2023-09-03-世界卫生组织-WHO_BS_2023.2457_WHO_1st_International_Standard_TAFI,_Plasma_41页_837kb

• Objective: The collaborative study aimed to establish an international reference standard for measuring TAFI (Thrombin Activatable Fibrinolysis Inhibitor) activity and antigen in plasma, avoiding inter-laboratory variability.

• Key Activities:

  • 10 laboratories from 7 countries measured TAFI activity and/or antigen using ampoules A (candidate standard), normal control B, low-TAFI control C, and high-TAFI control D.
  • Assays were bioanalyzed using statistical methods (Combistats software), yielding potency values relative to local standards, pooled plasma, or international units (IU).
  • Independent quantification used isotope-dilution mass spectrometry (IDMS) to determine TAFI antigen in SI units (µg).

• Proposed WHO 1st International Standard: Product code 17/200 (Sample A), assigned:

  • TAFI:Activity: 0.87 IU per ampoule.
  • TAFI:Antigen: 0.92 IU per ampoule.
  • TAFI:Antigen (SI units): 7.43 µg per ampoule (expanded uncertainty with k=2 corresponds to 95% confidence).

• Validation/Supporting Findings:

  • Consistent results across 5,349 analyses from 12 months’ accelerated thermal stability testing.
  • Short-term bench stability after reconstitution confirmed losses of ≤4.5% over 6 hours.
  • Reproducibility showed low inter-laboratory variability (GCV ≤5.06%), increasing confidence in the standard.
  • IDMS values for Sample A showed low variability (CV=4.5%), affirming its suitability as an SI-unit reference.

• Recommendations:

  • Studies should complete potency assays within 4 hours after standard reconstitution.
  • IDMS should be implemented for harmonizing TAFI antigen quantification globally.

Summary [WHO/BS/2023.2457]

This study successfully calibrated a WHO 1st International Standard (Sample A, code 17/200) for TAFI plasma. Key findings include:

• Establishment of standardized TAFI potency values (activity: 0.87 IU/ampoule; antigen: 0.92 IU/ampoule; antigen: 7.43 µg/ampoule) with high robustness.
• Stability results (thermal degradation and bench stability) support use for harmonizing TAFI measurements across laboratories.
• IDMS verification aligns with the assigned SI-unit value.