Protein C and Protein S

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Formal name: Protein C, Functional or Antigen; Protein S, Functional or Antigen (Free or Total)

At a Glance

Why Get Tested?

To help evaluate a thrombotic episode; to determine whether you may have an inherited or acquired Protein C or Protein S deficiency

When to Get Tested?

When you have had an unexplained blood clot (thromboembolism); when your newborn has a severe clotting disorder, such as disseminated intravascular coagulation (DIC) or purpura fulminans; 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 anticoagulant therapy for 2 weeks before having this test done.

The Test Sample

What is being tested?

The tests for protein C and protein S are separate tests that are usually performed as part of the investigation of a possible clotting disorder. The tests measure the amount of each protein and evaluate whether they are performing their proper function in the body.

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 is initiated, with clotting factors being activated one after the other. As the cascade nears completion, fibrinogen is converted by thrombin into insoluble fibrin threads that crosslink together to form a fibrin net that stabilizes at the injury site. The fibrin net adheres to the site of injury along with the platelets to form a stable blood clot. This barrier prevents additional blood loss and remains in place until the injured area has healed. There must be an adequate amount of platelets and of each of the coagulation factors and each must function normally in order for a stable clot to form.

Proteins C and S help regulate blood clot formation. They work together in a feedback system with thrombin, a clotting factor that can accelerate or decelerate blood clot development. Thrombin first combines with a protein called thrombomodulin, then activates Protein C. This activated Protein C (APC) then combines with Protein S (a cofactor), and together they work to degrade coagulation factors VIIIa and Va (these activated factors are required to produce thrombin). This has the net effect of slowing down the generation of new thrombin and inhibiting further clotting. If there is not enough protein C or protein S, or if either one is not functioning normally, then thrombin generation goes on largely unchecked. This can lead to excessive or inappropriate clotting that may block the flow of blood in the veins and, rarely, in the arteries (thrombosis).

Problems with Protein C and Protein S can be passed from parent to child (inherited) or may be due to an underlying condition or disease (acquired).

There are two types of Protein C deficiencies:

  • Type 1 is related to quantity.
  • Type 2 to abnormal function.

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

  • Type 1 deficiency is due to an insufficient quantity.
  • Type 2 to abnormal function.
  • Type 3 to an increased clearance of free 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 concentration 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 works with protein C. It is present in the blood in two forms, free or bound to another protein, but only the free form is available to combine with protein C. Protein S antigen tests measure either free protein S or total protein S.

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 anticoagulant therapy for 2 weeks before having this test done.

The Test

Common Questions

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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

Dugdale, D. et. al. (Updated 2009 March 2). Protein C. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003659.htm. Accessed September 2010.

Dugdale, D. et. al. (Updated 2010 March 28). Congenital protein C or S deficiency. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000559.htm. Accessed September 2010.

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.

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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.

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 781-782.

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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. 

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

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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.

Nanda, R. (2005 April 15). Protein C. MedlinePlus [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003659.htm. Accessed on 3/25/07. 

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.