Critical Care Express Report

Based on Data Presented at a Satellite Symposium during the 35^th Critical Care Congress of the Society of Critical Care Medicine, January 8, 2006, San Francisco, California

Publication date: 2006-02-30

Deep Vein Thrombosis and Heparin-induced Thrombocytopenia: Optimal Treatment in the Critically Ill Patient

This report was reviewed for medical and scientific accuracy by Robert Eisenstein, MD, Vice Chairman, Department of Emergency Medicine, University of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Expert Commentary

Provided by Stanley A. Nasraway, Jr., MD, FCCM, Associate Professor of Surgery, Medicine, and Anesthesia, Tufts University School of Medicine; Director, Surgical Intensive Care Units, New England Medical Center; Boston, Massachusetts.

The management of thromboembolic disorders in the critical care setting poses a significant challenge for emergency, critical care, and intensivist physicians. Early recognition, prompt, accurate diagnosis and aggressive treatment are essential in avoiding potential short- and long-term sequelae associated with these disorders.

Venous thromboembolism, whether manifested as deep vein thrombosis or pulmonary embolism, is a common risk factor for patients undergoing major surgeries (eg, abdominal, orthopedic) or cardiac procedures (eg, percutaneous coronary intervention [PCI]). Conventional treatment options for the prophylaxis and treatment of venous thrombo-embolism include unfractionated heparin, low-molecular-weight heparins, and vitamin K antagonists (eg, warfarin). Even with prophylaxis or treatment with unfractionated heparin or low-molecular-weight heparins, venous thromboembolism remains the cause of significant morbidity and mortality. Moreover, the use of these agents, in and of themselves, can pose a risk for the development of heparin-induced thrombocytopenia (HIT), a devastating complication that occurs in up to 5% of heparin-treated patients.^1–4 HIT remains an under-recognized complication of modern intensive care medicine with serious consequences. Outcomes associated with the development of HIT can include venous or arterial thrombosis, amputation and death.⁴ Approximately 50% of patients with HIT develop a thromboembolic event,⁵ of which approximately 20% will require amputation and 30% will die.⁶ Understanding the onset and time course of HIT, with immediate discontinuation of the causative agent and initiation of direct thrombin inhibitor therapy (eg, argatroban or lepirudin), may be critical. With constant vigilance, sound clinical judgment, and appropriate therapeutic intervention, this potentially lethal condition can be managed and its complications averted.

In recent years, significant progress has been made in the treatment and prophylaxis of venous thromboembolism. Newer anticoagulant agents offer potential advantages over conventional anticoagulant therapies with improved pharmacologic and clinical profiles.⁷ One of these agents, fondaparinux, is the first in a new class of synthetic penta-saccharide anticoagulants that binds selectively to antithrombin and directly inhibits the action of factor Xa.⁸ Clinical trials have demonstrated fondaparinux was at least comparable to unfractionated heparin for the initial treatment of pulmonary embolism and to low-molecular-weight heparin for the initial treatment of deep vein thrombosis.^9,10 The pharmacokinetic profile of fondaparinux is characterized by a high bioavailability following subcutaneous administration, slow elimination (allowing once-daily administration), and dose-dependent clearance.¹¹ The predictable and more reliable anticoagulant response of fondaparinux obviates the need for laboratory monitoring. Moreover, the limited binding to platelet factor 4 (PF4) suggests that fondaparinux will not cause HIT.¹²

This Critical Care Express Report^TM reviews data on the diagnosis, prevention and treatment of thromboembolic disorders presented at a satellite symposium held during the 35^th Critical Care Congress of the Society of Critical Care Medicine.

Venous Thromboembolism

Venous thromboembolism is a significant problem in hospitalized patients. Approximately 2 million patients a