Chapter 6: Anticoagulants

INTRODUCTION

Prevention and treatment of thrombus with anticoagulants have been primary goals of medicine for half a century. Previously known as antithrombotics, current guidelines recommend the term anticoagulants because of the multiple effects beyond thrombin inhibition. 1,2 Anticoagulants can be divided into indirect anticoagulants including unfractionated heparin (UFH), low- molecular-weight heparin (LMWH), heparinoids or synthetic heparins or direct anticoagulants including direct thrombin inhibitors (DTIs), and the oral vitamin K antagonist, warfarin.^1,2

Anticoagulation is a high-risk treatment with potentially adverse drug events resulting from the complexity of dosing, monitoring, and adherence^3,4,5 (Table 6-1). Anticoagulant-related medication errors and bleeding events with have been linked to an increased risk for stroke, myocardial infarction, and mortality.⁶ Based on one study, warfarin, along with insulin, was estimated to be responsible for one in every seven adverse drug events treated in emergency departments and more than 25% of all the estimated hospitalizations.⁷ An analysis of malpractice claims filed in the 1990s for a New England malpractice company revealed that anticoagulants were responsible for 8% of claims. Of these claims, 60% were considered preventable.⁸ Because of the increased potential for adverse events and concern for medication safety, The Joint Commission has implemented the safe use of anticoagulants as part of its 2008 National Patient Safety Goals.⁹

PARENTERAL ANTICOAGULANTS

Unfractionated Heparin

For indications requiring rapid anticoagulation, UFH has traditionally been the drug of choice for indications requiring rapid anticoagulation. It is a water-soluble heterogeneous mucopolysaccharide with complex effects on both the coagulation mechanism and blood vessels. UFH exerts its anticoagulant effect by interacting with antithrombin III, dramatically increasing its ability to bind and neutralize thrombin and other activated clotting factors. Given intravenously (IV), the onset of action is immediate. However, subcutaneous administrated heparin has a variable absorption, and the onset of action may be delayed.^2,10 The half-life of heparin is dose dependent, and anticoagulant effects range from 1 to 5 hours when given IV. UFH appears to be degraded and cleared primarily by the reticuloendothelial system, but a small amount of undegraded heparin is traceable in the urine. Its anticoagulant half-life may be prolonged in patients with renal insufficiency or hepatic cirrhosis and possibly shortened in patients with pulmonary embolism.^2,10 Occasionally, differences in the plasma concentrations of heparin-binding proteins may affect a patient's response to heparin. Because of significant variability and changes in patient ...