Protein S deficiency

{{Infobox medical condition (new)

| name = Protein S deficiency

| image = File:Protein PROS1 PDB 1z6c.png

| caption = Protein S structure

| pronounce =

| field =

| synonyms =

| symptoms = Purpura fulminans

| complications =

| onset =

| duration =

| types =

| causes = Vitamin K deficiency

| risks =

| diagnosis = Coagulation test

| differential =

| prevention =

| treatment = Heparin, Warfarin

| medication =

| prognosis =

| frequency =

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Protein S deficiency is a disorder associated with increased risk of venous thrombosis.{{Cite web|url=http://patient.info/doctor/protein-s-deficiency|title=Protein S Deficiency. Learn about Protein S Deficiency {{!}} Patient|website=Patient|language=en-GB|access-date=2016-10-16}} Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein C in the degradation of factor Va and factor VIIIa.{{Cite journal|date=2016-06-01|title=Protein S: Reference Range, Collection and Panels, Interpretation|url=http://emedicine.medscape.com/article/2086014-overview#showall}}

Decreased (antigen) levels or impaired function of protein S leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis. Some risk factors for deep vein thrombosis or pulmonary embolism in patients with protein S deficiency include pregnancy, older age, hormonal therapy, consumption of birth control pills, recent surgery, trauma, and physical inactivity.{{cite web |title=Protein S Deficiency |url=https://my.clevelandclinic.org/health/diseases/21877-protein-s-deficiency |website=Cleveland Clinic |access-date=7 February 2023}} 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{{medical citation needed|date=October 2016}}

Signs and symptoms

Among the possible presentation of protein S deficiency are:{{cite web|title=Congenital protein C or S deficiency: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/000559.htm|website=medlineplus.gov|access-date=16 October 2016}}

{{columns-list|colwidth=30em|

Thrombosis of lower extremities
Superficial thrombophlebitis
Redness in affected area
Purpura fulminans
Pulmonary embolism
Stroke (in children)

}}

Cause

File:Human male karyotpe high resolution - Chromosome 3 cropped.png

In terms of the cause of protein S deficiency it can be in inherited via autosomal dominance. A mutation in the PROS1 gene triggers the condition. The cytogenetic location of the gene in question is chromosome 3, specifically 3q11.1{{cite web|last1=Reference|first1=Genetics Home|title=PROS1 gene|url=https://ghr.nlm.nih.gov/gene/PROS1#location|website=Genetics Home Reference|access-date=16 October 2016}}{{cite web|last1=Reference|first1=Genetics Home|title=protein S deficiency|url=https://ghr.nlm.nih.gov/condition/protein-s-deficiency|website=Genetics Home Reference|access-date=16 October 2016}} Protein S deficiency can also be acquired due to vitamin K deficiency, treatment with warfarin, liver disease, kidney disease, chemotherapy, infection, surgery, birth control pills, pregnancy, and acute thrombosis (antiphospholipid antibodies may also be a cause as well)

Pathophysiology

In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium.{{cite web|title=Endothelial Cells, Volume 1, 1988, p158, By Una S.|url=https://books.google.com/books?isbn=0849349907|access-date=24 January 2019}}{{cite journal|title=J Clin Invest. 2009 Oct, 119(10):2942-53, Burstyn-Cohen T1, Heeb MJ, Lemke G: Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis|journal=The Journal of Clinical Investigation|volume=119|issue=10|pages=2942–53|pmid=19729839|pmc=2752078|year=2009|last1=Burstyn-Cohen|first1=T.|last2=Heeb|first2=M. J.|last3=Lemke|first3=G.|doi=10.1172/JCI39325}} Protein S is a cofactor of APC both work to degrade factor V and factor VIII. It has been suggested that Zn2+ might be necessary for Protein S binding to factor Xa.

Mutations in this condition change amino acids, which in turn disrupts blood clotting. Functional protein S is lacking, which normally turns off clotting proteins, this increases risk of blood clots.

Diagnosis

File:Blue Top.JPG

The diagnosis for deficiency of protein S can be done as part of a thrombophilia investigation, along with reviewing family history of thrombotic disease.{{cite web|title=Protein S blood test: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/003660.htm|website=medlineplus.gov|access-date=16 October 2016}}{{cite web|title=Protein S deficiency - Conditions - GTR - NCBI|url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C2676728/|website=www.ncbi.nlm.nih.gov|access-date=16 October 2016}} Testing for protein S deficiency should be delayed if there are causes for acquired deficiency or interfering factors.Marlar RA, Gausman JN, Tsuda H, Rollins-Raval MA, Brinkman HJM. Recommendations for clinical laboratory testing for protein S deficiency: Communication from the SSC committee plasma coagulation inhibitors of the ISTH. J Thromb Haemost. 2021 Jan;19(1):68-74. doi: 10.1111/jth.15109. PMID 33405382.

The initial assay for congenital protein S deficiency should be the free protein S antigen assay. If the level is low, total protein S antigen assay can be performed to differentiate between type I and type III deficiency. Protein S activity assays may be useful in patients with a normal free protein S antigen in occasional situations: 1) if no abnormality is identified during a thrombophilia workup, but clinical suspicion persists; or 2) in specific populations in which

type II deficiencies are more common.

Screening with a free protein S antigen assay is preferred because there are fewer interferences compared to assays for protein S activity, as well as better assay performance characteristics.

=Differential diagnosis=

Other causes for thrombophilia are- Antiphospholipid syndrome, Factor V Leiden and Prothrombin G20210A mutations, protein C deficiency and antithrombin deficiency (though this list is not exhaustive)

=Types=

There are three types of hereditary protein S deficiency:{{Cite journal|date=2016-05-02|title=Protein S Deficiency: Background, Pathophysiology, Epidemiology|url=http://emedicine.medscape.com/article/205582-overview#showall}}

Type I – decreased protein S activity: decreased total protein S levels, as well as decreased free protein S levels
Type II – decreased in regards to the cofactor activity of the protein
Type III – decreased protein S activity: decreased free protein S levels (normal total protein S levels)

Treatment

File:Dabigatran etexilate.svg

In terms of treatment for protein S deficiency the following are consistent with the management (and administration of) individuals with this condition (the prognosis for inherited homozygotes is usually in line with a higher incidence of thrombosis for the affected individual):{{cite journal|last1=Ten Kate|first1=M. K.|last2=Van Der Meer|first2=J.|title=Protein S deficiency: a clinical perspective|journal=Haemophilia|date=1 November 2008|volume=14|issue=6|pages=1222–1228|doi=10.1111/j.1365-2516.2008.01775.x|pmid=18479427|s2cid=26719614|language=en|issn=1365-2516|doi-access=free}}

::::::*Unfractionated heparin (w/ warfarin)

::::::*LMWH/Low molecular weight heparin

::::::*Dabigatran

::::::*Direct Factor Xa Inhibitors

::::::*Graduated compressed stocking

::::::*High degree of prophylaxis

References

External links

{{Medical resources

| DiseasesDB = 10814

| ICD10 = {{ICD10|D|68|5|d|68}}

| ICD9 = {{ICD9|289.81}}

| ICDO =

| OMIM = 176880

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 1924

| MeshID = D018455

| SNOMED CT = 1563006

}}

Category:Coagulopathies