Recombinant and tissue extract thromboplastins for determination of international normalised ratio in over-anticoagulated patients

The international normalised ratio (INR)/international sensitivity index (I SI) system is established for calibration of thromboplastins for laboratory monitoring of oral anticoagulant therapy. The calibration procedure employ s patients stabilised on oral anticoagulants, and is therefore validated fo r patients within the therapeutic range. For practical reasons, the system is used for patients at all levels of therapy, including over-anticoagulate d patients with particularly low levels of factors II, VII and X. We studie d patients within and above the therapeutic range, using a thromboplastin c ontaining recombinant human tissue factor (Innovin) and two tissue extract thromboplastins. In samples with INRs from 2.0 to 4.0, there was good agree ment between results obtained with the three systems (mean INRs within 4% o f each other). In patients with INRs > 4.0, results with a human placental extract reagent (Thromborel S) were similar to those obtained with a rabbit brain thromboplastin (IL PT Fib I-Is Plus); mean INRs were 6.30 and 6.32 r espectively (not significant). Results with Innovin (mean INR: 7.67) were s ignificantly (P < 0.001) greater (on average by 22%) than those obtained wi th the other two materials. The discrepancy between results with different reagents negatively correlated with factor VII levels. Thus, the lower the factor VII level, the greater was the discrepancy between INRs. Unexpectedl y, there was a positive correlation between factor V level and the differen ce between INRs with different reagents. Thus, the higher the factor V leve l, the greater was the discrepancy between INRs. The effect of these differ ences at higher INRs on patient management is unknown, but the recently rev ised UK guidelines recommend that management of these patients should be in fluenced by clinical factors, reducing the relative importance of discrepan cies between results obtained with different systems.