Healio
Healio
February 01, 2003
11 min read
Save

Managing Thromboembolic Risk in Hip and Knee Arthroplasty: State of the Art

ABSTRACT

Deep vein thrombosis and pulmonary embolism are major causes of morbidity and mortality after knee and hip arthroplasty in the United States. Although patients frequently receive prophylaxis for thromboembolism postarthroplasty, surgeons vary in their choice of modality and often use suboptimal strategies due to the possibility of provoking postoperative bleeding. This article discusses the rationale for the prevention of venous thromboembolism and offers an overview of clinical recommendations for prophylaxis in knee and hip replacement surgery. Supporting medical evidence for these recommendations is described. A summary of current prophylactic regimens and discussion of duration of therapy are also presented.




Patients who undergo major lower extremity orthopedic surgery are among those considered to be at greatest risk for venous thromboembolism.1 Many of these patients may have compounded risks attributable to acquired or genetic factors. Some of the risks include advanced age (>40 years), stroke, obesity, trauma, pregnancy, cancer, oral contraception, and hormone replacement therapy, as well as inherited coagulation defects, which are present in 3%-6% of the general population.2,3

The significant prevalence of deep vein thrombosis and pulmonary embolism in knee and hip replacement patients has been well documented. Some data suggest a deep vein thrombosis rate as high as 84% when prophylaxis is not administered to patients undergoing total knee replacement (TKR) and a rate of 57% after total hip replacement (THR) (Table 1).1 The prevalence of total pulmonary embolism in patients undergoing TKR is less certain, but studies have reported rates of 0%-12% for total pulmonary embolism and 0%-1.5% for fatal occurrences.4 Rates of total and fatal pulmonary embolism for THRs are reported to be 0.7%-30% and 0.1%-0.4%, respectively.1 Results of a retrospective study examining the records of 24,059 patients undergoing TKR demonstrated a 2.1% prevalence of deep vein thrombosis or pulmonary embolism within 3 months of surgery.5

Prophylaxis to reduce the risk of thromboembolism is necessary to prevent potentially catastrophic manifestations. Fatal pulmonary embolism is the most preventable cause of death during hospitalization.6 An estimated 600,000 patients with deep vein thrombosis will develop pulmonary embolism, which causes death in <200,000.7 Secondary complications, such as postphlebitic syndrome and pulmonary hypertension, contribute to long-term morbidity and mortality.

This evidence has led the American College of Chest Physicians to recommend prophylaxis as the standard practice for patients undergoing TKR and THR (Table 2).8 The silent nature of thromboembolic disease, its widespread prevalence and rapid onset, and its potentially catastrophic consequences in otherwise healthy patients support the need for prophylaxis.

Surveys suggest that most orthopedic surgeons are aware of the risk for venous thromboembolism, but approaches to its prevention vary. A survey related to the prevention of venous thromboembolism in patients undergoing THR and TKR was conducted among members of the American Association of Hip and Knee Surgeons. Results of this survey (33% response rate) showed that prophylaxis was prescribed for 100% of patients during the course of hospitalization. The survey also found that orthopedic surgeons used variable prophylactic methods and regimens.9 Results from a 1996 survey of the Fellows of the American College of Surgeons demonstrated less universal use of prophylaxis (96%; N=1145) among surgeons in general,3 but these findings represent an improvement over the 90% who reported prophylactic use in 1994.3 Most of the surgeons surveyed (52%) preferred physical prophylactic methods over pharmacologic agents.

Although these reports indicate that orthopedic surgeons include prophylaxis in their treatment regimens, variations in clinical practice suggest that they may do so suboptimally, underutilizing available modalities or failing to follow established guidelines. Some surgeons believe that surgical advances obviate the need for caution. Other surgeons contend that the incidence of thromboembolism is decreasing. The reduction is a direct result of successful prophylaxis of patients at risk, as well as declining autopsy rates reporting venous thromboembolism in the United States.7 Orthopedic surgeons are concerned about major postoperative bleeding and thrombocytopenia with commonly used pharmacologic agents.10 Cost also has been cited as a disincentive for the use of thromboprophylaxis. However, pharmacoeconomic analyses consistently report that thromboprophylaxis is highly cost-effective.1 Finally, some physicians fail to use prophylaxis based on the individual practice experience and subjective perception that venous thromboembolism rarely occurs. Aggregate prevalence data suggest otherwise. Therefore, reticence on the part of physicians may account for the lack of adherence to the clinical guidelines and suggests that individual bias is overshadowing the medical evidence.

