Protein C and Protein S
- 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)

This page was fact checked by our expert Medical Review Board for accuracy and objectivity. Read more about our editorial policy and review process.
.At a Glance
Why Get Tested?
To help investigate the cause of a blood clot (thromboembolism), such as a deep vein thrombosis (DVT) or pulmonary embolism (PE); 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, especially when you don’t have classic risk factors, have a blood clot at a young age (younger than age 50) or in an unusual location; 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 until your blood clot has been treated and resolves before having this test done. You may also be instructed to discontinue anticoagulant therapy. Follow any instructions you are given by your health care practitioner.
You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.
Testing.com is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.
The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.
If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.
Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.
While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”
For more information, please read the article Reference Ranges and What They Mean.
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 (antigen tests) and evaluate whether they are performing their proper functions (activity tests).
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 sufficient clotting factors and each must function normally in order for a stable clot to form.
Proteins S acts as a principal cofactor to protein C. The two work together to help regulate and control blood clot formation by inactivating 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. Therefore, 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. Both protein C deficiency and protein S deficiency are inherited in an autosomal dominant pattern. About 1 out of every 200-500 people has one normal gene and one abnormal gene (heterozygous), causing protein C deficiency. About 1 in 500 people have protein S deficiency due to heterozygous gene mutation.
There are two types of inherited protein C deficiencies:
- Type 1 is related to insufficient 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 be a cofactor for 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 decreased free protein S levels, though total protein S levels are normal.
Common Questions
View Sources
Sources Used in Current Review
(14 August 2018) Protein C and Protein S Tests. MedlinePlus. Available online at https://medlineplus.gov/lab-tests/protein-c-and-protein-s-tests/. Accessed on April 18, 2019.
(Jan. 4, 2019) Protein C Deficiency. Medscape. Available online at https://emedicine.medscape.com/article/205470-overview. Accessed on April 18, 2019.
(©2019) Protein S Deficiency. Indiana Hemophilia & Thrombosis Center. Available online at https://www.ihtc.org/protein-s-deficiency/. Accessed on April 21, 2019.
Blood Clots. American Society of Hematology. Available online at https://www.hematology.org/Patients/Clots/. Accessed on April 21, 2019.
(©2019) Protein C (Blood). University of Rochester Medical Center. Available online at https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=protein_c_blood. Accessed on April 21, 2019.
(©2019) Protein C Activity, Plasma. Mayo Clinic Laboratories. Available online at https://hematology.testcatalog.org/show/CFX. Accessed on April 22, 2019.
(©2019) Protein S Activity, Plasma. Mayo Clinic Laboratories. Available online at https://hematology.testcatalog.org/show/S_FX. Accessed on April 22, 2019.
(2016) Protein C Deficiency. National Organization for Rare Disorders. Available online at https://rarediseases.org/rare-diseases/protein-c-deficiency/. Accessed on April 22, 2019.
(October 2009) Protein C Deficiency. Genetics Home Reference. Available online at https://ghr.nlm.nih.gov/condition/protein-c-deficiency#statistics. Accessed on April 22, 2019.
(October 18 2018) Congenital Protein C or S Deficiency. MedlinePlus. Available online at https://medlineplus.gov/ency/article/000559.htm. Accessed on April 22, 2019.
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.
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.
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.
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.
Chapter 132 Thrombotic Disorders, General. The Merck Manual of Diagnosis and Therapy, Section 11. Hematology And Oncology [Online information]. Available online at http://www.merck.com/pubs/mmanual/section11/chapter132/132a.htm.
Protein C Deficiency. University of Illinois – Urbana/Champaign, Carle Cancer Center, Hematology Resource Page, Patient Resources [On-line information]. Available online at http://www-admin.med.uiuc.edu/hematology/PtProtC.htm.
Protein S Deficiency. University of Illinois – Urbana/Champaign, Carle Cancer Center, Hematology Resource Page, Patient Resources [On-line information]. Available online at http://www-admin.med.uiuc.edu/hematology/PtProtS.htm.
Bardi, J. (2002). Mysteries of a Therapy Unveiled. The Scripps Research Institute, News & Views [On-line Newsletter]. Available online at http://www.scripps.edu/newsandviews/e_20020617/print-ruf.html.
Elstrom, R. (2001 October 28, Updated). Protein C. MedlinePlus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003659.htm.
Elstrom, R. (2001 October 28, Updated). Protein S. MedlinePlus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003660.htm.
Coagulation Test Panels. Clinical and Research Laboratories, Florida Hospital Cancer Institute [On-line information]. Available online at http://www.fhci-labs.com/researchlabs/clinicallabs/hemostasisandthrombosis/panels.htm.
Laposata, M. & Vancott, E. (2000 January). How to work up hypercoagulability. CAP In the News [On-line Coagulation Case Study]. Available online at http://www.cap.org/CAPToday/casestudy/coag5.html.
Venomous Bites and Stings. The Merck Manual of Medical Information-Home Edition, Section 24. Accidents and Injuries, Chapter 287 [On-line information]. Available online at http://www.merck.com/mrkshared/mmanual_home/sec24/287.jsp.
Menta, S. (1999 Spring). The Coagulation Cascade. Physiology Disorders Evaluation, College of Medicine, Univ of Florida [On-line information]. Available online at http://www.medinfo.ufl.edu/year2/coag/title.html.
Bauer, K. (2001). The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications. Ann Intern Med. 2001;135:367-373 [Journal]. Available online through http://www.annals.org.
DeLoughery, T. (1999 March 15). Tests of Hemostasis and Thrombosis. OHSU [Online student handout]. Available online at http://www.ohsu.edu/som-hemonc/handouts/deloughery/printtest.html.
(2001 January 10, Modified). Coagulation Test Descriptions. Clinical Coagulation Laboratory, A division of Duke University Regional Referral Laboratory Services [Online information]. Available online at http://pathology.mc.duke.edu/coag/TestDes.htm.
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.
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. 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. 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. 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. 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. 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.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 922-923, 926-927.
National Blood Clot Alliance. Protein C deficiency. Available online at http://www.stoptheclot.org/News/article136.htm. Accessed September 2010.
National Blood Clot Alliance. Protein S deficiency: a clinical perspective. Available online at http://www.stoptheclot.org/News/article137.htm. Accessed September 2010.
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. 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. 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. Accessed October 2014.
(Reviewed 2013 May). Protein C deficiency. Genetics Home Reference. Available online at http://ghr.nlm.nih.gov/condition/protein-c-deficiency. Accessed October 2014.
(Reviewed 2009 October). Protein S deficiency. Genetics Home Reference.Available online at http://ghr.nlm.nih.gov/condition/protein-s-deficiency. Accessed October 2014.
(© 1995-2014) Protein S Activity, Plasma. Mayo Medical Laboratories. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/80775. 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. Accessed October 2014.
Godwin, J. (Updated 2012 January 10). Protein S Deficiency. eMedicine. Available online at http://emedicine.medscape.com/article/205582-overview. 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. Accessed October 2014.
Ask a Laboratory Scientist
