Adding intravenous unfractionated heparin to standard enoxaparin causes excessive anticoagulation not detected by activated clotting time: Results of the STACK-on to ENOXaparin (STACKENOX) study

Abstract

The STACKENOX study assessed the cumulative anticoagulation effect of administering stack-on intravenous unfractionated heparin (UFH) to subjects already receiving enoxaparin. Seventy-two healthy subjects aged 40 to 60 years received subcutaneous enoxaparin (1 mg/kg every 12 hours) for 2.5 days (steady state) and were randomized to receive a 70 IU/kg intravenous UFH bolus 4, 6, or 10 hours after the final enoxaparin dose. Anticoagulation levels were assessed in subjects receiving enoxaparin alone and after the UFH bolus by monitoring activated clotting time (ACT), anti-Xa and anti-IIa activities, and thrombin generation (endogenous thrombin potential [ETP]). After the final enoxaparin dose, ETP levels decreased by 40%; anti-Xa and anti-IIa activities increased, as expected; and ACT levels did not indicate any anticoagulation effect. Stack-on UFH at 4, 6, or 10 hours after the last enoxaparin dose significantly increased anti-Xa and anti-IIa activities (P < .0001) to well above accepted therapeutic levels and resulted in total inhibition of thrombin generation for > or =2 hours; ACT levels remained within the range commonly observed in subjects receiving UFH. The administration of stack-on UFH to subjects already receiving recommended enoxaparin dosing may result in over-anticoagulation, and should be avoided. Activated clotting time assessment did not detect the over-anticoagulation resulting from co-administration of enoxaparin and UFH.