Nonpharmacologic Prophylactic Modalities

Mechanical nonpharmacologic prophylaxis methods, such as intermittent pneumatic compression devices and foot pumps, increase the speed of venous flow and the volume of blood returned from the extremity to the heart. In addition, these nonpharmacologic modalities produce endothelial-induced changes in the clotting cascade that decrease the risk for a thromboembolic phenomenon. Therefore, pneumatic compression devices often play a role in thromboprophylaxis. A disadvantage of mechanical devices is that the patient leaves the hospital unprotected, as mechanical devices cannot be easily used in the home. Pneumatic compression devices can play a role in the prevention of deep vein thrombosis, particularly in patients undergoing spinal or epidural anesthesia or in the continued epidural use for pain control, when pharmacologic anticoagulation is difficult.11

When used in combination with pharmacologic agents, pneumatic compression devices have been shown to decrease the rate of proximal deep vein thrombosis to 0% in one study in patients undergoing knee replacement.11 When used independently of pharmacologic agents, elastic stockings, intermittent pneumatic compression, and early ambulation have reduced the risk of deep vein thrombosis by 25%-82%.7 Clinical evidence prompted a recommendation for the use of elastic stockings or intermittent pneumatic compression as an adjuvant therapy in hip replacement (grade C), and intermittent compression devices as an alternative to pharmacotherapy in TKR (grade 1B).1

table

Pharmacologic Prophylactic Agents

Although several agents have been shown to reduce the risk of thromboembolic disease, no single modality meets all of the ideal clinical prophylactic requirements: low risk of side effects, practicality of use, ease of administration and monitoring, and cost-efficiency. Orthopedic surgeons adopt single and additive mechanical and pharmacologic protocols with different time frames for patient exposure.

Low-molecular-weight heparins and the vitamin K antagonist warfarin are the mainstays of prophylaxis after TKR or THR. Derivatives of unfractionated heparin, the low-molecular-weight heparins (ie, enoxaparin, dalteparin, nadroparin, and tinzaparin), have a longer half-life than unfractionated heparin, as well as better bioavailability. Low-molecular-weight heparins can be administered subcutaneously in a weight-adjusted, twice-daily dose, and do not require routine coagulation monitoring. This makes low-molecular-weight heparins suitable for extended prophylaxis at home in selected patients.12-15

Either a low-molecular-weight heparin or an adjusted-dose warfarin is recommended for prophylaxis in THR and TKR (grade 1A) and hip fracture (grade 1B).1 After an evalutaion of the two agents, the American College of Chest Physicians concluded that “low-molecular-weight heparin is significantly more effective than warfarin in preventing asymptomatic and symptomatic inhospital venous thromboembolism” due to the more rapid onset of anticoagulant activity with low-molecular-weight heparin than with warfarin.1 The risk of surgical site bleeding and wound hematoma was determined to be slightly higher with low-molecular-weight heparins.1 The American College of Chest Physicians recommends that the selection of low-molecular-weight heparin or warfarin prophylaxis be made on an institutional level and, on occasion, an individual level based on cost, convenience, the availability of an infrastructure to provide safe oral anticoagulation, the duration of planned prophylaxis, and potential bleeding and thrombosis risks.1

Both warfarin and low-molecular-weight heparin therapy have advantages. Warfarin may be taken orally but patients on warfarin require careful monitoring, which may be problematic in home use. Although low-molecular-weight heparin does not require routine coagulation monitoring, it may be inappropriate for patients who cannot self-manage dosing after leaving the hospital because of physical status or socioeconomic factors.15

The finding by the American College of Chest Physicians that a low-molecular-weight heparin is more efficacious than warfarin in THR surgery is based on careful evaluation of the medical literature (Table 3).1,8 Combined data from these five studies16-20 show significant reductions in relative risk for venous thromboembolism with the use of a low-molecular-weight heparin versus warfarin. No clinical investigation comparing the two types of agents in TKR has reported clinical venous thromboembolism as the primary outcome. The lack of such data prevented the American College of Chest Physicians from recommending low-molecular-weight heparin therapy over warfarin for TKR. However, based on the available evidence, the American College of Chest Physicians suggests that low-molecular-weight heparin therapy is likely to be more effective than warfarin for TKR, but may cause more surgical site bleeding.1

Recommendations for the use of traditional heparins in orthopedic surgery vary by procedure. Adjusted-dose heparin administered preoperatively is given a grade 2A recommendation for use in THR, whereas low-dose unfractionated heparin receives a grade 2B recommendation for use in hip fracture surgery.1 Low-dose unfractionated heparin is not recommended for prophylaxis in TKR.

Once widely used, aspirin is not recommended for use in THR or TKR or in the management of hip fracture. Although clinical data from the Pulmonary Embolism Prevention Trial Study of 13,356 hip fracture patients demonstrated that aspirin reduced rates of pulmonary embolism and deep vein thrombosis by at least one-third,21 the use of aspirin was associated with an increased incidence of cardiac events, gastrointestinal bleeding, and wound bleeding.1,21 The recommendation to refrain from using aspirin for anticoagulation is based on this report of negative clinical outcomes, without supportive data other than data from prospective randomized trials.

