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University of Toronto, Toronto, Canada
Correspondence to: William Geerts, MD, FCCP, Thromboembolism Program, Sunnybrook & Women’s College Health Sciences Centre, Room D674, 2075 Bayview Ave, Toronto, ON, Canada MVN 3M5
To the Editor:
We thank Dr. Lotke (June 2005)1 for raising a number of important issues about the development of guideline recommendations for thromboprophylaxis. While Dr. Lotke contends that internists undervalue postoperative bleeding related to anticoagulant prophylaxis, we are not aware of any evidence that supports this statement. In contrast, the American College of Chest Physicians (ACCP) thromboprophylaxis guideline process placed a high value on minimization of bleeding complications when making its recommendations.2 The chapter authors included three surgeons, two of whom are practicing orthopedic surgeons. Furthermore, before finalizing the orthopedic surgery sections, we obtained formal reviews from 16 experts who were external to the ACCP thromboprophylaxis committee; 10 of these were orthopedic surgeons. Thus we believe that the values we assigned to bleeding complications and prevention of deep vein thrombosis (DVT) are representative of the orthopedic community and their patients.
As an example of the priority we placed on avoiding bleeding due to thromboprophylaxis, the use of low-molecular-weight heparins (LMWHs) was rated over fondaparinux in hip and knee arthroplasty because of slightly greater bleeding with the latter (despite an overall 50% relative risk reduction for DVT prevention with fondaparinux compared with LMWH).3 We also ranked extended prophylaxis with LMWH over vitamin K antagonists based on greater bleeding risks with the latter agents.4
We do agree that anticoagulant prophylaxis should be used cautiously in patients at higher risk of bleeding than those included in clinical trials. However, there is little evidence that age is an independent predictor of bleeding in such patients, and age was not an exclusion criteria in most of the clinical trials. While thromboprophylaxis should attempt to keep the risk of patient-important bleeding to a minimum, we should not lose sight of the need to prevent DVT in major orthopedic surgery patients and thereby to reduce the complications of acute DVT and pulmonary embolism as well as the long-term sequellae of chronic venous insufficiency and pulmonary hypertension.
Asymptomatic DVT is frequently used as a surrogate for patient-important outcomes in thromboprophylaxis trials.5 Clearly, symptomatic thromboembolic events are less common than asymptomatic DVT if a highly sensitive diagnostic test such as contrast venography is used to routinely screen patients. We agree with Dr. Lotke that the ratio of asymptomatic DVT to symptomatic venous thromboembolism (VTE) varies somewhat from one patient group to another, although this relationship has been shown to range from 5:1 to 10:1 across a spectrum of patient groups.2
Dr. Lotke is, however, incorrect in his view that reduction in asymptomatic DVT is not correlated with reduction in pulmonary embolism (PE). This issue is discussed in detail in sections 1.2 and 1.4.2 of our chapter. Although most thromboprophylaxis trials are underpowered to show a statistically significant reduction in symptomatic VTE, large trials and metaanalyses demonstrate similar risk reductions for this outcome compared with those observed for asymptomatic DVT.
For example, nine randomized trials, including a total of 4,000 patients, compared in-hospital thromboprophylaxis with prophylaxis extended to approximately 1 month after discharge following hip or knee arthroplasty.6 The relative risk reductions with extended prophylaxis were 52% for venographic DVT and 62% for symptomatic VTE. In the Pentasaccharide in Hip-Fracture Surgery Plus trial,7 extended thromboprophylaxis in hip fracture patients was associated with a 96% reduction in venographic DVT and an 89% reduction in symptomatic VTE, both statistically significant benefits of prophylaxis. Although we support the design and conduct of large randomized trials of thromboprophylaxis using patient-important outcomes, the prevention of asymptomatic DVT is highly correlated with prevention of symptomatic PE. The attempt by Dr. Lotke to relate the incidence of asymptomatic DVT in high-risk patients receiving no prophylaxis to fatal PE rates in patients receiving prophylaxis is misleading and does not assist the discussion of these issues.
The ACCP Antithrombotic Therapy Guidelines Group continue to work with the orthopedic community to develop guidelines that are both evidence-based and useful for practicing orthopedic surgeons. The principal challenge for all of us is to develop effective strategies to implement such guidelines universally and, thereby, to provide the most effective, safe, and cost-effective protection for our patients.
References
This article has been cited by other articles:
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  C. Sinclair and N. Eipe Recurrent postoperative deep vein thrombosis in a patient with obstructive sleep apnea and malignant hyperthermia susceptibility Can J Anesth, December 1, 2007; 54(12): 1032 - 1033. [Full Text] [PDF]
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