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Protein S

Alexey Kryvenko, medical expert
Last reviewed: 04.07.2025

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Reference values (norm) for the concentration of total protein S in blood plasma are 60-140%, free - 65-144%.

Protein S is a vitamin K-dependent plasma glycoprotein. It circulates in the blood in two forms: free (40%) and bound to the C4 _component of complement (60%). They are in dynamic equilibrium, but only the free protein is active. Protein S is a cofactor of protein C in the process of inactivation of Va and VIIIa blood coagulation factors. Currently existing test systems based on ELISA allow determining the concentration of free protein S, which is of primary importance for clinical practice.

The content of protein S in the blood of men is higher than that of women. Indirect anticoagulants affect it less than protein C, this is due to the fact that protein S is synthesized in the endothelial cells of the liver and megakaryocytes. In liver diseases, its level is higher than protein C. Due to the fact that the main part of protein S is associated with the C ₄ component of complement, with an increase in the concentration of C ₄ (acute phase of inflammatory diseases or exacerbation of chronic diseases), the amount of free protein S decreases. A decrease in the concentration of protein S in the blood is possible in nephrotic syndrome due to its loss.

Classification of protein S deficiency

Type I - total protein S deficiency.
Type II - deficiency of free protein S with normal or borderline levels of total protein S.
Type III - protein S dysfunction with impaired anticoagulant activity.

Protein S deficiency leads to the development of venous thrombosis, especially in young people.

Anticoagulant system parameters and risk factors for thrombohemorrhagic complications

The indicators under study	Norm,%	Deviation of the studied parameters,%
ATIII	80-120	<80 - high risk factor for thrombosis >120 - high risk factor for hemorrhages
Protein C	70-130	<70 - high risk factor for thrombosis
Protein S	60-140	<60 - high risk factor for thrombosis

Main points of application of anticoagulant action

Anticoagulants

Phases of plasma hemostasis

Inhibitable factors of the blood coagulation system

ATIII

Protein C

Protein S

Heparin:

Low concentrations;

High concentrations

Indirect anticoagulants

I, II

I, II,

II,I

I, II

Xa, XIIa, IXa

Va, VIIIa

IXa, VIII, Xa, IIa

For all factors and platelet aggregation

Vitamin K-dependent factors - II, VII, IX, X

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