Key Articles and Guidelines for the Prevention of Venous Thromboembolism

Paul P. Dobesh, Pharm.D., FCCP; Ann K. Wittkowsky, Pharm.D., FASHP, FCCP; Zachary Stacy, Pharm.D.; William E. Dager, Pharm.D., FCSHP; Stuart T. Haines, Pharm.D., FCCP; Larry M. Lopez, Pharm.D., FCCP; Edith Nutescu, Pharm.D., FCCP; Katherine W. Phillips, Pharm.D.; Toby C. Trujillo, Pharm.D.; Tom Vondracek, Pharm.D.


Pharmacotherapy. 2009;29(4):410-458. 

In This Article

Clinical Guidelines

Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines, 8th ed. Chest 2008;133(suppl 6):S381-453.

The 8th edition of the American College of Chest Physician (ACCP) guidelines, published in the summer of 2008, provides updated recommendations on the prevention of VTE in a wide variety of patient populations. In relation to other clinical practice guidelines on VTE prevention, the ACCP guidelines are the most comprehensive in terms of patient populations discussed, and often are the primary guideline source that most clinicians turn to regarding not only recommendations for the prevention of VTE, but also the appropriate use of antithrombotic agents in general. General recommendations include that every hospital should develop and implement a formal, institution-wide strategy to assess each patient for risk of VTE. The guidelines also encourage specific resources such as computer decision support, preprinted orders, and periodic audit to facilitate appropriate use of VTE prophylaxis. In a change from the 7th edition published in 2004, the 8th edition outlines a risk assessment scheme with three levels of risk, as opposed to four levels in the previous version. Low-risk patients include those undergoing minor surgery or patients who are fully mobile with medical conditions. Patients at moderate risk include most patients undergoing general surgery, open gynecologic surgery, or urologic surgery, as well as patients who are confined to bed rest with medical conditions. High-risk patients include those undergoing major orthopedic surgery and those with major trauma or spinal cord injury (SCI). General recommendations for the prevention of VTE depending on risk level are as follows: low risk—early ambulation, no specific preventive interventions needed; moderate risk—low-molecular-weight heparin (LMWH) at recommended doses, low-dose unfractionated heparin (UFH) given 2 or 3 times/day, fondaparinux, or mechanical methods in patients at high risk for bleeding; high risk—LMWH at recommended doses, fondaparinux, and warfarin with dosage titration to an international normalized ratio (INR) of 2.0-3.0. Low-dose UFH tends to be less effective than other pharmacologic options and should be used in conjunction with mechanical methods in high-risk patients. Given the comprehensive nature of the guidelines, the reader is referred to the parent document for more details regarding recommendations in specific patient populations.

Other recommendations should be noted. First, aspirin alone should never be recommended for prophylaxis in any patient group. Second, careful attention to renal function should be a factor in the selection of the specific agent for prophylaxis. When considering the use of agents that accumulate in the urine, health care practitioners should avoid the use of these agents, use a reduced dosage of the agent, or monitor the drug level or anticoagulant effect of the agent if applicable. Finally, when mechanical methods of prophylaxis are selected, careful attention should be paid to ensuring that they are used properly.

Committee on Practice Bulletins-Gynecology, American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 84: prevention of deep vein thrombosis and pulmonary embolism. Obstet Gynecol 2007; 110(2 pt 1):429-40.

