Reference Values During Pregnancy

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Protein S, total (plasma)


Nonpregnant Adult First Trimester Second Trimester Third Trimester


70 -140 39 - 105 27 - 101 33 - 101

Protein S is a vitamin K dependent protein that is a cofactor for activated protein C (APC)-mediated degradation of coagulation factors Va and VIIIa, It also appears to act as a cofactor for tissue factor pathway inhibitor (TFPI), inhibiting tissue factor–mediated factor X activation. Protein S binds with high affinity to  C4b binding protein (C4bBP) in plasma, with the excess circulating as free protein S (the predominantly active form).

Protein S deficiency is defined by its decreased APC-cofactor activity. Protein S deficiency has been associated with a increased lifetime risk of venous and possibly arterial thrombosis. Protein S deficiency may be inherited or acquired.

Inherited protein S deficiency is an autosomal dominant disease characterized by low protein S activity and is of three types:

  • Type I protein S deficiency has a decrease in the level of free and total protein S.
  • Type II (also called IIb)  deficiency  is uncommon and has a normal total and free antigen levels.
  • Type III (also called IIa) deficiency is characterized by low free protein S levels and normal  total protein S

Type I and type III  account for 95% of inherited cases.

Acquired deficiencies of protein S are more common than inherited protein S deficiency. Some causes of acquired protein S deficiency include vitamin K deficiency,  consumption from thrombosis, DIC, or invasive procedures, decreased hepatic synthesis, pregnancy, estrogen, sickle cell anemia, HIV infection, varicella infection, nephrotic syndrome, and acute phase reactions (due to elevated C4b-binding protein).


1. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009 Dec;114(6):1326-31. PMID:19935037
2. Khor B, Van Cott EM.Laboratory evaluation of hypercoagulability. Clin Lab Med. 2009 Jun;29(2):339-66.>PMID:19665682
3.Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.

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