What is Protein S test? 

Protein S test determines the level of the glycoprotein (a protein with an attached carbohydrate), protein S, in your blood. 

Protein S is dependent on vitamin K for its action and is primarily synthesised in the liver and the endothelial cells in small quantities. It acts with the activated protein C (another glycoprotein) to inactivate the procoagulant (promote blood clotting) factors Va and VIIIa. Thus, preventing blood clotting in the body. About 60% of protein S is bound to C4b binding protein while the remaining is in free form. It is the free form of protein S that has anticoagulant activity.

Those who have a deficiency of this protein tend to get unexplained and excessive blood clots. The deficiency is usually inherited but it may also be acquired. It could be mild to severe.

Protein S deficiency makes you prone to a condition called deep vein thrombosis (DVT). The latter is characterised by the formation of blood clots in the deeper veins of arms and legs. The clots move throughout the body and if they reach your lungs, they can cause a life-threatening condition called pulmonary embolism. Most people with mild protein S deficiency may never develop abnormal blood clots.

Certain factors can increase the risk of serious blood clots in people with mild protein S deficiency. These include:

  • Surgery
  • Advancing age
  • Pregnancy
  • Immobility
  • Combination of other clotting disorders with protein S deficiency

The severe form of this condition is quite rare. In infants with severe deficiency, blood clots may form in small blood vessels throughout the body and prevent blood flow to the tissues, leading to tissue necrosis (death of the body tissue). Due to extensive clotting of blood, the available clotting proteins are used up. This results in abnormal bleeding in various parts of the body that is seen as large purple lesions on the skin. This condition is called purpura fulminans. Individuals who survive this condition as newborns may experience recurrent attacks of purpura fulminans throughout life.

Acquired protein S deficiency may result from increased usage of protein S in the body or decreased production of protein S in the liver. 

  1. Why is a Protein S test performed?
  2. How do you prepare for a Protein S test?
  3. How is a Protein S test performed?
  4. Protein S test results and normal range
Doctors for Protein S Test

The test is performed to detect protein S deficiency. It helps to determine the cause of deep vein thrombosis. Your doctor may order this test in the following conditions:

  • If you have an unexplained blood clots 
  • If you have a family history of clotting disorders
  • If you are below 50 years of age and have a blood clot in your body
  • If you have a clot at an unusual location, such as blood vessels of the brain, kidney or liver
  • If you have had repeated miscarriages

Also, this test can be used to screen for protein S deficiency in those with a family history of the condition.

A doctor may order a protein S test for newborns who are suspected of having clotting disorders, such as purpura fulminans. 

If an acquired deficiency is diagnosed, this test may be ordered occasionally to monitor the progress of the condition.

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Inform your doctor if you are taking any medicines or supplements. He/she may tell you to discontinue some medicines before the test. This is because, drugs such as blood thinners, birth control pills and medicines given for hormone replacement therapy can alter the results. If you have had a recent clotting episode, your doctor may wait for at least 10 days before ordering this test.

A blood sample is required for this test. The sample will be drawn from a vein in your arm. The procedure usually takes just a few minutes. 

After the test, a small bruise may develop at the puncture site. It will go away on its own. If you notice an infection developing at the site, please talk to your doctor.

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Normal results:

Normal values of protein S in the blood are as follows:

  • Males: 60%-130% of normal activity
  • Females: 50%-120% of normal activity
  • Newborns: 15%-50% of normal activity

Your results may show a slight variation depending on:

  • Your health history
  • Your gender
  • Your age
  • The method used to perform the test

Discuss your results with your doctor to know what they mean.

Abnormal results:

Decreased protein S levels are reported as abnormal and may be due to an inherited or acquired protein S deficiency.

Acquired protein S deficiency may occur in the following conditions:

  • Chronic renal failure due to hypertension
  • Cerebral venous thrombosis
  • Coumarin-induced skin necrosis
  • Diabetic nephropathy
  • Acute inflammation
  • Disseminated intravascular coagulation (a condition where multiple small blood clots form throughout the bloodstream)
  • Thrombotic thrombocytopenic purpura (a disorder in which blood clots form throughout the body and lower the platelet count)
  • Liver disease
  • Vitamin K deficiency
  • Sickle cell disease
  • Conditions causing simultaneous clotting and bleeding in the body
  • Severe inflammatory infections
  • HIV/AIDS infection
  • Cancers
  • Kidney disease
  • Pregnancy
  • Birth control pills
  • Anticoagulants (blood thinners) that oppose vitamin K
  • Long-term antibiotic use

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational point of view and is in no way a substitute for medical advice by a qualified doctor.

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References

  1. University of Rochester Medical Center [Internet]. Rochester (NY): University of Rochester Medical Center; Protein S (Blood)
  2. Genetics Home Reference [internet]. National Institute of Health: US National Library of Medicine. US Department of Health and Human Services; Protein S deficiency
  3. Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlbäck B, et al. Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A. 1986 Sep. 83(18):6716-20. PMID: 2944113
  4. Francis RB Jr. Protein S deficiency in sickle cell anemia. J Lab Clin Med. 1988 May;111(5):571-6. PMID: 2966224.
  5. Kemkes-Matthes B. Acquired protein S deficiency. Clin Investig. 1992 Jun;70(6):529-34. PMID: 1392420
  6. Van Cott EM, Soderberg BL, & Laposata M. Hypercoagulability test strategies in the protein C and protein S pathway. Clin Lab Med. 2002; 22(2):391-403. PMID: 12134467
  7. Murdock, P.J., Brooks, S., Mellars, G., et al. A simple monoclonal antibody based ELISA for free Protein S. Comparison with PEG precipitation. Clin Lab Haematol. 1997 Jun;19(2):111-4. PMID: 9218150.
  8. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med. 2004 Oct 7. 351(15):1548-63. PMID: 15470219.
  9. Chernecky CC, Berger BJ. Protein S, total and free – blood. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures. 6th ed. St Louis, MO: Elsevier Saunders; 2013: p 928-930.
  10. Anderson JA, Hogg KE, Weitz JI. Hypercoagulable states. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018: chap 140.
  11. National Health Service [internet]. UK; Blood Tests
  12. Fischbach FT. Manual of Laboratory and Diagnostic Tests, 7th ed, 2003 Lippincott Williams & Wilkins Publishers pp 111
  13. Merck Manual Consumer Version [Internet]. Kenilworth (NJ): Merck & Co. Inc.; c2018. Disseminated Intravascular Coagulation (DIC)
  14. Merck Manual Consumer Version [Internet]. Kenilworth (NJ): Merck & Co. Inc.; c2018. Thrombotic Thrombocytopenic Purpura (TTP)
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