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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.
Enzyme-linked immunosorbent assay (ELISA)
C4bBP levels range from 60% to 150%. Adult levels of C4bBP are generally reached at six months of age. Levels are generally undetectable in the neonate.
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.
Citrated plasma samples should be collected by double centrifugation. Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.1 Evacuated collection tubes must be filled to completion to ensure a proper blood to anticoagulant ratio.2,3 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples, except when using a winged blood collection device (ie, "butterfly"), in which case a discard tube should be used.4,5 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternate anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes. Centrifuge for 10 minutes and carefully remove 2/3 of the plasma using a plastic transfer pipette, being careful not to disturb the cells. Deliver to a plastic transport tube, cap, and recentrifuge for 10 minutes. Use a second plastic pipette to remove the plasma, staying clear of the platelets at the bottom of the tube. Transfer the plasma into a LabCorp PP transpak frozen purple tube with screw cap (LabCorp N° 49482). Freeze immediately and maintain frozen until tested. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.
Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.
Freeze. Stable at room temperature for eight hours.
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|500452||C4 Binding Protein||500453||C4 Binding Protein**||%||38522-9|