The natural anticoagulant protein S; hemostatic functions and deficiency

Abstract

Protein S (PS) is a vital endogenous anticoagulant. It plays a crucial role in regulating coagulation by acting as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. Additionally, it possesses direct anticoagulant properties by impeding the intrinsic tenase and prothrombinase complexes. Protein S oversees the coagulation process in both the initiation and propagation stages through these roles. The significance of protein S in regulating blood clotting can be inferred from the significant correlation between deficits in protein S and an elevated susceptibility to venous thrombosis. This is likely because activated protein C and tissue factor pathway inhibitor exhibit low efficacy as anticoagulants when no cofactors exist. The precise biochemical mechanisms underlying the roles of protein S cofactors have yet to be fully elucidated. Nevertheless, recent scientific breakthroughs have significantly enhanced comprehension findings for these functions. The diagnosis of protein S deficiency, both from a technical and genetic standpoint, is still a subject of debate due to the complex structural characteristics of the condition. This paper will provide an in-depth review of the molecular structure of protein S and its hemostatic effects. Furthermore, we shall address the insufficiency of protein S and its methods of diagnosis and treatment.

Plain Language Summary

What is the purpose of this summary?

• To provide an in-depth review of the molecular structure of protein S and its hemostatic effects.

• To address the deficiency of protein S and its methods of diagnosis and treatment.

What is known?

• Protein S operates as an anticoagulant through its roles as a cofactor for APC, TFPI, and an inhibitor of FIXa.

• Protein S deficiency can be either inherited or acquired.

What is new?

• Plasma protein S and platelet-derived protein S contribute to regulating coagulation and maintaining hemostasis. Protein S can be used as a potential promising treatment target for persons diagnosed with hemophilia.

Keywords:

• Deep vein thrombosis
• fibrinolysis
• protein C
• protein S
• pulmonary embolism

Acknowledgments

We acknowledge King Faisal Medical City for Southern Region (KFMCity), King Fahad Medical City (KFMC) and King Saud University (KSU) for their support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors contributions

S.A. Designed the review, wrote the manuscript and drew the figures, A.A.B and I.A.A. collected and drafted the relevant literature review part, and S.K.A. revised the manuscript.

All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

No funding for this work.