0
Scientific Articles   |    
Thrombosis Prevention After Total Hip ArthroplastyA Prospective, Randomized Trial Comparing a Mobile Compression Device with Low-Molecular-Weight Heparin
Clifford W. Colwell, Jr., MD1; Mark I. Froimson, MD, MBA2; Michael A. Mont, MD3; Merrill A. Ritter, MD4; Robert T. Trousdale, MD5; Knute C. Buehler, MD6; Andrew Spitzer, MD7; Thomas K. Donaldson, MD8; Douglas E. Padgett, MD9
1 Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 11025 North Torrey Pines Road, Suite 140, La Jolla, CA 92037. E-mail address: colwell@scripps.edu
2 Orthopaedic and Rheumatologic Institute, Cleveland Clinic, 9500 Euclid Avenue, A-41, Cleveland, OH 44195
3 Center for Joint Preservation and Reconstruction, Rubin Institute, Sinai Hospital, 2401 West Belvedere Avenue, Baltimore, MD 21215
4 Joint Replacement Surgeons of Indiana Research Foundation, St. Francis Hospital, 1199 Hadley Road, Mooresville, IN 46158
5 Department of Orthopedic Surgery, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905
6 The Center, Orthopedic and Neurosurgical Care and Research, 2200 N.E. Neff Road, Suite 200, Bend, OR 97701
7 Kerlan Jobe Orthopaedic Clinic, 6801 Park Terrace, Los Angeles, CA 90045
8 Empire Orthopedic Specialty Clinic, 900 East Washington, Suite 200, Colton, CA 92324
9 Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Medical Compression Systems. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from commercial entities (Sanofi-aventis and Zimmer).

A commentary by Jay R. Lieberman, MD, is available at www.jbjs.org/commentary and as supplemental material to the online version of this article.
A video supplement to this article will be available from the Video Journal of Orthopaedics. A video clip will be available at the JBJS web site, www.jbjs.org. The Video Journal of Orthopaedics can be contacted at (805) 962-3410, web site: www.vjortho.com.

Copyright ©2010 American Society for Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2010 Mar 01;92(3):527-535. doi: 10.2106/JBJS.I.00047
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case

Abstract

Background: 

Thromboembolic disease is a common complication of total hip arthroplasty. The purpose of this study was to compare a new mobile compression device with low-molecular-weight heparin with regard to their safety and effectiveness for the prevention of venous thromboembolic disease.

Methods: 

Patients who had a total hip arthroplasty were randomized to receive prophylaxis with a mobile compression device or low-molecular-weight heparin for ten days. Use of the compression device began intraoperatively, and the patients in this group could receive 81 mg of aspirin daily after the surgery. The first injection of the low-molecular-weight heparin began between twelve and twenty-four hours after the surgery. After ten to twelve days, all patients underwent bilateral lower-extremity duplex ultrasonography to screen for deep venous thrombi in the calf and thigh. Any clinical symptoms of pulmonary embolism were evaluated with spiral computed tomography lung scans. Bleeding events and utilization of (i.e., compliance with) prophylactic treatment in both groups were documented. Clinical evaluation to look for evidence of deep venous thrombi and pulmonary emboli was performed at twelve weeks postoperatively.

Results: 

Four hundred and ten patients (414 hips) were randomized; 392 of these patients (395 of the hips) were evaluable with regard to the safety of the intervention and 386 patients (389 hips) were evaluable with regard to its efficacy. Demographics were similar clinically between the groups. The rate of major bleeding events was 0% in the compression group and 6% in the low-molecular-weight heparin group. The rates of distal and proximal deep venous thrombosis were 3% and 2%, respectively, in the compression group compared with 3% and 1% in the heparin group. The rates of pulmonary embolism were 1% in the compression group and 1% in the heparin group, and there were no fatal pulmonary emboli. Within the twelve-week follow-up period, two events (one deep venous thrombosis and one pulmonary embolus) occurred in one patient in the compression group following negative findings on duplex ultrasonography on the twelfth postoperative day. There was no difference between the groups with regard to the prevalence of venous thromboembolism.

Conclusions: 

When compared with low-molecular-weight heparin, use of the mobile compression device for prophylaxis against venous thromboembolic events following total hip arthroplasty resulted in a significant decrease in major bleeding events.