Newer agents for the prevention of thromboembolism include fondaparinux, which is a pentasaccharide. Fondaparinux acts as a selective factor Xa inhibitor. After extensive phase III trials, it was approved for THR, TKR, and hip fracture surgery, but has slightly increased bleeding rates over the most commonly used low-molecular-weight heparin, enoxaparin.22 Fondaparinux has an 18-hour half-life and no antidote at this time.23 The orally active thrombin inhibitor, ximelagatran, is under investigation for use in venous thromboembolism prophylaxis.24

Prophylactic Regimens

The optimal regimen of prophylaxis for venous thromboembolism after THR or TKR is uncertain. Therefore, regimens vary significantly. In Europe, prophylaxis is initiated 12 hours before surgery. In North America, a low-molecular-weight heparin is administered at 6-24 hours postoperative. Other regimens involve initiation of therapy either earlier than 12 hours before surgery or postoperatively. Although direct comparisons among the three strategies are sparse, one analysis undertaken by Strebel et al25 suggests that there is no significant difference in the incidence of venous thromboembolism with the use of preoperative or postoperative regimens. Warfarin can be initiated 1 day before surgery, on the day of surgery, or 1 day after surgery, depending on the physician’s preference.

In the United States, orthopedic surgeons tend to delay prophylaxis with low-molecular-weight heparins beyond established protocols, which call for therapy to be initiated within 6-24 hours after surgery, because of the increased risk for major bleeding in their patients. However, data from meta-analyses and placebo-controlled, double-blind, randomized trials of low-dose unfractionated heparin or low-molecular-weight heparin have shown either no increase or a small increase in the absolute rates of major bleeding with the use of these agents.1

table

Duration of Therapy

Because hospital stays for arthroplasty have decreased by .50% from what they were a decade ago, outpatient continuation of prophylaxis should be considered. Prospective studies report that fatal pulmonary embolism may occur 5 weeks after THR.26 Emerging data suggest that continued prophylaxis after the hospital stay may offer additional protection. The American College of Chest Physicians makes a grade 2A recommendation that low-molecular-weight heparin therapy be administered beyond 7-10 days after major orthopedic surgery of the lower extremity.1

To evaluate the existing medical evidence regarding the risks and benefits of prolonged outpatient prophylaxis, Hull et al27 conducted a systematic review of randomized, controlled trials that compared extended out-of-hospital prophylaxis with a low-molecular-weight heparin versus placebo in patients undergoing elective THR. The investigators found that extended prophylaxis was effective and safe regardless of variations in clinical practice and length of hospital stay. The combined results from the reviewed studies suggested that patients undergoing THR would benefit from extended outpatient prophylaxis.27 Differences in the major outcomes of all episodes of deep vein thrombosis, proximal venous thrombosis, and symptomatic venous thromboembolism during the out-of-hospital time interval were highly significant across six total THR studies. The combined incidence of patient events was 7.9% (N=911) with low-molecular-weight heparin therapy, as compared with 22.5% (N=666) with placebo (P<001).27

Eikelboom et al28 performed a separate meta-analysis and reported that in patients who received extended prophylaxis with heparin or warfarin after THR or TKR, the risk of symptomatic venous thromboembolism was reduced to approximately 20 symptomatic events per 1000 patients treated.28 Conversely, a meta-analysis of studies evaluating outcomes of 13,169 THR and TKR patients who received short-duration (7-10 days) anticoagulant prophylaxis after THR or TKR determined that they were still at significant risk for thromboembolism.29 The investigators extrapolated from these findings that, without extended prophylaxis, nonfatal venous thromboembolism will occur in approximately 1 of 32 patients and fatal pulmonary embolism will occur in approximately 1 of 1000 patients within 3 months of surgery.29

table

Surveillance

Surveillance testing with impedance plethysmography or duplex ultrasonography is another approach to nonpharmacologic prophylaxis. However, sonography tests are expensive and provide moderate sensitivity and positive predictive value when used in asymptomatic, high-risk patients, such as those undergoing major orthopedic surgery.7 In large studies of THR and TKR patients, the use of screening compression ultrasonography prior to hospital discharge was not associated with reduced rates of venous thromboembolism. Therefore, use of this test to screen for deep vein thrombosis cannot be justified clinically.30,31

Conclusion

Reducing the risk of thromboembolism in patients who undergo hip and knee procedures continues to be an important clinical focus among orthopedic surgeons. Although prophylaxis has gained widespread acceptance in recent years, the risks and benefits of specific modalities and regimens deserve consideration. Although the emphasis of this report is on current clinical recommendations of the American College of Chest Physicians and evidence-based clinical practice, it is recognized that other factors, such as cost, convenience, ease and safety of administration, bleeding, and thrombosis risk, also play a part in individual decisions surrounding the choice and duration of prophylaxis. Orthopedic surgeons should take note that their input will play a major role in the 2003 recommendations of the American College of Chest Physicians panel that will formulate the next iteration of prophylactic guidelines.

