The traceability of commercial plasma calibrators to the plasma International Standards for factor VIII and factor IX

Accurate measurement of coagulation factors is essential, especially for diagnosis of deficiency. Clinical laboratories use commercially available plasma calibrators, which should be traceable to the relevant plasma International Standard (IS). This study assessed the relationship between the plasma IS for factors IX (FIX) and VIII (FVIII) and some commonly used commercial calibrators. Calibrators from seven manufacturers were assayed for FIX and FVIII activity by one-stage clotting assay (OSCA) using different activated partial thromboplastin time (APTT) reagents and deficient plasmas, or chromogenic assay (CA). Results were calculated relative to the 4th IS Factors II,VII,IX,X, Plasma or the 6th IS Factor VIII/VWF, Plasma. Results for each calibrator were similar across the APTT reagents and deficient plasmas used. All calibrators showed a recovery of 90%-111% of the manufacturers' values, except calibrator C, which had recovery of around 85%. CA gave similar results, with good recovery for all but calibrator C. Similar low recoveries for OSCA and CA were found for a different lot of calibrator C and for a different calibrator product from manufacturer C. When all calibrators from manufacturer C were assayed by OSCA using the manufacturer's own deficient plasmas and APTT reagents, the mean recovery was still below 90%. Overall, there was good traceability of the international unit between the IS and commercial calibrator plasmas. Calibrators from one manufacturer consistently yielded lower than expected values for FIX and FVIII. This could lead to an over-estimation of the coagulation factor content in patient samples and demonstrates the importance of careful choice of calibrator.