Alexander KP et al. (2005) Excess dosing of antiplatelet and antithrombin agents in the treatment of non–ST-segment elevation acute coronary syndromes. JAMA 294: 3108–3116

Given concern about bleeding risk with use of antithrombotic therapy, Alexander et al. investigated whether unintentional excess dosing of adjustable anticoagulants, specifically unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or glycoprotein IIb/IIIa inhibitors, affects outcomes of patients with non-ST-segment elevation acute coronary syndromes.

This prospective analysis included 30,136 patients. Excess doses were received by 42% of patients who were given at least one antithrombotic agent. Factors associated with excess dosing included age ≥75 years, female sex, renal insufficiency and treatment at a hospital with a history of low adherence to guidelines. Patients receiving excess doses of LMWH or glycoprotein IIb/IIIa inhibitors were considerably more likely to experience major bleeding than those receiving recommended doses (adjusted odds ratios 1.39 and 1.36, respectively); a slight trend towards increased bleeding in patients receiving excess UFH was also seen (odds ratio 1.08). Most excess dosages were minor, but 9.9% of patients receiving UFH, 3.1% receiving LMWH and 2.1% receiving a glycoprotein IIb/IIIa inhibitor received a major excess dose. For all treatments, major bleeding episodes increased in relation to the degree of excess, but even minor excesses were associated with harm, suggesting that safety concerns persist with any degree of excess. Only excess glycoprotein IIb/IIIa inhibitor dosing was associated with increased risk of death, but excess dosing of any of the treatments was associated with longer hospital stay.

Despite use of the correct medications, dosing errors increased the risk of bleeding in already vulnerable patients. The authors urge that doses are calculated carefully, to reduce bleeding risk in these patients.