Managing anticoagulant related coagulopathy

Abstract

There are several parenteral anticoagulants in use currently in the US. These include unfractionated heparin (UFH) commonly referred to as heparin, low-molecular weight heparins (LMWHs), synthetic pentasaccharide (fondaparinux), vitamin K antagonists (VKA) and direct thrombin inhibitors. The properties including mode of elimination, half-life, antidote and dose adjustment in renal failure of these drugs are listed in Table 1. VKA are the only orally approved anticoagulants with warfarin being the most commonly used in the United States with approximately three million users. This number of chronic warfarin users continues to increase annually as the baby boomers age and as patients over the age of 65 increase. It is estimated that approximately 26,000 major bleeding events occur annually in the United States. According to a recent study the incidence of anticoagulant associated intracerebral hemorrhage, the most feared and morbid bleeding complication, has quintupled in the US population in the 1990s [1]. The majority of this change can be explained by increasing warfarin use. A recent prospective study of 101 consecutive inpatients admitted to a tertiary care hospital in Boston [2] that looked at a cohort of patients with anticoagulation-associated hemorrhage suggested that excessive anticoagulation contributed independently to increased morbidity and mortality in hospitalized patients. The overall mortality at 60 days was 26% (13/50) in the excessive group compared with 10% (5/51) in the nonexcessive group (P = .03). Excessive warfarin therapy was associated with an increased 60-day mortality (P = .049), in contrast to excessive anticoagulation with UFH or LMWH alone (P = .27) or UFH or LMWH as a ‘‘bridge’’ to warfarin therapy (P = .10). Multivariate regression identified excessive anticoagulation as an independent predictor of 60-day mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 1.39–12.49; P = .01), along with intracranial hemorrhage (adjusted HR, 6.16; 95% CI, 1.75– 21.67; P = .005) and active cancer (adjusted HR, 3.79; 95% CI, 1.13–12.70; P = .03).