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Is Low-Molecular-Weight Heparin Suitable in All Patients Undergoing Knee Arthroplasty?
- Giuseppe Camporese, MD;
- Franco Noventa, MD; and
- Enrico Bernardi, MD, PhD
- From the University Hospital of Padua, 35128 Padua, Italy, and Hospital of Conegliano Veneto, 31015 Conegliano, Italy.
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.
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.
Giuseppe Camporese, MD
Franco Noventa, MD
University Hospital of Padua
35128 Padua, Italy
Enrico Bernardi, MD, PhD
Hospital of Conegliano Veneto
31015 Conegliano, Italy
Article and Author Information
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Potential Financial Conflicts of Interest: None disclosed.
