External quality assurance of antithrombin, protein C, and protein s assays: results of the College of American Pathologists proficiency testing program in thrombophilia

Arch Pathol Lab Med. 2011 Feb;135(2):227-32. doi: 10.5858/135.2.227.


Context: Hereditary and acquired deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are risk factors for venous thromboembolism. Proper diagnosis requires high-quality assays for these proteins.

Objective: To determine the accuracy and interlaboratory precision of AT, PC, and PS assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in thrombophilia and to grade the performance of laboratories.

Design: Standardized normal plasma with assigned analyte values was sent in 2 separate challenges to participating laboratories. Participants measured AT, PC, and PS levels using local methods.

Results: When compared with the assigned values for the international standard, the order of assay accuracy from highest to lowest was AT activity, PC antigen, AT antigen, total PS antigen, PC activity, PS activity, and free PS antigen (range of assay bias, 2.6%-8.8%). The order of assay precision from highest to lowest was PC activity, AT activity, AT antigen, total PS antigen, PS activity, free PS antigen, and PC antigen (range of assay coefficient of variation, 6.1%-20.0%). Most testing events (87.8%) could be graded as pass or fail using a target range of ±3 standard deviations from the method-specific mean. The pass rate was 98.2% for all AT, PC, and PS testing events combined.

Conclusions: Accuracy and precision were higher for AT assays and lower for PC and PS assays. It was feasible to grade individual laboratory performance.

MeSH terms

  • Antithrombins / blood*
  • Blood Chemical Analysis / methods*
  • Blood Chemical Analysis / standards*
  • Humans
  • Protein C / analysis*
  • Protein S / analysis*
  • Quality Assurance, Health Care*
  • Reproducibility of Results
  • Risk Factors
  • Thrombophilia / blood
  • Thrombophilia / diagnosis
  • United States


  • Antithrombins
  • Protein C
  • Protein S