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Confirmation and characterization of protein S (PS) deficiency: C4b-binding protein elevates as an acute phase protein that may lead to enhanced protein S binding and decreased free protein S levels.
Cloudy or lipemic samples may lead to overestimation of the C4bBP antigen.6 Interference by rheumatoid factor cannot be excluded.
This procedure may be considered by Medicare and other carriers as investigational and, therefore, may not be payable as a covered benefit for patients.
In blood, PS exists in a free and bound state. Sixty percent to 70% of plasma protein S circulates complexed to C4b-binding protein (C4bBP), a 570 kilodalton complement system regulator.6 The remaining protein S, called free PS, in molar excess to C4bBP, is the functionally active form of PS. Acquired protein S deficiency may be, theoretically, the result of elevated plasma C4bBP, decreased synthesis of protein S synthesis, or increased protein S consumption/loss. C4bBP is an acute phase reactant, thus, its plasma concentration increases with inflammation and hormonal changes, resulting in increased protein S binding and a theoretically relative deficiency of free protein S. Acquired deficiency of free protein S due to acute phase elevation of C4b binding protein has been disputed.7 C4bBP is elevated in inflammation, pregnancy, estrogen and progestin administration, diabetes mellitus, systemic lupus erythematosus, AIDS, renal allograft rejection, and smoking. Functional protein S synthesis is diminished in vitamin K deficiency, liver disease, with some chemotherapy agents, warfarin therapy, and L-asparaginase therapy. Protein S consumption occurs in acute thrombosis, polycythemia vera, sickle cell disease, essential thrombocythemia, and disseminated intravascular coagulation.
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Colman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis, Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2000.
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