Monitoring heparin anticoagulation in the acute phase response

Abstract

The anticoagulant effect of unfractionated heparin (UFH) is monitored using the activated partial thromboplastin time (APTT). An APTT of 1.5-2.5 times the control is usually taken as the therapeutic range and assumed to reflect an anti-activated factor X (anti-Xa) level of 0.35-0.7 u/ml. However, in some cases, despite administration of sufficient heparin to achieve a therapeutic anti-Xa assay level, the APTT remains sub-therapeutic. This 'apparent heparin resistance' is commonly due to high levels of factor VIII (FVIII). In these situations, the anti-Xa is usually preferred for monitoring in order to avoid, what might be, dangerously high levels of heparin. We hypothesized that at high FVIII levels, the heparin resistance encountered may be genuine rather than apparent and that higher doses of heparin may indeed be needed for an equivalent anticoagulant effect. The relationship between heparin level, APTT and anticoagulant effect at different FVIII concentrations was determined using thrombelastography and the thrombin generation assay. Thromboelastographic and thrombin generation parameters concurred with APTT, demonstrating a genuine heparin resistance in the presence of high FVIII levels. This suggests that APTT may be a more accurate measure of anticoagulant effect in vivo than anti-Xa.