Level of Evidence: 

Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Figures in this Article
    Sign In to Your Personal ProfileSign In To Access Full Content
    Not a Subscriber?
    Get online access for 30 days for $35
    New to JBJS?
    Sign up for a full subscription to both the print and online editions
    Register for a FREE limited account to get full access to all CME activities, to comment on public articles, or to sign up for alerts.
    Register for a FREE limited account to get full access to all CME activities
    Have a subscription to the print edition?
    Current subscribers to The Journal of Bone & Joint Surgery in either the print or quarterly DVD formats receive free online access to JBJS.org.
    Forgot your password?
    Enter your username and email address. We'll send you a reminder to the email address on record.

     
    Forgot your username or need assistance? Please contact customer service at subs@jbjs.org. If your access is provided
    by your institution, please contact you librarian or administrator for username and password information. Institutional
    administrators, to reset your institution's master username or password, please contact subs@jbjs.org

    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
    CME Activities Associated with This Article
    Submit a Comment
    Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
    Comments are moderated and will appear on the site at the discretion of JBJS editorial staff.

    * = Required Field
    (if multiple authors, separate names by comma)
    Example: John Doe





    Clifford W. Colwell Jr., MD
    Posted on July 14, 2010
    Dr. Colwell responds to Drs. Bottaro and Ceresetto
    Shiley Center for Orthopaedic Research & Education at Scripps Clinic, La Jolla, California

    We appreciate the very thoughtful letter submitted to the JBJS with reference to our article. Dr. Bottaro has appropriately noted that the definitions of major and minor bleeding in prophylaxis protocols have differed widely depending upon the study. We agree this is true and has been so stated in the literature (1,2). This was the basis of our decision to use a direct comparator rather than use bleeding rates from previous studies with varying criteria. We set the criteria for major and minor bleeding based on participating surgeons’ concerns before the initiation of the study and both cohorts were judged by the same criteria. The fact that the study was randomized and prospective did not allow any of the investigators to choose a specific patient for one cohort or the other. The numbers of patients who fell into the major or minor bleeding categories were then tabulated; the data analyzed and reported in Table II. Adjudication occurred for every major and minor bleed for accuracy. Those patients who did not have a major or minor bleeding event were not adjudicated. To question our definition of major bleeding is reasonable, as it is reasonable to question the definitions of major and minor bleeding in previous studies. As in those studies, you can only evaluate the results and quality of the individual study on how you think bleeding should be defined. Orthopaedic surgeons worldwide have accepted an increased bleeding rate when utilizing pharmacologic protocols to obtain better efficacy, i.e., lower deep vein thrombosis and pulmonary embolism rates. Our study demonstrates that a modality is now available to significantly decrease these defined rates of major bleeding with no apparent difference in efficacy. A new study is underway to document either superiority or noninferiority with respect to efficacy using this methodology. We appreciate the letter and our opportunity to respond.

    References

    1. Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202-4.

    2. Dahl OE, Bergqvist D. Current controversies in deep vein thrombosis prophylaxis after orthopaedic surgery. Curr Opin Pulm Med. 2002;8:394-7.

    Federico J. Bottaro, MD
    Posted on June 10, 2010
    How Should We Define Major Bleeding Events in Thromboprophylaxis?
    Hospital Británico de Buenos Aires, Buenos Aires, Argentina

    To the Editor:

