Protein S deficiency
Encyclopedia
Protein S deficiency is a disorder associated with increased risk of venous thrombosis
. Protein S, a vitamin K
-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activated protein C in the proteolytic degradation of factor V
a and factor VIII
a. Decreased (antigen) levels or impaired function (activity) of protein S
leads to decreased degradation of factor V
a and factor VIII
a and an increased propensity to venous thrombosis. Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while the remaining 40 percent is free. Only free protein S has activated protein C cofactor activity.
Protein S deficiency can also be acquired due to vitamin K deficiency or treatment with warfarin
, systemic sex hormone therapy and pregnancy, liver disease, and certain chronic infections (for example HIV). Vitamin K deficiency or treatment with warfarin
generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis.
Protein S deficiency is the underlying cause of a small proportion of cases of disseminated intravascular coagulation
(DIC), deep venous thrombosis (DVT) and pulmonary embolism
(PE).
Hereditary PSD is an autosomal dominant condition, resulting in a 50 percent chance of passing the disease to offspring. Less than half of those diagnosed with PSD will experience thrombosis
, and those who do usually are affected only from the age of the late teens onwards. Screening of young children is usually deferred because early testing is often inaccurate, and it is better to wait until they are old enough to decide for themselves whether they want to be tested
Venous thrombosis
A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. (Thrombosis is a medical term for blood clotting (Haemostasis) occurring in the wrong place, i.e...
. Protein S, a vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activated protein C in the proteolytic degradation of factor V
Factor V
Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor...
a and factor VIII
Factor VIII
Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
a. Decreased (antigen) levels or impaired function (activity) of protein S
Protein S
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
leads to decreased degradation of factor V
Factor V
Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor...
a and factor VIII
Factor VIII
Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
a and an increased propensity to venous thrombosis. Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while the remaining 40 percent is free. Only free protein S has activated protein C cofactor activity.
Types
There are three types of hereditary protein S deficiency:- Type I - decreased proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
S activity: decreased total protein S (=both bound and free protein S) levels AND decreased free protein SProtein SProtein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
levels (quantitative defect) - Type II - decreased protein S activity: normal free protein S levels AND normal total protein S levels (qualitative defect)
- Type III - decreased protein S activity: decreased free protein S levels AND normal total protein S levels (quantitative defect)
Protein S deficiency can also be acquired due to vitamin K deficiency or treatment with warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, systemic sex hormone therapy and pregnancy, liver disease, and certain chronic infections (for example HIV). Vitamin K deficiency or treatment with warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis.
Protein S deficiency is the underlying cause of a small proportion of cases of disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
(DIC), deep venous thrombosis (DVT) and pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE).
Hereditary PSD is an autosomal dominant condition, resulting in a 50 percent chance of passing the disease to offspring. Less than half of those diagnosed with PSD will experience thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, and those who do usually are affected only from the age of the late teens onwards. Screening of young children is usually deferred because early testing is often inaccurate, and it is better to wait until they are old enough to decide for themselves whether they want to be tested
External links
- Protein S Deficiency And Thrombophilia at proteinsdeficiency.com
- Protein S Deficiency -- University of Illinois