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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Caring for the Medically Ill: Improvements in the Management of Thromboembolic Disease


GOAL
To provide physicians with current information on the management of thromboembolic disease.

TARGET AUDIENCE
This activity is designed for cardiologists, orthopedic surgeons, general surgeons, emergency medicine practitioners, family practice physicians, internal medicine physicians, clinical pharmacists, and pharmacy services directors.

LEARNING OBJECTIVES
After reading this issue, the participant should be able to:

  • Discuss the clinical importance of venous thromboembolism in hospitalized patients with medical illness.
  • Summarize the results of trials addressing different approaches to thromboprophylaxis in hospitalized patients with medical illness.
  • Describe the design of ongoing clinical trials evaluating the role of prolonged thromboprophylaxis in hospitalized medical patients.
  • Analyze the data supporting the safety and efficacy of in-and outpatient treatment of deep vein thrombosis (DVT) with low-molecular-weight heparin-containing regimens.
  • Identify risk stratification for DVT among hospitalized medical and surgical patients.

ACCREDITATION STATEMENT
This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education. The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians. The Johns Hopkins School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this continuing medical education activity for a maximum of 1 hour in Category 1 credit toward the American Medical Association Physicians’ Recognition Award. Each physician should claim only those hours of credit that are actually spent on the educational activity. Credits are available until the expiration date of August 31, 2004.

This continuing education activity was produced under the supervision of Bruce Perler, MD, Professor of Surgery, Johns Hopkins University School of Medicine and Charles Locke, MD, Assistant Professor, Internal Medicine, Johns Hopkins University School of Medicine.

This program is approved for 1 hours of credit (0.1 CEUs) and is co-sponsored by The University of Tennessee College of Pharmacy who is approved by the American Council on Pharmaceutical Education as a provider of continuing pharmaceutical education. ACPE Program #064-999-02-238-H01.

This continuing pharmacy education activity was produced under the supervision of Glen E. Farr, PharmD, Associate Dean of Continuing Education, University of Tennessee College of Pharmacy.

This program is supported by an unrestricted educational grant from Aventis Pharmaceuticals.

Publisher's Note and Disclaimer: The opinions expressed in this issue are those of the authors, presenters, and/or panelists and are not attributable to the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or its Office of Continuing Medical Education. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this issue are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: www.galenpublishing.com. Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

CHAIRS

    Bruce Perler, MD
    Professor
    Department of Surgery
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Perler reports having no financial relationships with corporate organizations.

    Charles Locke, MD
    Assistant Professor
    Department of Internal Medicine
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Locke reports receiving honoraria from Aventis.

PARTICIPATING FACULTY

    Marc Cohen, MD, FACP
    Professor of Medicine
    Division of Cardiology
    MCP Hahnemann University School of Medicine
    Philadelphia, Pennsylvania
    • Dr Cohen reports receiving grant/research support from Aventis, Merck, Guidant, and COR; and serving as a consultant for DATAscope, Aventis and AstraZeneca.

    Russell D. Hull, MBBS, MSc, FRCPC, FACP, FCCP, FRACP
    Professor of Medicine
    Director, Thrombosis Research Unit
    University of Calgary
    Foothills Hospital
    Alberta, Canada
    • Dr Hull reports receiving grant/research support from, and serving as a consultant for Aventis, Pharmacia, DuPont, Emisphere and LEO Pharma.

    Geno J. Merli, MD, FACP
    Ludwig A. Kind Professor
    Director, Division of Internal Medicine
    Department of Medicine
    Jefferson Medical College
    Thomas Jefferson University
    Philadelphia, Pennsylvania
    • Dr Merli reports receiving grant/research support and honoraria from AstraZeneca and Aventis.

    Victor F. Tapson, MD, FACP
    Associate Professor of Medicine
    Division of Pulmonary and Critical Care Medicine
    Duke University Medical Center
    Durham, North Carolina
    • Dr Tapson reports serving as a consultant for Aventis.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Off Label Product Discussion
Faculty have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs and/or products: Enoxaparin (lovanox).

Deep vein thrombosis (DVT), pulmonary embolism (PE), and coronary artery disease are major causes of morbidity and mortality in the United States. This journal presents an overview of different approaches to thromboprophylaxis in hospitalized patients with medical illness, based on a national symposium held in Philadelphia, Pennsylvania, on April 12, 2002, as part of the annual meeting of the American College of Physicians and the American Society of Internal Medicine. Introductory remarks are offered by Victor F. Tapson, MD. The clinical importance of venous thromboembolism in hospitalized patients with medical illness is discussed by Russell D. Hull, MBBS, MSc. Geno J. Merli, MD, outlines the data supporting the safety and efficacy of inpatient and outpatient treatment of DVT with low-molecular-weight heparin. Marc Cohen, MD, describes appropriate antithrombotic regimens for the treatment of patients in acute coronary syndromes.

*Professor, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
†Assistant Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Introductory Remarks
Victor F. Tapson, MD*

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the United States, with as many as 2 million cases each year. Estimates suggest that approximately 200 000 to 600 000 cases of pulmonary embolism (PE) occur annually.1 VTE accounts for approximately 200 000 deaths every year.2 As many as 630 000 clinically significant VTEs occur in the United States annually—accounting for more deaths than breast cancer, AIDS, and highway fatalities combined.3 Thromboembolic disease is possibly the most common cause of unexpected death among hospitalized patients, and since it is difficult to detect and diagnose, it is also one of the top disease entities leading to medical malpractice litigation.