    Major bleeding is the most important safety endpoint in studies on drugs affecting haemostasis for deep venous thrombosis (DVT) prophylaxis but an adequate definition of major bleeding in surgical studies is still an issue of debate (1). Colwell et al. (2) reported that, compared with low-molecular-weight heparin (LMWH), the use of a mobile compression device for DVT prophylaxis following total hip arthroplasty (THA) resulted in a significant decrease in major bleeding events. However, this conclusion may be misleading. The definition of major bleeding in this study included bleeding that required re-hospitalization or prolonged hospitalization, required any intervention such as surgery or hematoma aspiration to prevent permanent impairment or damage, endangered critical organs (intracerebral, intraocular, intraspinal, pericardial, or retroperitoneal), was life threatening, or caused death. Eleven episodes of major bleeding were adjudicated to the enoxaparin group; however, the qualifying criterion of major bleeding in 6 of these patients was prolonged hospitalization and in 3 was re-hospitalization, but none of these patients required any intervention. No major bleeding events were adjudicated to the compression device group. This difference in the rate of major bleeding was inconsistent with the reported total number of blood units used, number of transfusions, mean number of units transfused per group, mean number of units transfused per patient, mean bleeding index, number of patients with a bleeding index of ≥2, number of patients with a change of ≥20 g/L, and mean change in hemoglobin. No episodes of bleeding that endangered critical organs, was life threatening, or caused death were seen in both groups. It is also interesting to note that, although most studies with an increase in the rate of major bleeding also show an increase in the rate of minor bleeding, in the present study the rate of minor bleeding was similar in both groups (37% and 42% in the compression device and enoxaparin group respectively, p=0.319). The authors also reported that the rate of major bleeding found in the enoxaparin group is similar to the 5.3% rate reported after the pooling of the results of five studies which utilized LMWH after THA (3). However, these five studies used different definitions of major bleeding and were done in the '90s. Recent pooled analysis of studies of THA with new oral antithrombotic drugs that used enoxaparin as comparator, central adjudication committees and objective criteria of major bleeding, showed major bleeding rates of less than 1.5% (4,5). Moreover, previous studies comparing mechanical compression devices versus enoxaparin in hip replacement found no significant differences in the rate of major bleeding (6,7). Furthermore, the reported rate of major bleeding in the placebo group in previous studies versus enoxaparin after THA was 4%, showing that patients who did not receive any antithrombotic drug also can bleed due to the surgical procedure itself (8,9). We believe that the elevated rate of major bleeding reported by Colwell et al. in the enoxaparin group is overestimated and could be due to the open label nature of the study, the absence of an independent, blinded, adjudication committee and the use of subjective qualifying criterion to define major bleeding.

    The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

    References

    1. Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202-4.

    2. Colwell CW Jr, Froimson MI, Mont MA, Ritter MA, Trousdale RT, Buehler KC, Spitzer A, Donaldson TK, Padgett DE. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92:527-35.

    3. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW; American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):381S-453S.

    4. Friedman RJ, Dahl OE, Rosencher N, Caprini JA, Kurth AA, Francis CW, Clemens A, Hantel S, Schnee JM, Eriksson BI; for the RE-MOBILIZE, RE-MODEL, RE-NOVATE Steering Committees. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb Res. 2010 May 14. [Epub ahead of print]

    5. Clayton RA, Gaston P, Howie CR. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br. 2010;92:468.

    6. Warwick D, Harrison J, Glew D, Mitchelmore A, Peters TJ, Donovan J. Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial. J Bone Joint Surg Am. 1998;80:1158-66.

    7. Pitto RP, Hamer H, Heiss-Dunlop W, Kuehle J. Mechanical prophylaxis of deep-vein thrombosis after total hip replacement a randomised clinical trial. J Bone Joint Surg Br. 2004;86:639-42.

    8. Turpie AG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, Andrew M, Hull RD, Gent M. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315:925-9.

    9. Colwell CW Jr, Spiro TE. Efficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty. Clin Orthop Relat Res. 1995;319:215-22.

    Clifford W. Colwell Jr., MD
    Posted on April 23, 2010
    Dr. Colwell responds to Mr. Rogers
    Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, California

    We appreciate the interest in our article and the questions posed by Mr. Rogers. The duplex ultrasound was used as a screening test at 10 to 12 days following surgery and, if the test was negative, prophylaxis was discontinued. We followed all patients for three months postoperatively, for clinical signs and symptoms of deep venous thrombosis or pulmonary embolism. We had only one patient who had a negative duplex ultrasound study who subsequently developed an event within the three-month window, in this case a deep venous thrombosis and pulmonary embolism. This patient was in the external device arm of the study. We did not perform duplex ultrasound studies or spiral computer tomography on patients who were asymptomatic at three months. All of the patients positive for deep venous thrombosis or pulmonary embolism developed these complications within the 10 to 12 day postoperative period and were diagnosed either prior to or at the time of the screening duplex ultrasound study. None of the patients in the Planes study had a duplex screening test and therefore we do not know whether they would have had a change in their outcomes with the test.

