A partial factor V deficiency in anticoagulated lyophilized plasmas has been identified as a cause of the international normalized ratio discrepancy in the external quality assessment scheme.

Lyophilized normal and anticoagulated plasmas are increasingly used in External Quality Assessment schemes (EQAS) to assess the quality of performance of laboratories engaged in the control of oral anticoagulant therapy by means of the International Normalized Ratio (INR) system and for the standardization of the prothrombin time (PT). The main feature of the INR system is that the value measured for an individual plasma should be independent of the reagent used. This holds true only if the variable factors influencing the responsiveness of the reagents are the vitamin K-dependent clotting factors, the other factors being constant and within normal limits. We provide evidence that even a partial factor V (FV) deficiency (FV activity < 60 U/dl) in anticoagulated plasmas can be responsible for discrepancies between INR values as measured for a single lyophilized or fresh plasma by different reagents and that the discrepancy is proportional to and magnified by the International Sensitivity Index (ISI) of the reagent used. The greater the difference between ISI values, the wider the gap between INR values. Since FV is one of the most labile plasma clotting factors, its activity is likely to be lost during freeze-drying. Hence, we recommend a thorough control of the FV activity in commercial and home-made lyophilized plasmas before their use in EQAS and in the standardization of the PT.