Noting that the risk of developing VTE events can be significant in patients undergoing major gynecologic surgery (estimated rates of 15-40% in the absence of prophylaxis), the American College of Obstetricians and Gynecologists developed guideline to address recommendations for prevention of DVT and pulmonary embolism. In terms of defining the risk of VTE in gynecologic surgery, the authors make use of the four-level risk scheme that was found in the 7th edition of the ACCP guidelines published in 2004. Additional sections of the guideline discuss the available mechanical and pharma-cologic options for prophylaxis, as well as the role of hypercoagulable states in the development of VTE. Recommendations for VTE prophylaxis in gynecologic surgery based on risk are as follows: low risk—no specific prophylaxis intervention is recommended other than early ambulation; moderate risk—low-dose UFH 5000 U subcutaneously twice/day, dalteparin 2500 IU subcutaneously once/day, enoxaparin 40 mg subcutaneously once/day, graduated compression stockings (GCS), or intermittent pneumatic compression (IPC) devices are all equivalent options; high risk—low-dose UFH 5000 U subcutaneously 3 times/day, dalteparin 5000 IU subcutaneously once/day, enoxaparin 40 mg subcutaneously once/day, or IPC devices are all equivalent options; highest risk—low-dose UFH 5000 U subcutaneously 3 times/day, dalteparin 5000 IU subcutaneously once/day, enoxaparin 40 mg subcutaneously once/day, GCS, or IPC device plus recommended doses of low-dose UFH or LMWH are all equivalent options. recommendations are based on available literature in the gynecologic surgery arena for prevention of VTE.

Other recommendations should be noted. First, clinicians must appropriately consider the timing of dose administration and placement or removal of epidural anesthesia to minimize the risk of spinal hematoma. Second, if mechanical methods are to be used, they should be started at the beginning of surgery. Third, the authors do not recommend the discontinuation of hormone replacement therapy or contraceptives before gynecologic surgery because of the lack of evidence that discontinuation of these agents reduces the risk of postoperative VTE. Finally, it is reasonable for patients with a history of VTE to undergo testing for hypercoagulable conditions.

Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007;25:5490-505.

Recognizing that there exists a close relationship between cancer and the occurrence of VTE, and that there are some distinct aspects in prevention or treatment of VTE in patients being treated for malignancy, the American Society of Clinical Oncology developed this guideline, which encompasses recommendations for both prevention and treatment of VTE in patients with cancer. In addition, as a rationale for developing this document, the authors cite the relative lack of focus on patients with cancer in the 2004 version of the ACCP guidelines. Although patients with cancer share many of the same risk factors for VTE as the general population, specific risk factors in patients with malignancy include the following: time since cancer diagnosis, with the highest risk in the first 3-6 months; current metastatic disease; primary site of malignancy; active chemotherapy; and current or recent antiangiogenic therapy with thalidomide, lenalidomide, or bevacizumab.

The guideline was developed to address five primary questions on the prevention or treatment of VTE in patients with cancer. Only the questions related to prevention of VTE will be addressed here. First, hospitalized patients with cancer should be considered candidates to receive prophylaxis with low-dose UFH, LMWH, or fondaparinux in the absence of contraindications; this recommendation is based on trials of medically ill patients that contained subsets of patients with cancer. Second, routine prophylaxis for ambulatory patients without VTE and receiving chemotherapy is not indicated. The only exception is patients with myeloma who are receiving thalidomide or lenalidomide plus chemotherapy or dexamethasone. In those cases, an LMWH or warfarin (INR target 1.5) should be used for prevention of VTE. Finally, all patients undergoing major surgical interventions for malignant disease should receive prophylaxis with low-dose UFH, LMWH, or fondaparinux in the absence of contraindications. Prophylaxis should extend for at least 7-10 days. Mechanical methods of prophylaxis such as IPC may be added to pharmacologic agents but should not be used alone unless that patient is at high-risk for bleeding. In addition, it is reasonable to use LMWH for prophylaxis for up to 4 weeks after surgery in patients thought to be at very high risk, defined as major abdominal or pelvic surgery with residual malignant disease, obesity, or previous history of VTE.

Horlocker TT, Wedel D, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks—the second ASRA consensus conference on neuraxial anesthesia and anticoagulation. Reg Anesth Pain Med 2003;28: 172-97.

