THROMBOSIS EXPRESS REPORT™

Based on Data Presented at a Satellite Symposium during the 40th American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting and Exhibition, December 6, 2005, Las Vegas, Nevada

Publication date: 2006-1-31

Thromboembolic Disorders: Management Strategies to Optimize Outcomes

This report was reviewed for medical and scientific accuracy by Linda M. Spooner, PharmD, BCPS, Clinical Pharmacy Specialist in Infectious Diseases, Jersey Shore University Medical Center, Neptune, New Jersey; Clinical Assistant Professor, Ernest Mario School of Pharmacy, Piscataway, New Jersey

Introduction

In recent years, significant progress has been made in the treatment and prophylaxis of thromboembolic disorders. The addition of new anticoagulant agents and continually expanding clinical uses has vastly expanded the anticoagulant armamentarium. Newer anticoagulant agents may offer significant advantages over traditional anticoagulant therapies with improved pharmacologic and clinical profiles. ¹ As serious short- and long-term sequelae can result from the inappropriate management of thromboembolic disorders, early recognition, diagnosis and aggressive treatment are essential for successful outcomes.

Venous thromboembolism (VTE) is the cause of significant morbidity and mortality, with over 200,000 new cases of VTE diagnosed annually in the United States. ² Of these, 30% will die within 3 days, 20% will suffer sudden death due to pulmonary embolism, and approximately 30% will develop recurrent VTE within 10 years. ² Standard treatment options for VTE include unfractionated heparin, low-molecular-weight heparins, and warfarin. However, these agents have several limitations, such as frequent laboratory monitoring and variable dosage requirements. ¹ Moreover, adverse events such as heparin-induced thrombocytopenia (HIT) are a concern with unfractionated heparin and to a lesser extent with low-molecular-weight heparins. These limitations have led to the development of newer antithrombotic agents, such as factor Xa inhibitors (eg, fondaparinux [Arixtra]). These agents exhibit a targeted mechanism of action, more predictable pharmacodynamics and pharmacokinetics, fixed and simpler dosing regimens, and few or no laboratory monitoring requirements.

HIT is an immune-mediated adverse drug reaction of heparin therapy. ³ HIT occurs in approximately 1-5% of patients receiving unfractionated heparin (approximately 300,000 patients per year). ^4,5 It is estimated that up to 50% of patients with isolated HIT will develop a thromboembolic event, ⁶ of which approximately 20% will require amputation and 30% will die. ⁷ Serious thromboembolic complications include deep vein thrombosis, pulmonary embolism, myocardial infarction, occlusion of limb arteries, skin necrosis, cerebrovascular accident, end organ damage, or death. ^6,8 Despite serious clinical consequences, HIT remains an under-recognized and under-diagnosed condition. Effective treatment of HIT includes immediate withdrawal of heparin (or low-molecular-weight heparin) and initiation of a direct thrombin inhibitor (eg, argatroban, lepirudin, bivalirudin). ^9-11 Bivalirudin is limited to the treatment of patients with or at risk for HIT who are undergoing percutaneous coronary intervention. ¹²

This Thrombosis Express Report^TM reviews data presented at a satellite symposium held during 40^th American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting and Exhibition that focused on current perspectives for the optimal management of VTE and HIT.

Venous Thromboembolism -Focus on Factor Xa Inhibition

VTE (deep vein thrombosis, pulmonary embolism) is a major public health concern with serious long-term consequences, according to Edith A. Nutescu, PharmD, Clinical Associate Professor, The University of Illinois at Chicago, College of Pharmacy & Medical Center, Chicago, Illinois. ¹³ Approximately 30% of patients will develop recurrent deep vein thrombosis and 30% will develop post-thrombotic syndrome up to 8 years after an initial episode of VTE. ¹⁴ Furthermore, the survival rate diminishes significantly with recurrence, from 80% at 2 years to 69% at 8 years. ¹