Annals
Established in 1927 by the American College of Physicians
:
Advanced search
box Article
 arrow  Table of Contents                
space
 arrow  PDF of this article
space
 arrow  Figures/Tables List
space
 arrow  Related articles in Annals
space
box Services
 arrow  Send comment/rapid response letter
space
 arrow  Notify a friend about this article
space
 arrow  Alert me when this article is cited
space
 arrow  Add to Personal Archive
space
 arrow  Download to Citation Manager
space
 arrow  ACP Search
space
 arrow  Get Permissions
space
box Google Scholar
 arrow  Search for Related Content
space
box Social Bookmarking
 Add to CiteULike Add to Complore Add to Connotea Add to Del.icio.us Add to Digg Add to Facebook Add to Reddit Add to Technorati Add to Twitter
What's this?
box PubMed
Articles in PubMed by Author:
 arrow  Camporese, G.
space
 arrow  Bernardi, E.
space
 arrow  PubMed                     
space

REPLY

Is Low-Molecular-Weight Heparin Suitable in All Patients Undergoing Knee Arthroplasty?

right arrow Giuseppe Camporese, MD; Franco Noventa, MD; and Enrico Bernardi, MD, PhD

4 November 2008 | Volume 149 Issue 9 | Pages 687-688


IN RESPONSE:

We appreciate Dr. Geerts' evaluation of our work. We are aware that our conclusions differ from the 8th ACCP guidelines about the prevention of VTE after knee arthroscopy (1). We also note that Table 9 in those guidelines incorrectly lists the incidence of VTE found in our trial: The table's numbers for our trial differ from those presented at the last International Society of Thrombosis and Haemostasis Congress and from those presented in our article. We offer the following responses to the other points made by Dr. Geerts.

First, we agree that the accuracy of ultrasonography in the setting of asymptomatic calf DVT is suboptimal (2). As stated in the methods of the published article, the primary efficacy end point included only symptomatic calf DVT events, in accordance with the European Medicines Evaluation Agency and the ACCP guidelines. Besides, ultrasonography has been widely used in trials that evaluated thromboprophylaxis after knee (35) and ankle surgery (6).

Second, we strongly disagree with Dr. Geerts' statements that muscular venous thromboses are generally not even considered to be DVT and that they are usually not included as outcomes in clinical trials. According to Gray's Anatomy (7), muscular veins are classified as deep because they are tributaries of the popliteal vein and accompany the branches of the popliteal artery. As far as we know, none of the large trials of thromboprophylaxis after orthopedic surgery report the distribution of calf DVT. Rather, most trials report distal DVT outcomes detected by either venography or ultrasonography (6, 8, 9). Regardless, for the sake of discussion, we report more detail regarding the site of asymptomatic and symptomatic thromboses in the Table.


View this table:
[in this window]
[in a new window]

 
Table. Sites of Symptomatic and Asymptomatic Thromboses

 

Third, we think that a distinction between symptomatic and asymptomatic calf DVT is justified because of the European Medicines Evaluation Agency and ACCP requirements for ultrasonographic end points. We could not afford a double-blind, double-dummy design. To minimize bias, we used an assessor-blind strategy. We agree with Dr. Geerts' statement that asymptomatic patients were twice as likely as symptomatic patients to have leg thromboses. Many large trials that evaluate thromboprophylaxis report similar findings.

Fourth, it is not unusual for thromboprophylaxis trials to find statistically significant differences between groups in distal DVT, yet no statistically significant differences between groups for less frequent outcomes, such as death, symptomatic pulmonary embolism, symptomatic proximal DVT or pulmonary embolism, or all proximal DVT or pulmonary embolism. We note that the overall number of efficacy plus safety events in the 7-day LMWH group was about 50% less than that in the graduated compression stockings group (12 events vs. 23 events). Also, 4 of 6 safety events in the 7-day LMWH group were nonlife-threatening hemarthroses only.

Fifth, as stated in the published article, the study was designed as a 3-group trial, and the data and safety monitoring board halted the 14-day heparin group after the second interim analysis. The sample size calculations reported in the published paper were those originally calculated for the 3-group trial. The trial protocol specified a priori only symptomatic distal DVT and not asymptomatic distal DVT as a component of the primary end point.

