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At a glance

Congenital or acquired coagulation disorder 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 (liver disease, Nephrotic Syndrome, systemic lupus erythematosus, pregnancy, and disseminated intravascular coagulation).

Synonyms

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

History

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

Incidence

Mild protein S deficiency occurs in approximately 1:500. The severe form (neonatal fulminans purpura) is extremely rare.

Genetic inheritance

Autosomal dominant inheritance.

Pathophysiology

Thrombophilia due to protein S deficiency is caused by a heterozygous mutation in the gene encoding protein S on chromosome 3q11.1. Protein S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein C. Protein S exists in two forms in plasma: the free, functionally active form (40%) and the nonanticoagulant form complexed with C4-binding protein (C4BP). The anticoagulant functions of protein S are cofactor to activated protein C in regulation of FVa in prothrombinase complex, cofactor to activated protein C in regulation of FVIIIa and direct activated protein C-independent inhibition of prothrombinase complex.

Diagnosis

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

Clinical aspects

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 (30-60% of normal) manifest later with venous and, more rarely, arterial thrombosis.

Precautions before anesthesia

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 (eg, 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. Consult with hematologist. Detailed evaluation of the cardiac and cerebrovascular systems. Investigations: Full blood count, clotting studies including thromboelastography, protein S concentrations.

Anesthetic considerations

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. ...

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