Despite being more than 5 years old, these recommendations remain the primary source for how to handle anticoagulation in patients also receiving neuraxial anesthesia and analgesia in the perioperative period. This issue first came to the forefront in the 1990s with the release of a number of case reports in which patients had developed spinal hematomas associated with the use of neuraxial anesthesia. Although LMWHs were used in many of these cases, it is important to note that many patients had hemostatic abnormalities and had received other agents that may affect hemostasis (aspirin, nonsteroidal antiinflammatory drugs, UFH). Common themes of all the recommendations include consideration for the timing of needle placement, epidural catheter removal, and drug administration. In patients receiving recent fibrinolytic therapy, the use of spinal or epidural anesthesia should generally be avoided. In addition, general guidelines for fibrinolytics suggest avoiding their use in patients with puncture of noncompressible vessels in the past 10 days. In patients receiving low-dose UFH subcutaneously, there is no contraindication to neuraxial techniques, as the risk for developing spinal hematoma appears to be minimal. In patients who are to receive intraoperative anticoagulation with UFH, the UFH infusion should be started at least 1 hour after needle placement, and indwelling catheters should be removed 2-4 hours after discontinuation of the UFH infusion and only after the patient’s coagulation status has been assessed.

In patients for whom LMWH is being used for VTE prophylaxis, concomitant use of other oral antiplatelet and anticoagulant drugs should be avoided. Also, needle placement should be delayed until 10-12 hours after the dose of LMWH, when LMWH is being started preoperatively. If LMWH has been administered in treatment doses, needle placement should commence at least 24 hours after the last dose. Finally, postoperative LMWH prophylaxis should begin no sooner than 2 hours after needle or indwelling catheter removal. In patients who had been receiving long-term warfarin therapy or are receiving warfarin therapy for VTE prophylaxis, long-term warfarin therapy ideally should be held for a minimum of 4-5 days before surgery, and assessment of the INR should be undertaken before needle insertion. In patients receiving preoperative warfarin for prophylaxis, an INR should be checked before needle placement if it has been over 24 hours since the first dose, or if two or more doses of warfarin have been given. For patients with an indwelling catheter who are receiving warfarin, the catheter should be removed when the INR is less than 1.5. The use of fondaparinux and neuraxial anesthesia or analgesia should follow the conditions used in clinical trials as closely as possible. Additional recommendations are provided regarding the use of antiplatelet agents and herbal therapy. In either case, significant risk for spinal hematoma is noted only with the use of adenosine diphosphate antagonists, such as ticlopidine and clopidogrel, and glycoprotein IIb-IIIa antagonists.

American Academy of Orthopedic Surgeons. Clinical guideline on prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. Available from Accessed September 27, 2008.

The guidelines from the American Academy of Orthopedic Surgeons (AAOS) have generated a high level of controversy and debate. Although the guidelines have not been peer reviewed, nor have they been published in a peer-reviewed journal, the AAOS thoroughly documents the systematic process used to produce their conclusions. Therefore, readers can make their own interpretations and conclusions regarding the methods used as if the document were a published article. Important differences guide the development of AAOS recommendations as compared with other guidelines that address VTE prevention. First, the authors of the AAOS guidelines question the relationship between the prevention of DVT and a subsequent decrease in pulmonary embolism. Whereas most consensus guidelines and systemic reviews take the approach that interventions that have supporting evidence for lowering the risk of DVT will also lower the risk of pulmonary embolism, the authors of AAOS guidelines state that there is little compelling literature validating this relationship. Second, as such, the authors of the AAOS guidelines by default place little emphasis on the complications of DVT development such as venous insufficiency, postthrombotic syndrome, and recurrent events. Finally, although bleeding is discussed and emphasized in other clinical guidelines on VTE prevention, the AAOS authors place a higher degree of emphasis on the risk of bleeding in the development of their recom-mendations, citing that bleeding may result in chronic joint stiffness, infection, and potentially a return to surgery for evacuation of hematomas. The authors also speculate that the reported rate of bleeding in clinical trials is an underestimate of real-world experience. Consequently, the recommendations for VTE prevention in this clinical guideline focus solely on an intervention’s capacity to reduce the frequency of clinical pulmonary embolism, as well as to cause major bleeding.