    Based on this study, we are very comfortable using a ten-day external device prophylaxis protocol and have changed our practice to reflect this confidence. The study was not powered to address the issue of whether a 10 to 12 day postoperative duplex ultrasound study is necessary as a screening examination. Although I see no harm in carrying out the protocol for 21 days, I have no data to support this time frame.

    As you have noted, the number of cases of heparin-induced thrombocytopenia in the short-term prophylaxis in the orthopaedic protocols is extremely rare and is addressed in the literature as case reports only. All of our patients in this study or on low-molecular-weight heparin routinely undergo serial platelet counts (averaging three) during their hospitalization. We stop the low-molecular-weight heparin if the platelet count drops below 100,000. We did not carry out qualitative platelet studies and, in fifteen years of low-molecular-weight heparin use averaging over one thousand hip and knee replacements per year, we have not seen a single case of heparin-induced thrombocytopenia.

    Benedict A. Rogers, MA, MSc, MRCGP, FRCS(Orth)
    Posted on March 22, 2010
    Venous Thromboembolic Prophylaxis After Hip Replacement
    South West Thames, United Kingdom

    To the Editor:

    I read with interest the March 2010 article by Colwell et al. (1) entitled, “Thrombosis Prevention After Total Hip Arthroplasty...” and would like to make the following points.

    The Methods section states not only that, “Treatment was continued for 10 days” but also that duplex ultrasonography was performed on both groups at 10-12 days after surgery. However, the published data of the Global Orthopaedic Registry, collating data from over 13,000 patients from 13 countries, has demonstrated that the peak incidence of venous thromboembolism occurs at a mean of 21 days after surgery (2). Further, the conclusions by Planes et al. (3), cited in this paper, state that, “the risk of late-occurring DVT remains high at least until day 35 after surgery”.

    In view of the results from Planes et al. and the Global Orthopaedic Registry, do the authors feel that 10-12 days of treatment as advocated in this study, either pharmaceutical or non-pharmaceutical, is sufficient to effective prophylaxis against venous thromboembolism? In addition, do the authors consider the conclusions drawn by this study valid at 21 or more days following surgery and if so what evidence exists to justify this extrapolation?

    Case reports published in this journal have highlighted some serious complications of low molecular weight heparin (LMWH) use, notably heparin-induced thrombocytopenia (4,5). Since this is a potentially fatal complication, can the authors confirm that the patients receiving LMWH in this study had regular platelet count monitoring, as recommended (6), to screen for heparin-induced thrombocytopenia?

    The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

    References

    1. Colwell CW Jr, Froimson MI, Mont MA, Ritter MA, Trousdale RT, Buehler KC, Spitzer A, Donaldson TK, Padgett DE. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92:527-35.

    2. Warwick D, Friedman RJ, Agnelli G, Gil-Garay E, Johnson K, FitzGerald G, Turibio FM. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br. 2007;89:799-807.

    3. Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet. 1996;348:224-8.

    4. Barber FA, Burton WC, Guyer R. The heparin-induced thrombocytopenia and thrombosis syndrome. Report of a case. J Bone Joint Surg Am. 1987;69:935-7.

    5. Lilikakis AK, Papapolychroniou T, Macheras G, Michelinakis E. Thrombocytopenia and intra-cerebral complications associated with low-molecular-weight heparin treatment in patients undergoing total hip replacement. A report of two cases. J Bone Joint Surg Am. 2006;88:634-8.

    6. Boshkov LK, Warkentin TE, Hayward CP, Andrew M, Kelton JG. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol. 1993;84:322-8.

    Related Content
    The Journal of Bone & Joint Surgery
    JBJS Case Connector
    Topic Collections
    Hip
    Related Audio and Videos
    PubMed Articles
    Guidelines
    Antithrombotic therapy supplement. -Institute for Clinical Systems Improvement
    Results provided by:
    PubMed
    Clinical Trials
    Readers of This Also Read...
    JBJS Jobs
    01/08/2014
    Pennsylvania - Penn State Milton S. Hershey Medical Center
    11/15/2013
    Louisiana - Ochsner Health System
    01/22/2014
    Pennsylvania - Penn State Milton S. Hershey Medical Center