Heparin resistance in the intensive care unit

Abstract

Due to its complex pharmacokinetics, monitoring of unfractionated heparin (UFH) is required and is typically performed using either the activated partial thromboplastin time (APTT) or anti-factor Xa (anti-Xa) assay. In clinical practice, the term "heparin resistance" is commonly used when high doses of UFH fail to achieve the targeted therapeutic range. This arbitrary definition is inappropriate, particularly in critically ill patients, because it does not take into account patient weight, changes in heparin pharmacokinetics and/or pharmacodynamics, the clinical context, or factors affecting aPTT results. In most cases, the need to increase the dose of UFH administered to achieve the therapeutic range can be explained by interindividual variations in the pharmacokinetics and/or pharmacodynamics of the drug. The use of weight-adjusted nomograms, rather than arbitrary increases in heparin doses, allows rapid achievement of effective anticoagulation in most cases. In cases of acquired antithrombin deficiency <60%, the clinical benefit of administering antithrombin concentrates to optimize anticoagulation has not been clearly demonstrated. Data on the efficacy and safety of direct thrombin inhibitors remain insufficient to propose them as an alternative to heparin in critically ill patients outside of heparin induced thrombocytopenia.