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
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).
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