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Congenital or acquired control of the clotting mechanism resulting in a widespread thrombotic tendency. Protein S is a nonenzymatic, vitamin K-dependent cofactor of activated protein C. It is either inherited or acquired and leads to liver disease, nephrotic syndrome, systemic lupus erythematosus, pregnancy, and disseminated intravascular coagulation.

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Protein S alpha Deficiency; Protein S Pseudogene; Purpura fulminans.

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Three types of protein S deficiency are described:

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  • Type I: reduced production
  • Type II: abnormality of C4bBP
  • Type III: functionally abnormal Protein S.

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Protein S deficiency was first identified in 1979 in Seattle, United States, and arbitrarily named after the city of this discovery.

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Unknown; one study found 8% of 179 patients with a positive family history or who had spontaneous thrombosis to be deficient in protein S.

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Autosomal dominant inheritance with male-to-male transmission observed. Gene map locus is 3p11.1-q11.2. Additional factors are necessary to precipitate thrombosis because some family members of the affected are asymptomatic even though they have equally low levels of protein S and because there are instances of a skipped generation.

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Protein S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein C. Deficiency of protein S causes thrombotic disease. Protein S exists in two forms in plasma: the free, functionally active form (40%) and the inactive form complexed with C4b-binding protein (C4bBP).

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Familial history of thromboembolic events at a young age. Low plasma protein S levels.

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Deficiency of protein S manifests as severe recurrent thromboembolic disease (leg vein thrombosis, pulmonary embolism, superficial thrombophlebitis, and thrombosis in uncommon sites—axillary, mesenteric, and cerebral veins). While patients with homozygous deficiency present as neonatal purpura fulminans, those with heterozygous forms (30 to 60% of normal) manifest later with venous and, more rarely, arterial thrombosis.

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Protein S deficiency does not cause abnormalities in the routine screening coagulation tests; a high index of suspicion is necessary in case of familial or personal history of thrombotic events at a young age and in patients at risk for acquired protein S deficiency (e.g., nephrotic syndrome). Preventive measures, such as low-molecular-weight heparin to prevent deep venous thrombosis, should be instituted before operation and continued postoperatively until the patient is ambulant. Initiation of oral anticoagulation therapy without antecedent heparin therapy is fraught with risks of worsening of thrombotic tendencies. Detailed evaluation of the cardiac and cerebrovascular systems. Investigations: complete blood count, clotting studies including thromboelastography, protein S levels.

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If a locoregional anesthetic technique is used, the timing of its performance (and of the withdrawal of the catheter) should be adapted to the timing of low-molecular-weight heparin therapy. Use heparin-bonded central venous catheter to reduce the risk of central venous thrombosis. Arterial catheters should be removed as soon as possible.

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The use of antifibrinolytics (e.g., ε-aminocaproic acid) is contraindicated because ...

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