Turnaround Time: 4 - 8 days
CPT Code:


Test Type: 2 mL Plasma, Frozen
Stability Time:

Stable at room temperature for eight hours.

Reference Range:

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.


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.

1. Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin Pathol. 1997 Jan; 107(1):105-110. PubMed 8980376

2. Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant. Am J Clin Pathol. 1998 Jun; 109(6):754-757. PubMed 9620035

3. National Committee for Clinical Laboratory Standardization. Collection, Transport, and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline. 5th ed. Villanova, Pa: NCCLS; 2008. Document H21-A5:28(5).

4. Gottfried EL, Adachi MM. Prothrombin time and activated partial thromboplastin time can be performed on the first tube. Am J Clin Pathol. 1997 Jun; 107(6):681-683. PubMed 9169665

5. McGlasson DL, More L, Best HA, Norris WL, Doe RH, Ray H. Drawing specimens for coagulation testing: Is a second tube necessary? Clin Lab Sci. 1999 May-Jun; 12(3):137-139. PubMed 10539100

6. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook. Aurora, Colo: Esoterix−Colorado Coagulation; 2006.

7. Goodwin AJ, Rosendaal FR, Kottke-Marchant K, et al. A review of the technical, diagnostic, and epidemiologic considerations for protein S assays. Arch Pathol Lab Med. 2002 Nov; 126(11):1349-1366. PubMed 12421142

Aiach M, Borgel D, Gaussem P, Emmerich J, Alhenc-Gelas M, Gandrille S. Protein C and protein S deficiencies. Semin Hematol. 1997 Jul; 34(3):205-216 (review). PubMed 9241706

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.

Dahlback B. The protein C anticoagulant system: Inherited defects as basis for venous thrombosis. Thromb Res. 1995 Jan 1; 77(1):1-43. PubMed 7701473

Collection Details:

Patient Preparation:

Do not draw from an arm with a heparin lock or heparinized catheter.

Collection Instructions:

Blue-top (sodium citrate) tube.

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.