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 thromboembolism (a blood vessel blocked by a blood clot), 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
A blood sample taken from a vein in your arm
Test Preparation Needed?
No test preparation is needed.
The Test Sample
What is being tested?
Proteins C and S help adjust the rate of blood clot formation. When a blood vessel or tissue is injured, the body initiates the coagulation cascade - a step by step process involving the activation of platelets and of up to 20 protein factors - which results in the formation of a stable blood clot. This clot prevents additional blood loss and protects the injury until it heals. Once it is no longer needed other factors break the clot down so that it can be removed.
Thrombin is a clotting factor that can accelerate or decelerate blood clot formation by promoting or inhibiting its own activation. It forms a feedback loop that uses Protein C and Protein S to slow down the coagulation cascade. 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 (VTE - venous thromboembolism) and, more rarely, in the arteries.
Problems with Protein C and Protein S can be inherited or acquired.
There are two types of Protein C deficiencies:
Type 1 is related to quantity
Type 2 to abnormal function.
Protein S exists in 2 forms, free and bound, but only the free Protein S is available to combine with Protein C.
There are 3 types of Protein S deficiencies:
Type 1 deficiency is due to an insufficient quantity
Type 2 to abnormal function
Type 3 to a shift from free Protein S to bound Protein S.
Decreased Protein C and Protein S quantity may be related to insufficient production or to increased use. Since both proteins are produced in the liver and are vitamin K dependent; liver disease, a shortage of vitamin K, or anticoagulant therapy that opposes vitamin K, may result in reduced Protein C and/or Protein S levels. Conditions such as disseminated intravascular coagulation (DIC) that cause clotting and bleeding throughout the body use up clotting factors, including Protein C and Protein S, at an increased rate, and so, decrease their concentrations in the blood.
Although inherited mutations in the genes that produce Protein C and Protein S are relatively rare, they can result in:
- a decreased level of Protein C or Protein S being produced,
- an abnormal protein that either cannot bind properly to its cofactor (C or S)
- an abnormal protein which when combined, does not degrade factors VIIIa and Va normally
When these mutations occur, they are independent of each other and the mutation is most likely to be in one of Protein C or Protein S. Changes in the gene may be heterozygous (one mutated copy of the C or S gene) or homozygous (two changed copies of C or S). A heterozygous change raises the risk of developing a VTE by a moderate amount but a homozygous change in either gene can cause severe clotting – it may cause life threatening purpura fulminans or DIC in the newborn, and it requires a lifetime of vigilance against recurrent thrombotic episodes.
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?
No test preparation is needed.
Ask a Laboratory Scientist
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.