Prevention of Venous Thromboembolism in Major Orthopaedic Surgery: The 8th ACCP Guidelines

William Geerts, M.D.
Thromboembolism Programme, Sunnybrook Health Sciences Centre
University of Toronto
Toronto, ON

Rationale for Routine Thromboprophylaxis in Major Orthopaedic Surgery
Because venous thromboembolism (VTE) is one of the most common complications following major orthopaedic surgery and is associated with both short- and long-term morbidity and occasional fatal outcome, routine prophylaxis has been the key to reducing the burden of this disease for more than 20 years1-3. Numerous clinical trials confirm the effectiveness, safety, and cost-effectiveness of thromboprophylaxis in a broad spectrum of patient groups. The use of thromboprophylaxis has been shown to reduce the risk of DVT, proximal DVT, PE, and fatal PE by more than 60% while the risk of clinically-important bleeding is low with anticoagulant prophylaxis and is similar to the risk seen in patients not receiving prophylaxis or receiving mechanical prophylaxis1. Orthopaedic surgery is the clinical area with the highest thrombosis risk, the largest number of recent clinical trials and with the greatest adherence to recommended prophylaxis. With the routine use of thromboprophylaxis in these patients, fatal PE is very uncommon, although symptomatic VTE continues to be reported in 1-5% of arthroplasty patients within three months after surgery1,4.

The ACCP Guidelines on the Prevention of VTE in Orthopaedic Surgery
The American College of Chest Physicians (ACCP) Guidelines on the Prevention of VTE are prepared by a multidisciplinary, international group of clinician-methodologists, including orthopaedic surgeons1. Because such a large number of high-quality thromboprophylaxis studies are available, the ACCP recommendations are based primarily on the results of randomized trials in which all VTE (symptomatic and asymptomatic) and bleeding are the primary outcomes. In addition to extensive formal peer review, the primary principle of the ACCP guidelines is to have a transparent link between the evidence and the graded recommendations. A summary of the 2008 ACCP guidelines on the prevention of VTE in major orthopaedic surgery is found in the Table. 
table_bayer.jpg

Elective Hip Replacement (THR)
Based on a large number of randomized trials, three prophylaxis options are recommended following THR: LMWH, fondaparinux and warfarin (target INR 2-3)1. Aspirin, elastic stockings, pneumatic compression devices, and low dose heparin are not recommended as sole methods of prophylaxis since they have each shown inferior protection compared with the recommended options. In Canada, LMWH and warfarin are the most common prophylaxis modalities in THR and TKR patients, used by approximately 70% and 25% of patients, respectively5. The disadvantages of warfarin prophylaxis include: 1) its delayed onset of action for several days after surgery, 2) reduced efficacy compared with LMWH (with similar bleeding rates), 3) marked variability in dose among patients, 4) need for frequent laboratory monitoring, and 5) the complexity of both in-patient and post-discharge supervision. Although a number of multimodal thromboprophylaxis strategies are likely to be effective (for example, the combination of epidural anesthesia plus pneumatic compression devices, plus elastic stockings, plus aspirin, plus anticoagulant prophylaxis in patients considered to be at particularly high risk), they are not included in the recommendations for the following reasons: 1) there are very few randomized trials comparing these regimens to any of the recommended options, 2) they are more complex and more costly than single modality options.

Total Knee Replacement (TKR)
The risk of calf DVT is somewhat greater after TKR than after THR4. However, proximal DVT is less common following TKR and the duration of risk appears to be shorter6. The recommended methods of prophylaxis are also LMWH, fondaparinux and warfarin (target INR 2-3)1. LDH, aspirin and the VFP are not recommended options in this patient group because the other options are more efficacious.

