Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (1179 page)

   
Normal range:
“free” or “total.”

   Free protein S (measured functionally): 60–140% in males, slightly lower in females but increases with age.

   Total protein S (measured as antigen by enzyme immunoassay): 60–140%, lower in females but increases with age.

   During the first year of life, the total PS is low (free PS level is identical with that of adults). Adult levels of total PS are reached by 1 year of life.

   Use

   Protein S, both free and total, should be requested in patients with unprovoked venous thrombosis suspected of congenital thrombophilia.

   Protein S should not be performed in patients on vitamin K antagonist therapy. It is necessary to wait for 2 weeks after cessation of therapy.

   It is advisable to request protein S together with protein C, because both are affected by therapy with vitamin K antagonists, but they have different half-lives. Comparing the two facilitates the interpretation.

   If the functional assay for free protein S is decreased, an immunoassay for free protein S is recommended for confirmation.

   Interpretation

Decreased In

   Congenital condition. Prevalence of the congenital deficiency of protein S is 1 in 500 for the Caucasian population. It predisposes to venous thromboembolism. The rare homozygous type may cause severe neonatal purpura fulminans.

   Acquired: oral anticoagulants or vitamin K deficiency; pregnancy, hormone replacement therapy, oral contraceptives; young age; liver disease; acute-phase reaction situations (decreased free protein S but increased total protein S); proteinuria; DIC; and
L
-asparaginase therapy

   Limitations