.stoptheclot.org/News/article136.htm through http://www.stoptheclot.org. Accessed October 2014.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Gardner, B. (2001 April 3). Protein C Deficiency. Medscape Primary Care, Pediatrics Ask the Expert [Online information]. Available online at http://www.medscape.com/viewarticle/413850_print through http://www.medscape.com.

Coagulation Test Panels. Florida Hospital Cancer Institute, Clinical and Research Laboratories [Online information]. Available online at http://www.fhci-labs.com/researchlabs/clinicallabs/hemostasisandthrombosis/panels.htm through http://www.fhci-labs.com.

Confusing Coagulation Test Names. UAB Coagulation Service, Univ of Alabama at Birmingham [Online information]. Available online at http://peir.path.uab.edu/coag/article_187.shtml and Protein C Activity, Activated Protein C Resistance (Screen for Factor V Leiden) at http://peir.path.uab.edu/coag/cat_index_14.shtml#191 through http://peir.path.uab.edu.

Schlesinger, K. and Ragni, M. (2002). DIC, Inflammation, Sepsis And Activated Protein C (APC). Transfusion Medicine Update, Issue #3 [On-line information]. Available online at http://www.annals.org/issues/v135n5/full/200109040-00013.html through http://www.annals.org.

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Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. P 781-782.

Nanda, R. (2005 April 15). Congenital protein C or S deficiency. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000559.htm. Accessed on 3/25/07.

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Nanda, R. (2005 April 15). Protein S. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003660.htm. Accessed on 3/25/07.

(© 2007). Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and Endothelial Cell Protein C Receptor. CAP [On-line information]. Available online through http://www.cap.org. Accessed on 3/25/07.

(© 2007). A Review of the Technical, Diagnostic, and Epidemiological Considerations for Protein S Assays. CAP [On-line information]. Available online through http://www.cap.org. Accessed on 3/25/07.

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Cuker, A. and Pollak, E. (Updated 2009 June 11). Protein C Deficiency. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/205470-overview through http://emedicine.medscape.com. Accessed September 2010.

(Reviewed 2009 October). Protein C deficiency. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/protein-c-deficiency through http://ghr.nlm.nih.gov. Accessed September 2010.

(Reviewed 2009 October). Protein S deficiency. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/protein-s-deficiency through http://ghr.nlm.nih.gov. Accessed September 2010.

Spence, R. et. al. (Updated 2010 January 12). Hemostatic Disorders, Nonplatelet eMedicine. [On-line information]. Available online at http://emedicine.medscape.com/article/210467-overview through http://www.nlm.nih.gov. Accessed September 2010.

Godwin, J. (Updated 2009 August 27). Protein S Deficiency. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/205582-overview through http://emedicine.medscape.com. Accessed September 2010.

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National Blood Clot Alliance. Protein C deficiency. Available online at http://www.stoptheclot.org/News/article136.htm through http://www.stoptheclot.org. Accessed September 2010.

National Blood Clot Alliance. Protein S deficiency: a clinical perspective. Available online at http://www.stoptheclot.org/News/article137.htm through http://www.stoptheclot.org. Accessed September 2010.

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