Hip Fracture Surgery (HFS)
Asymptomatic DVT rates after HFS are comparable to those seen after THR. However, symptomatic VTE and fatal PE are more common among hip fracture patients presumably because of their advanced age, reduced mobility, multiple comorbidities, and the double thromboembolic insults of the fracture itself and its surgical repair7. Despite the high risk of VTE, there are many fewer trials of prophylaxis after HFS than after THR. Recommended prophylaxis options are fondaparinux, LMWH, warfarin (target INR 2-3), and low dose heparin1. Although the largest clinical trial in HFS showed that fondaparinux was more efficacious than enoxaparin without increased bleeding, LMWH remains a recommended option based on extrapolation from THR studies and its lower cost. If surgical repair is likely to be delayed, thromboprophylaxis should be administered during the preoperative period using a short-acting anticoagulant such as LMWH given in the evening to avoid missing any doses. f

Duration of Thromboprophylaxis After Major Orthopaedic Surgery
Approximately two-thirds of all the symptomatic thromboembolic events that occur following major orthopaedic surgery are diagnosed after the patient has left hospital1,6,8. The increased risk of VTE continues for up to three months after THR and up to one month after TKR6. Multiple studies after major orthopaedic surgery have compared the in-hospital use of thromboprophylaxis with prophylaxis that extends for four to six weeks after surgery9,10. A meta-analysis of nine of these randomized trials, which included a total of 4,000 patients, demonstrated a 51% risk reduction for venographic DVT and a 61% risk reduction for symptomatic VTE with extended prophylaxis without an increase in bleeding9. Since there is currently no method to reliably identify the orthopaedic surgery patients who will develop post-discharge VTE, extended prophylaxis is recommended for all patients undergoing THR, TKR and HFS1,11. Although four to six weeks of prophylaxis is superior to in-hospital prophylaxis only, the optimal duration of prophylaxis between two weeks and six weeks remains uncertain; this remains a local policy decision for the unit or the individual patient.

References

  1. Geerts W.H., Bergqvist D., Pineo G.F., et al. Prevention of venous thromboembolism. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S
  2. National Institutes of Health Consensus Conference. Prevention of venous thrombosis and pulmonary embolism. JAMA 1986;256:744-749
  3. Lieberman J.R., Hsu WK. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am 2005;87:2097-2112
  4. Pellegrini V.D., Donaldson C.T., Farber D.C., et al. The Mark Coventry Award. Prevention of readmission for venous thromboembolism after total knee arthroplasty. Clin Orthop 2006;452:21-27
  5. Canadian Institute for Health Information. Canadian Joint Replacement Registry (CJRR) 2007 Annual Report - Hip and Knee Replacements in Canada. Ottawa: CIHI, 2008
  6. White R.H., Romano P.S., Zhou H., et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998;158;1525-1531
  7. Hitos K., Fletcher J.P. Venous thromboembolism and fractured neck of femur. Thromb Haemost 2005;3:185-187
  8. Bjornara B.T., Gudmundsen T.E., Dahl O.E. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br 2006;88:386-391
  9. Eikelboom J.W., Quinlan D.J., Douketis J.D. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomized trials. Lancet 2001;358:9-15
  10. Douketis J.D., Eikelboom J.W., Quinlan D.J., et al. Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes. Arch Intern Med 2002;162:1465-1471
  11. Beksac B., Della Villa A.G., Salvati E.A. Thromboembolic disease after total hip arthroplasty: who is at risk? Clin Orthop 2006;453:211-224

APPENDIX: 8th ACCP Major Orthopaedic Surgery Recommendations
[orthopaedic is spelled ‘orthopedic' in the Appendix due to reprint restrictions]

3.1    Elective Hip Replacement

3.1.1. For patients undergoing elective THR, we recommend the routine use of one of the following anticoagulant options: (1) LMWH (at a usual high-risk dose, started 12 h before surgery or 12 to 24 h after surgery, or 4 to 6 h after surgery at half the usual high-risk dose and then increasing to the usual high-risk dose the following day); (2) fondaparinux (2.5 mg started 6 to 24 h after surgery); or (3) adjusted-dose VKA started preoperatively or the evening of the surgical day (INR target, 2.5; INR range, 2.0 to 3.0) [all Grade 1A].

3.1.2. For patients undergoing THR, we recommended against the use of any of the following: aspirin, dextran, LDUH, GCS, or VFP as the sole method of thromboprophylaxis [all Grade 1A].

