A comparison of the sensitivity of APTT reagents to the effects of enoxaparin, a low-molecular weight heparin.

Low-molecular weight heparin (LMWH) is the product of enzymatic or chemical degradation of unfractionated heparin (UFH). It has been found to have better bio-availibility, more predictable dose response and can be used as an alternative to UFH for prophylaxis and treatment of thrombotic disorders. It is claimed that no laboratory monitoring is necessary for LMWH therapy; however, for the aged, renal impaired, obese or grossly underweight, monitoring of dose effect with anti-Xa assay is recommended. The activated partial thromboplastin time (APTT), which is the test of choice for UFH monitoring, is believed to be insensitive to the effect of LMWH. The sensitivity of the APTT to heparin lies in the APTT reagent used. In this study, eight different APTT reagents were used to compare the APTT with anti-Xa activity in ex vivo plasma from patients who were on enoxaparin (LMWH, Clexane) therapy. It was found that, as with UFH, APTT reagents show variable sensitivity to LMWH. The APTTs from all eight reagents were found to have a linear relationship to anti-Xa activity. The APTT results using three of the reagents gave an indication of the use of LMWH therapy. It was also found that patients who were lupus anticoagulant (LA)-positive had much more prolonged APTTs when on LMWH therapy; however, a linear correlation between APTT and anti-Xa was not present in these patients.

Comparison of thromboplastins using the ISI and INR system.

Twelve thromboplastins were tested against a secondary reference thromboplastin (human brain CRM BCR No. 147) or a tertiary house standard (human brain thromboplastin) with plasmas from normal healthy individuals and patients on oral anticoagulant therapy. The relationship between the prothrombin ratios of the thromboplastins tested versus the reference reagent was either a straight or curved line. The International Sensitivity Index (ISI) was estimated for each of the test thromboplastins and these ranged from 0.98 to 2.24. Some ISIs stated by manufacturers were different from our results. Thromboplastins with a high ISI showed a loss of sensitivity in assessing the level of anticoagulation at the upper end of the therapeutic range. In addition, the 95% Confidence Interval (CI) of the ISI estimations were widest for thromboplastins with the highest ISIs. Conversion of the prothrombin ratio to International Normalized Ratio (INR) was most accurate with the Australasian Reference Thromboplastin (ART) and least accurate with reagents having an ISI of 2.00 and over. Thromboplastins with an ISI between 1.10 and 1.50 may be adequate for the control of oral anticoagulant therapy, but were less accurate than a thromboplastin with an ISI approximating 1.00. Factors other than ISI should be considered in the choice of a thromboplastin, in particular a measurement of the accuracy of the ISI estimation such as the 95% confidence interval estimation used here.