What is protein S deficiency?

Updated: Jan 03, 2021
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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Protein S is a vitamin K–dependent anticoagulant protein that was first discovered in Seattle, Washington in 1979 and arbitrarily named after that city. The major function of protein S is as a cofactor to facilitate the action of activated protein C (APC) on its substrates, activated factor V (FVa) and activated factor VIII (FVIIIa). 

Protein S deficiency usually manifests clinically as venous thromboembolism (VTE). [1]  Any association of protein S deficiency with arterial thrombosis appears coincidental or weak at best. Evidence for arterial thrombosis in other hereditary thrombophilias (eg, protein C deficiency, antithrombin III deficiency, or factor V Leiden gene mutation) also appears to be minimal. [2]

Protein S deficiency may be hereditary or acquired; the latter is usually due to hepatic disease, nephrotic sydrome, or vitamin K deficiency. Protein S and C levels are lower in sickle cell anemia and they decrease further significantly during crisis. [3]

Hereditary protein S deficiency is an autosomal dominant trait. Thrombosis is observed in both heterozygous and homozygous genetic deficiencies of protein S.

Protein S deficiency is primarily diagnosed using  laboratory tests that detect free protein S antigen, and less commonly by measuring functional protein S activity (based on clotting assays); see Workup. Management is required in the event of acute VTE and includes administration of a low molecular weight heparin (LMWH), a vitamin K antagonist, or a direct oral anticoagulant (DOAC). Prophylaxis may be used in selected patients who are asymptomatic carriers without a thrombotic event. (See Treatment and Medication.)

For patient education information, see the Deep Vein Thrombosis Health Center and What Is Thrombophilia?.

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