The availability of extensive literature on the prevention of DVT by various pharmacologic modalities is given minimal consideration. The consensus document provides recommendations for the preoperative, intraoperative, and postoperative periods. The recommendations for prevention of symptomatic pulmonary embolism in patients at standard risk for both pulmonary embolism and major bleeding include aspirin 325 mg/day for up to 6 weeks, LMWH dosed according to the package insert for 7-12 days, fondaparinux dosed according to the package insert for 7-12 days, and warfarin with goal INR less than 2.0 for 2-6 weeks. In patients with an elevated risk for pulmonary embolism but standard risk for major bleeding, only LMWH, fondaparinux, or warfarin is recommended. In patients at high risk for bleeding, regardless of the risk of pulmonary embolism, only aspirin and warfarin are recommended as options. It is important to note that while aspirin has been shown to be effective at preventing DVT compared with placebo, it has consistently been shown to be inferior to anticoagulant options at preventing DVT. Hence, the recommendation for the use of aspirin for prophylaxis is not found in other clinical guidelines and often is actively discouraged. Resolving the discrepancy over recommendations for aspirin use for prophylaxis in various clinical guidelines continues to be one of the challenges in improving the rates of VTE prophylaxis for patients requiring acute care.

Kaufman JA, Kinney TB, Streiff MB, et al. Guidelines for the use of retrievable and convertible vena cava filters: report from the Society of Interventional Radiology multidisciplinary consensus conference. Surg Obes Relat Dis 2006;2:200-12.

The goal of this consensus document was to provide clinical guidance to physicians regarding the appropriate use of vena cava filters, especially those that may be removed after a period of time. In 2003, the United States Food and Drug Administration approved changes to instructions for several available vena cava filters such that they could be used on a temporary basis. Subsequently, the overall use of vena cava filters increased, especially with nonpermanent devices. Although physicians now had technical instructions on how to place and remove nonpermanent filters, no information was available regarding which patients could be candidates for a removable filter or what specific considerations to evaluate before placing a removable filter. To further complicate matters, available literature addressing the use of vena cava filters, either permanent or removable, is sparse at best, with most reports being in the form of observational studies.

In 2005, the Society of International Radiology convened a multidisciplinary consensus conference to develop guidance for the use of nonpermanent filters. The consensus group advocates several general principles. The primary means of prophylaxis and treatment of VTE are pharmacologic in nature. The sole indication for use of a vena cava filter is the prevention of pulmonary embolism in patients who cannot receive pharmacologic prophylaxis or treatment, or who despite pharmacologic prophylaxis or treatment remain at unacceptably high risk for pulmonary embolism. The indications for use of a nonpermanent vena cava filter are no different from those for the use of permanent filters. The decision to use a nonpermanent filter should be based on the anticipated required duration of protection from pulmonary embolism, as well as the time period in which pharmacologic therapy may be contraindicated—when either or both of these are transient, the use of a retrievable filter can be justified. Regardless of whether a filter is in place, pharmacologic prophylaxis or treatment should be started as soon as it is determined safe to do so. And finally, whereas the placement of vena cava filters to prevent pulmonary embolism in patients who have no objectively confirmed acute DVT events is controversial and has little support in the literature, there are patient populations in which some support is available and use seems reasonable. These include those who sustained major trauma, critically ill patients with a history of VTE and contraindications to anticoagulation, and those undergoing bariatric surgery. The guideline contains additional information regarding the removal of nonpermanent vena cava filters. Important management points include the absence of a need to discontinue therapeutic anticoagulation during the removal of a temporary filter, and, after filter retrieval, patients should be treated according to their VTE status according to standards of care as delineated in national guidelines.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.