Protein C and Protein S

Tests for Protein C and Protein S may look at their function (activity) or quantity. They are usually used to help diagnose the cause of a venous thromboembolism (VTE) – especially if the blood clot is in a relatively young person (less than 50 years old) or has formed in an unusual location, such as the veins leading to the liver or kidney or cerebral veins. While immediate treatment of the VTE does not depend on the test result, your doctor will want to determine its cause and the likelihood of recurrent clotting once your condition has stabilised.
Functional tests for Protein C and free Protein S are usually requested with other tests as part of thrombophilia screen, to screen for sufficient, normal, factor activity. Based on those results, quantities of Protein C and Protein S are often measured to look for decreased production due to an acquired or inherited condition, and to classify the type of deficiency. If the shortage is due to an inherited genetic change, the quantity of Protein C or Protein S available and its degree of activity can be used to help determine whether a person is heterozygous or homozygous. Genetic testing can also be performed to determine the causative mutation, confirming the condition is inherited.
A test that shows decreased activity or quantity of Protein C or Protein S should usually be repeated on another occasion before a diagnosis is made because there are a variety of conditions that can cause temporary changes in the level and function of Proteins C and S. If an acquired deficiency is identified, Protein C or Protein S concentrations may be monitored occasionally as the underlying condition progresses – as may happen with liver disease - or, is resolved – as may happen with Vitamin K deficiency. An inherited change is usually not monitored but your doctor will keep it in mind when you are exposed to situations that increase your risk of clotting, such as surgery, chemotherapy for cancer, or oral contraceptive use.

Protein C and Protein S tests are requested when you have had a thrombotic episode, especially when you are relatively young (less than 50 years old) and/or do not have any other obvious reasons for developing a blood clot. Protein C and Protein S tests should not, however, be requested for at least 10 days after the episode and they should not be used while you are on anticoagulant therapy. Usually this means that your doctor will treat your venous thromboembolism (VTE), eliminate the immediate blood clotting threat and put you on a limited course of anticoagulant therapy (often about 3 to 6 months). During this time period, your doctor may request other tests to look for underlying diseases or conditions such as liver disease, vitamin K deficiency, or cancer, that may cause inappropriate blood clotting.
When your situation is stable (usually after you have finished the course of anticoagulation therapy), your doctor will often use Protein C and free Protein S function/activity levels, along with other tests associated with hypercoaguability, to help determine the cause of the thrombus and to help evaluate your risk of recurrence. Protein C and Protein S concentrations (quantity) may be measured with, or after, function/activity levels to determine whether a sufficient amount of each is being produced, to determine the severity of any deficiencies, and to classify the type of deficiency. When an acquired condition is identified, Protein C and/or Protein S levels may be occasionally monitored when your doctor wants to evaluate the progress or resolution of the condition (to see if the protein levels have decreased further or returned to near normal levels).
Although Protein C and Protein S tests are not recommended as routine screens, they may sometimes be measured in close relatives of someone who has an inherited Protein C or Protein S deficiency – especially if the person affected has a severe form or had their first VTE at a young age.

Elevated levels of Protein C and Protein S are not usually a problem as long as the protein is functional and, in the case of Protein S, free. If both the activity and the concentrations of Protein C and Protein S are normal, it usually indicates adequate clotting regulation. If the activity of Protein C or Protein S is low then it is likely that that protein is not functioning normally. If the protein is dysfunctional or if the quantity of Protein C or Protein S is insufficient, due to decreased production or to increased use, the coagulation cascade will not be sufficiently regulated. This increases the risk of developing a VTE, but the severity of the risk depends on how abnormal and/or how deficient the protein is.
Decreased concentrations of Protein C and Protein S may be seen with vitamin K deficiency, liver disease, severe infections (inflammatory conditions), renal disease, cancers, disseminated intravascular coagulation (DIC), HIV, during pregnancy, immediately following a thrombotic episode, and with warfarin or heparin anticoagulant therapy. These conditions reflect the decreased production or increased use of Protein C and/or Protein S. They may be mild and temporary (as with pregnancy), or have variable severity and be acute, chronic, or progressive.

If other factor deficiencies such as decreased Antithrombin, or inherited conditions, such as Factor V Leiden or Prothrombin 20210 are also present the effects of a Protein C or Protein S deficiency can be exacerbated. Fresh frozen plasma contains Protein C and Protein S and it can be used as a short term preventative when a patient is having a necessary surgical procedure. There is also a concentrate of Protein C available that can be used to provide temporary protection.

Not directly. If you have deficiencies that are due to a temporary condition (such as pregnancy or an infection) they should return to normal levels by themselves. If they are due to an underlying condition, like liver disease, that condition must be addressed. If you have inherited Protein C or Protein S deficiencies or dysfunction your doctor will often advise you to concentrate on lowering other clotting risk factors, such as lowering elevated homocysteine levels, not smoking, and avoiding oral contraceptive use. When necessary fresh frozen plasma, which contains Protein C and Protein S, can be given as a short term preventative measure (for instance before a surgical procedure) but this is not a treatment that can be used on a daily basis.