More than a century ago, Rudolph Virchow identified a triad of factors responsible for vascular thrombosis: vessel injury, stasis (immobility), and changes in the coagulability of the blood. Precipitating or anatomic factors for thromboembolism, such as surgery, trauma, hospitalization, or neurologic disease with paralysis are examples of the first 2 factors described by Virchow. The term "hypercoagulability" was designed to identify a syndrome of abnormalities of the third factor: coagulability of blood. Consequently, the traditional diagnosis of hypercoagulability was created for thromboembolism that occurred in the absence of precipitating or anatomic (noncoagulant) factors. Traditional hypercoagulability generally excluded patients who were 45 years or older or who had identifiable noncoagulant risk factors.4

However, today we know that many medical patients, even in the absence of defined precipitating factors, may also be at risk for thromboembolic disease. A classical medical patient at risk for deep vein thrombosis (DVT) and PE is illustrated by the case of a 60-year-old patient with congestive heart failure, whose baseline ejection fraction was approximately 35%, and who was hospitalized with pneumonia. Although the patient was prescribed bed rest, he did not receive DVT prophylaxis. Because the patient had limited mobility, on day 3 of hospitalization he underwent Foley catheterization and suddenly developed dyspnea and worsening hypoxemia. A ventilation/perfusion (VQ) scan was nondiagnostic, but a pulmonary arteriogram showed a massive PE. Clearly, this patient who had heart failure and was confined to bed rest offers a classic example of a medical patient at risk for DVT and PE—yet frequently such patients do not receive prophylactic treatment. Varying concepts as to what actually constitutes bed rest may be at issue. This patient was mobile a couple of times a day. Because his mobility was severely restricted, prophylaxis for DVT and PE would have been appropriate.

In this case, as in many medical cases, lack of prophylaxis is related to the subjective perceptions of the magnitude of the problem. Because VTE is most often clinically silent, the occurrence of overt VTE among an individual physician’s patients is perceived as rare.5 VTE generally is not the cause of hospitalization, but only becomes an issue subsequently—as occurred in the case of a 50-year-old male admitted to the hospital with chronic obstructive pulmonary disease. He was being treated with bronchodilators and steroids and appeared to be doing well. However, coronal and sagittal chest computed tomographic views showed clear evidence of PE that otherwise would likely have remained undiagnosed—a classic example of silent PE.

In an extensive review of DVT, PE prophylaxis and treatment guidelines, and clinical trial data, Geerts et al report that among 214 myocardial infarction patients, 25% of those who did not receive prophylaxis experienced DVT. Among 345 patients with ischemic stroke who were not treated prophylactically, 55% experienced DVT; among 528 medical patients, 16% experienced DVT.5 Such medical evidence overwhelmingly supports the need for prophylactic treatment. In fact, clinical evidence in support of prophylaxis was reported 20 years ago by Belch et al.6 In a randomized trial of 100 patients with congestive heart failure and/or chest infection, patients randomly received heparin 5000 U Q8h versus no prophylaxis, resulting in a reduction of DVT incidence from 26% to 4%. The authors reported that they "recommend prophylaxis with low-dose unfractionated heparin in patients with heart failure or chest infection who require more than three days of bed rest." Today many physicians believe that waiting 3 days is waiting too long.

Despite the magnitude of the incidence suggested by this study and that this knowledge has been circulated for 2 decades, awareness among internists of the risk of VTE in medical patients remains low. DVT FREE, an observational registry that will ultimately involve approximately 250 hospitals and 7500 patients, was initiated 2 years ago to prospectively track the epidemiology of DVT. Specifically, the registry will assess the clinical history of outpatients and inpatients with primary or secondary DVT diagnosed by ultrasound, with particular attention to risk factors, and ascertain what prophylaxis, if any, was administered prior to enrollment. Patients are admitted to the registry at the time of the ultrasound diagnosis of DVT. Consent is obtained, and patient charts are reviewed to collect background. Enrollment is now complete and this epidemiologic study promises to yield definitive information about DVT prevalence. Investigators are excited about analyzing study findings and, in particular, are interested in the spectrum of diseases and risk factors in study subjects. Also at question is whether medically ill patients are being undertreated with prophylaxis.

The need for ongoing study of DVT is evident, as the incidence of life-threatening PE is an understudied public health issue. Furthermore, the incidence, impact, and risk factors for VTE are underappreciated in the medical community. These realities have prompted the establishment of the American College of Chest Physicians (ACCP) Consensus Statement on Antithrombotic Therapy, which recommends that hospitals develop a formal strategy to address prevention of thromboembolic complications. The ACCP makes a grade 1A recommendation that general medical patients with risk factors for VTE (including cancer, bed rest, heart failure, severe lung disease) receive prophylactic treatment with unfractionated heparin or low-molecular-weight heparin therapy.5 The real tragedy is that many patients with pulmonary embolism do not survive long enough to receive treatment. A more systematic approach to prophylactic treatment for patients with VTE should be established.

REFERENCES

1. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation. 1996;93(12):2212-2245. Review.
2. Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis. 1975;17(4):259-270.
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population based perspective of the hospital incidence and case fatality rates of deep vein thrombosis and pulmonary embolism: The Worcester DVT Study. Arch Intern Med. 1991;151:933-938.
4. Abramson N, Abramson S. Hypercoagulability: clinical assessment and treatment. South Med J. 2001; 94(10):1013-1020.
5. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001;119(Suppl 1):132S-175S. Review.
6. Belch JJ, Lowe GD, Ward AG, et al. Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J. 1981;26:115-117.

*Associate Professor of Medicine in the Pulmonary and Critical Care Division at Duke University Medical Center in Durham, North Carolina.
Address correspondence to: Victor F. Tapson, MD, Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Bell Building, Durham, NC 27710.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.