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| {{CMG}}; {{AE}}{{RAK}}
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| ==Overview== | | Cardiac surgery<ref name="pmid23447502">{{cite journal| author=Aya HD, Cecconi M, Hamilton M, Rhodes A| title=Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis. | journal=Br J Anaesth | year= 2013 | volume= 110 | issue= 4 | pages= 510-7 | pmid=23447502 | doi=10.1093/bja/aet020 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23447502 }} </ref> |
| Protein S deficiency is an autosomal dominant thrombophilia, which leads to an increased risk of thromboembolic events. Protein S is a vitamin K-dependent glycoprotein and plays a role in anticoagulation. It is mainly a cofactor to the activated protein C (APC), which inactivates coagulation factors Va and VIIa and thereby controlling the coagulation cascade.
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| ==Historical Perspective== | |
| Protein S was first discovered and purified in Seattle, Washington in 1979, and it was arbitrarily named protein S after the city it was discovered in. The function of this protein was still unknown; however, it was hypothesized that protein S plays a role in activating protein C. Protein S deficiency was first discovered in 1984 when two related individuals with recurrent thromboembolic events and normal coagulation tests were studied. At the time, protein C deficiency was usually associated with recurrent familial thrombosis. These individuals were found to have diminished anticoagulation activity with normal coagulation tests (including a normal protein C level), and when purified human protein S was added to their plasma, effective anticoagulation was restored. (1)
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| [Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
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| The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
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| In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
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| In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
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| There have been several outbreaks of [disease name], including -----.
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| In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
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| ==Classification== | |
| Protein S deficiency can be subdivided into three types depending on whether the abnormality affects total protein S level, free protein S level, and/or protein S function:
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| *'''Type I:''' Reduced total protein S, free protein S, and protein S function
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| It is the classic form of hereditary protein S deficiency. Total protein S levels drop to approximately 50% of normal values while free protein S levels collapse to almost 15% of the normal. On a genetic level, type I deficiency usually results from missense or nonsense mutations. On few occasions, microinsertions, microdeletions, and splice site mutations have occurred with this type.
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| *'''Type II:''' Normal total and free protein S, reduced protein S function
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| This form results from a qualitative defect and is very rare. Reports describe missense mutations that affect the protein's ability to bind to activated protein C. (2,3,4)
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| These mutations may alter the conformation of protein S or interfere with carboxylation of the gamma-carboxyglutamic acid domain of the protein. In a series of 118 French patients with thromboembolism associated with protein S deficiency, 26 had a serine to proline substitution at amino acid 460 (the Heerlen polymorphism), which affects protein S metabolism. The low free plasma protein S may result from increased binding of the abnormal protein S to C4b-binding protein [38,39]. The thrombophilic risk with this polymorphism has been questioned.
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| *'''Type III:''' Normal total protein S, reduced free protein S and protein S function
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| This is a quantitative defect.
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| {| class="wikitable sortable"
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| !Type
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| !Total Protein S
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| !Free Protein S
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| !Protein S Function
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| |-
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| |I
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| |↓
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| |↓
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| |↓
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| |-
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| |II
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| |↔
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| |↔
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| |↓
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| |-
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| |III
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| |↔
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| |↓
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| |↓
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| |}
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| ==Pathophysiology==
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| ==Clinical Features==
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| ==Differentiating [disease name] from other Diseases==
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| ==Epidemiology and Demographics==
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| ===Age===
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| ===Gender===
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| ===Race===
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| ==Risk Factors== | |
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| == Natural History, Complications and Prognosis==
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| == Diagnosis ==
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| ===Diagnostic Criteria===
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| === Symptoms ===
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| === Physical Examination ===
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| === Laboratory Findings ===
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| ===Imaging Findings===
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| === Other Diagnostic Studies ===
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| == Treatment ==
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| === Medical Therapy ===
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| === Surgery ===
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| === Prevention ===
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| ==References==
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| {{Reflist|2}}
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