Variation among Commercial Activated Partial Thromboplastin Time Reagents in Response to Heparin

Abstract

The activated partial thromboplastin time (APTT) has been advocated for monitoring heparin effect. This study was designed to determine the in vitro sensitivity to heparin of commercially available APTT reagents. Heparin was added in increasing concentrations to pooled citrated plasma. Fibrometer APTT determinations were performed at each concentration using General Diagnostics, Ortho, Dade, Hyland, and BBL reagents. A tilt-tube kaolin-activated partial thromboplastin time was also tested using a Sigma partial thromboplastin prepared by the method of Bell and Alton. The General Diagnostics, Sigma, and Ortho reagents displayed linear heparin sensitivity; the General Diagnostics APTT was prolonged 1 1/2-2 1/2 times in a plasma heparin range that prolonged a modified in-vitro Lee-White clotting times 2-3 times. The other reagents were either insensitive, too sensitive, or nonlinear in heparin response. Thus, commercial reagents vary widely in their in-vitro sensitivity to heparin.

The Prothrombinase-Induced Clotting Test: A New Technique for the Monitoring of Anticoagulants

“…These include non-linear dose-response relationships [1,2] as well as great variability among different instruments, reagents and even different batches of the same reagent [3][4][5]. In addition, the aPTT has a very low sensitivity towards LMWH and, with increasing doses of hirudin, a plateau effect occurs.…”

Heparin-containing block copolymers

“…The bioactivity of surface-immobilized heparin of heparin-containing block copolymers coated onto glass beads was analysed according to an APTT assay, modified to evaluate coated beads [17]. A standard curve was obtained as follows.…”

Heparinin VitroSensitivity of the Activated Partial Thromboplastin Time in Canine Plasma Depends on Reagent

“…1,12,14,20 However, different investigations in humans demonstrated remarkable differences in APTT reagents regarding their heparin sensitivity. 7,9,13,16,19 In dogs, the recommendations for the aspired APTT prolongation in human thrombosis therapy (1.5-to 2.5-times baseline) have been used without validation, 6,8 Figure 1. Activated partial thromboplastin time ratio (mean Ϯ SD, n ϭ 6) (APTT ratio ϭ actual APTT/mean APTT control) at different heparin activities measured after in vitro addition of heparin to normal canine plasma (reagent 1 ϭ Pathromtin, 2 ϭ PTT Reagent, 3 ϭ APTT Reagent, 4 ϭ APTT-FS Reagent, 5 ϭ Actin FS, 6 ϭ Dapttin, see Table 1).…”

“…15,17 Thus, it also became clear in humans that, in many laboratories, an APTT result that was 1.5-to 2.5-times the control is not equivalent to therapeutic heparin activities. 9,12,14,16 Consequently, it is recommended for humans that each laboratory should establish an individual therapeutic APTT ratio range for the heparin preparation used and for its own reagent and instrument system. 3,9,17 The APTT reagent and equipment used to measure APTT should be calibrated with heparin activities equivalent to the limits of the therapeutic range for thrombosis treatment in humans (0.3-0.7 IU/ml as determined by an antifactor Xa assay).…”