References

  1. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001; 119:132-175.
  2. Ridker PM. Inherited risk factors for venous thromboembolism: implications for clinical practice. Clin Cornerstone. 2000; 2:1-14.
  3. Caprini JA, Arcelus J, Sehgal LR, et al. The use of low-molecular-weight heparins for the prevention of postoperative venous thromboembolism in general surgery. A survey of practice in the United States. Int Angiol. 2002; 21:78-85.
  4. Brookenthal KR, Freedman KB, Lotke PA, Fitzgerald RH, Lonner JH. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty. 2001; 16:293-300.
  5. Colwell CW Jr. Low-molecular-weight heparin prophylaxis in total knee arthroplasty: the answer. Clin Orthop. 2001; 392:245-248.
  6. Clagett GP, Anderson FA, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995; 108:312-334.
  7. Dalen JE, Paraskos JA, Ockene IS, Alpert JS, Hirsh J. Venous thromboembolism: scope of the problem. Chest.1986; 89:370-373.
  8. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Quick reference guide for clinicians. Available at: http://www.chestnet.org/guidelines/antithrombotic/index.php.
  9. Mesko JW, Brand RA, Iorio R, et al. Venous thromboembolic disease management patterns in total hip arthroplasty and total knee arthroplasty patients. A survey of the AAHKS membership. J Arthroplasty. 2001; 16:679-688.
  10. Groce JB, III. Treatment of deep vein thrombosis using low-molecular-weight heparins. Am Jn Care. 2001; 7:510-523.
  11. Bottner F, Sculco TP. Nonpharmacologic thromboembolic prophylaxis in total knee arthroplasty. Clin Orthop. 2001; 392:249-256.
  12. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996; 334:677-681.
  13. Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med. 1996; 334:682-687.
  14. Harrison L, McGinnis J, Crowther M, Ginsberg J, Hirsh J. Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin. Arch Intern Med. 1998; 158:2001-2003.
  15. Spyropoulos AC. Outpatient-based treatment protocols in the management of venous thromboembolic disease. Am J Managed Care. 2000; 6:1034-1044.
  16. Colwell CW Jr, Collis DK, Paulson R, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 1999; 81:932-940.
  17. Hull R, Raskob G, Pineo G, et al. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med. 1993; 329:1370-1376.
  18. RD Heparin Arthroplasty Group. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg Am. 1994; 76:1174-1185.
  19. Francis CW, Pellegrini VD Jr, Totterman S, et al. Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin. J Bone Joint Surg Am. 1997; 79:1365-1372.
  20. Hull RD, Pineo GF, Francis C, et al. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med. 2000;160:2199-2207.
  21. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000; 355:1295-1302.
  22. Bauer KA, Eriksson BI, Lassen MR, Turpie AG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001; 345:1305-1310.
  23. 23. Sanofi-Synthelabo, Arixtra Prescribing Information. Available at: http://www.sanofi-synthelabous.com/products/index.html#. Accessed October 16, 2002.
  24. Hopfner R. Ximelagatran (AstraZeneca). Curr Opin Investig Drugs. 2002; 3:246-251.
  25. Strebel N, Prins M, Agnelli G, Buller HR. Preoperative or postoperative start of prophylaxis for venous thromboembolism with low-molecular-weight heparin in elective hip surgery? Arch Intern Med. 2002; 162:1451-1456.
  26. Agnelli G, Mancini GB, Biagini D. The rationale for long-term prophylaxis of venous thromboembolism. Orthopedics. 2000; 23:643-646.
  27. Hull RD, Pineo GF, Stein PD, et al. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med. 2001; 135:858-869.
  28. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet. 2001; 358:9-15.
  29. Douketis JD, Eikelboom JW, Quinlan DJ, Willan AR, Crowther MA. 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.
  30. Robinson KS, Anderson DR, Gross M, et al. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: The Post-Arthroplasty Screening Study. A randomized, controlled trial. Ann Intern Med. 1997; 127:439-445.
  31. Leclerc JR, Gent M, Hirsh J, Geerts WH, Ginsberg JS. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Canadian Collaborative Group. Arch Intern Med. 1998; 158:873-878.

Authors

From the Scripps Clinic, Torrey Pines, La Jolla, Calif.