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).
References:
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.
