Monitoring heparin anticoagulation in the acute phase response

Abstract

Summary 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.

Apparent Argatroban Resistance in a Patient with Elevated Factor VIII Levels

“…Apparent heparin resistance is an inadequate aPTT response in vitro despite appropriate in vivo antithrombotic efficacy of heparin as measured by anti-Xa levels. 4 To our knowledge, this is the first report of apparent argatroban resistance associated with elevated factor VIII levels. A recent report described a patient who received argatroban doses up to 15.5 µg/kg/min to achieve the desired aPTT.…”

Controversies in heparin monitoring

“…For example, a patient with factor XII deficiency may have a prolonged aPTT, however will not have an increased risk of bleeding, whereas a patient with factor VIII deficiency and a similarly prolonged aPTT will have a high risk of bleeding. Patients with acute inflammatory states may also manifest heparin resistance [14, 22, 23].…”

New anticoagulants: how to deal with treatment failure and bleeding complications

“…On the other hand, using thromboelastography and thrombin generation, Uprichard et al . have recently shown that aPTT may be a more accurate measure of anticoagulant effect of UFH in vivo than anti‐Xa assay [13]. Whereas monitoring of LMWHs is not required routinely, anti‐Xa assay, rather than aPTT, may be useful for optimizing dose in certain groups of patients such as the elderly, pregnant and in renal failure [14].…”