3.1.3. For patients undergoing THR who have a high risk of bleeding, we recommend the optimal use of mechanical thromboprophylaxis with the VFP or IPC [Grade 1A]. When the high bleeding risk decreases, we recommend that pharmacologic thromboprophylaxis be substituted for or added to the mechanical thromboprophylaxis [Grade 1C]. 

3.2    Elective Knee Replacement

3.2.1. For patients undergoing TKR, we recommend routine thromboprophylaxis using LMWH (at the usual high-risk dose), fondaparinux, or adjusted-dose VKA (INR target, 2.5; INR range, 2.0 to 3.0) [all Grade 1A].

3.2.2. For patients undergoing TKR, the optimal use of IPC is an alternative option to anticoagulant thromboprophylaxis [Grade 1B].

3.2.3. For patients undergoing TKR, we recommend against the use of any of the following as the only method of thromboprophylaxis: aspirin [Grade 1A], LDUH [Grade 1A], or VFP [Grade 1B].

3.2.4. For patients undergoing TKR who have a high risk of bleeding, we recommend the optimal use of mechanical thromboprophylaxis with IPC [Grade 1A] or VFP [Grade 1B]. When the high bleeding risk decreases, we recommend that pharmacologic thromboprophylaxis be substituted for or added to the mechanical thromboprophylaxis [Grade 1C]. 

3.4   Hip Fracture Surgery

3.4.1. For patients undergoing HFS, we recommend routine thromboprophylaxis using fondaparinux [Grade 1A], LMWH [Grade 1B], adjusted-dose VKA (INR target, 2.5; INR range, 2.0 to 3.0) [Grade 1B], or LDUH [Grade 1B].

3.4.2. For patients undergoing HFS, we recommend against the use of aspirin alone [Grade 1A].

3.4.3. For patients undergoing HFS in whom surgery is likely to be delayed, we recommend that thromboprophylaxis with LMWH or LDUH be initiated during the time between hospital admission and surgery [Grade 1C].

3.4.4. For patients undergoing HFS who have a high risk of bleeding, we recommend the optimal use of mechanical thromboprophylaxis [Grade 1A]. When the high bleeding risk decreases, we recommend that pharmacologic thromboprophylaxis be substituted for or added to the mechanical thromboprophylaxis [Grade 1C]. 

3.5 Other Thromboprophylaxis Issues in Major Orthopedic Surgery

3.5.1 Commencement of Thromboprophylaxis

3.5.1.1. For patients receiving LMWH as thromboprophylaxis in major orthopedic surgery, we recommend starting either preoperatively or postoperatively [Grade 1A].

3.5.1.2. For patients receiving fondaparinux as thromboprophylaxis in major orthopedic surgery, we recommend starting either 6 to 8 h after surgery or the next day [Grade 1A].

3.5.2 Screening for DVT before Hospital Discharge

3.5.2. For asymptomatic patients following major orthopedic surgery, we recommend against the routine use of DUS screening before hospital discharge [Grade 1A].

3.5.3 Duration of Thromboprophylaxis

3.5.3.1. For patients undergoing THR, TKR, or HFS, we recommend thromboprophylaxis with one of the recommended options for at least 10 days [Grade 1A].

3.5.3.2. For patients undergoing THR, we recommend that thromboprophylaxis be extended beyond 10 days and up to 35 days after surgery [Grade 1A]. The recommended options for extended thromboprophylaxis in THR include LMWH [Grade 1A], a VKA [Grade 1B], or fondaparinux [Grade 1C].

3.5.3.3. For patients undergoing TKR, we suggest that thromboprophylaxis be extended beyond 10 days and up to 35 days after surgery [Grade 2B]. The recommended options for extended thromboprophylaxis in TKR include LMWH [Grade 1C], a VKA [Grade 1C], or fondaparinux [Grade 1C].

3.5.3.4. For patients undergoing HFS, we recommend that thromboprophylaxis be extended beyond 10 days and up to 35 days after surgery [Grade 1A]. The recommended options for extended thromboprophylaxis in HFS include fondaparinux [Grade 1A], LMWH [Grade 1C], or a VKA [Grade 1C].

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