Protein S deficiency
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 activate protein C in the degradation of factor Va and factor VIIIa. 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. 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 Signs and symptoms. Among the possible presentation of protein S deficiency are: Cause. 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 Protein S deficiency can also be "acquired" due to vitamin K deficiency, treatment with warfarin, liver disease, 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. 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. The diagnosis for deficiency of protein S can be done via reviewing family history of condition and genetic testing, as well as the following: Differential diagnosis. Among the possibilities for  differential diagnosis of protein S deficiency are- Antiphospholipid syndrome, disseminated intravascular coagulation and antithrombin deficiency (though this list is not exhaustive) Types. There are three types of hereditary protein S deficiency: Treatment. 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):