In conclusion, we believe our results are valid, and we agree with Hull's editorial (10), which says that it is now time to change our clinical practice and to revisit policies that maximize bleeding avoidance and minimize thrombosis avoidance, because sudden death due to massive pulmonary embolism may well be the dominant harm rather than fatal bleeding due to thromboprophylaxis.


Author and Article Information
space
up arrowTop
dotAuthor & Article Info
down arrowReferences

From the University Hospital of Padua, 35128 Padua, Italy, and Hospital of Conegliano Veneto, 31015 Conegliano, Italy.

Potential Financial Conflicts of Interest: None disclosed.


References
space
up arrowTop
up arrowAuthor & Article Info
dotReferences

1.  Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:381S-453S. [PMID: 18574271].[Abstract/Free Full Text]

2.  Kearon C, Julian JA, Newman TE, Ginsberg JS. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med. 1998;128:663-77. [PMID: 9537941].[Abstract/Free Full Text]

3.  Wirth T, Schneider B, Misselwitz F, Lomb M, Tyl H, Egbring R. Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial. Arthroscopy. 2001;17:393-9. [PMID: 11288011].[Medline]

4.  Michot M, Conen D, Holtz D, Erni D, Zumstein MD, Ruflin GB. Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: A randomized trial of prophylaxis with lowmolecular weight heparin. Arthroscopy. 2002;18:257-63. [PMID: 11877611].[Medline]

5.  Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776-86. [PMID: 18579812].[Abstract/Free Full Text]

6.  Lapidus L, de Bri E, Ponzer S, Elvin A, Norn A, Rosfors S. High sensitivity with color duplex sonography in thrombosis screening after ankle fracture surgery. J Thromb Haemost. 2006;4:807-12. [PMID: 16634750].[Medline]

7.   Gray H. Gray's Anatomy. New York: Gramercy Books; 1918.

8.  Leizorovicz A, Kassai B, Becker F, Cucherat M. The assessment of deep vein thromboses for therapeutic trials. Angiology. 2003;54:19-24. [PMID: 12593492].[Medline]

9.  Kassa B, Boissel JP, Cucherat M, Sonie S, Shah NR, Leizorovicz A. A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients. Thromb Haemost. 2004;91:655-66. [PMID: 15045125].[Medline]

10.  Hull RD. Thromboprophylaxis in knee arthroscopy patients: revisiting values and preferences [Editorial]. Ann Intern Med. 2008;149:137-9. [PMID: 18626053].[Free Full Text]

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related articles in Annals:

Reviews
Noninvasive Diagnosis of Deep Venous Thrombosis
Clive Kearon, Jim A. Julian, M Math, Toni E. Newman, AND Jeffrey S. Ginsberg
Annals 1998 128: 663-677. [ABSTRACT][Full Text]  

Editorials
Thromboprophylaxis in Knee Arthroscopy Patients: Revisiting Values and Preferences
Russell D. Hull
Annals 2008 149: 137-139. [Full Text]  

Articles
Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy: A Randomized Trial
Giuseppe Camporese, Enrico Bernardi, Paolo Prandoni, Franco Noventa, Fabio Verlato, Paolo Simioni, Kadimashi Ntita, Giovanna Salmistraro, Christos Frangos, Franco Rossi, Rosamaria Cordova, Francesca Franz, Pietro Zucchetta, Dimitrios Kontothanassis, Giuseppe Maria Andreozzi, AND for the KANT (Knee Arthroscopy Nadroparin Thromboprophylaxis) Study Group
Annals 2008 149: 73-82. [ABSTRACT][SUMMARY][Full Text]  

Letters
Is Low-Molecular-Weight Heparin Suitable in All Patients Undergoing Knee Arthroplasty?
William Geerts
Annals 2008 149: 687. [Full Text]  






 Home | Current Issue | Past Issues | In the Clinic | ACP Journal Club | CME | Collections | Audio/Video | Mobile | Subscribe | Tools | Help | ACP Online 

Copyright © 2008 by the American College of Physicians.