Both protein S and protein C are dependent on vitamin K for their production and function. A deficiency of either one is associated with a tendency toward thrombosis. Protein S serves as a cofactor to enhance the anticoagulant effects of activated protein C. Slightly more than half of protein S is complexed with C4-binding protein and is inactive. Activated protein C in the presence of protein S rapidly inactivates factors V and VIII.

This test is done to differentiate acquired from congenital protein S deficiency. Congenital deficiency of protein S is associated with a high risk for thromboembolism. Acquired deficiency of protein S can be seen in various autoimmune disorders and inflammatory states owing to elevation of C4-binding protein. This protein forms an inactive complex with protein S. C4-binding protein levels should be determined in all patients who demonstrate a reduced level of protein S.

Males: 60%–130% or 0.60–1.30 of normal activity

Females (younger than 50 years): 50%–120% or 0.50–1.20 of normal activity

Newborns: 15%–50% or 0.15–0.50 of normal activity

1. Draw a 5-mL venous blood sample with a tube sodium citrate (blue-topped tube). The two-tube method is used. Label the specimen with the patient’s name, date and time of collection, and test(s) ordered.

2. Keep the specimen capped and on ice. Place in a biohazard bag and take to the laboratory immediately.

1. Decreased values are associated with protein S deficiency. Familial protein S deficiency is associated with recurrent thrombosis. Abnormal plasma distribution of protein S occurs in functional protein S deficiency. In type I, free protein S is decreased, although the level of total protein may be normal; in type II, total protein is markedly reduced.

2. Hypercoagulable-state acquired protein S deficiency is found in:

   1. Diabetic nephropathy

   2. CKD caused by hypertension

   3. Cerebral venous thrombosis

   4. Coumarin-induced skin necrosis

   5. DIC

   6. Thrombotic thrombocytopenia purpura

   7. Acute inflammation

Pretest Patient Care

1. Explain test purpose and procedure.

2. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

The following factors cause decreased protein S:

1. Heparin therapy or specimen contaminated with heparin

2. Patient on unstable warfarin (Coumadin should be discontinued for 30 days for a true protein S determination)

3. Pregnancy

4. Contraceptives (oral)

5. First month of life

6. L-Asparaginase therapy