77 – How should patients with post-operative proximal (popliteal or supra-popliteal) DVT be managed?

Andrew J. Hughes, Emanuele Chisari, Javad Parvizi.

Response/Recommendation: In line with the current guidelines, we recommend that consideration should be given to treat proximal deep venous thrombosis (DVT), affecting popliteal or suprapopliteal vessels, arising acutely in patients undergoing orthopaedic procedures.

Strength of Recommendation: Moderate.

Rationale: Venous thromboembolism (VTE) is a well-recognized complication following lower limb orthopaedic surgery1,2. Peak onset of DVT is within postoperative weeks two and three3,4, with the risk remaining elevated for 6 – 12 weeks, falling gradually thereafter until 4 – 6 months postoperatively5-8. Asymptomatic proximal DVT, affecting popliteal and suprapopliteal vessels, have been reported to constitute 27% of all DVT occurring following total hip arthroplasty (THA), and 15% of all DVT post total knee arthroplasty (TKA)9,10. Unprovoked proximal DVT are a cause for concern given their tendency to firstly recur11-16, and secondly to have a higher potential to propagate and cause pulmonary embolus (PE)11-16. Although such causal relationship for patients undergoing orthopaedic procedures has not been proven17-19. Relating to unprovoked DVT, consensus exists amongst the published guidelines stipulating that proximal DVT should be treated to avoid progression and prevent potential fatal PE. A causal relationship between the provoked postoperative DVT and PE has yet to be clearly demonstrated in the orthopaedic setting, however despite the serious risks associated with administration of anticoagulation, treatment is currently recommended within the published guidelines, whilst awaiting clarification by way of formal investigation5,19-22.

There are, however, guidelines by various organizations related to this subject matter. The American College of Chest Physicians (ACCP), the European Society of Cardiology (ESC), and the American Society of Hematology (ASH) suggest that acute postoperative proximal DVT should be treated with an anticoagulation agent, preferably a direct oral anticoagulant (DOAC)20,23-25. The guidelines also stipulate that some DOAC, namely dabigatran and edoxaban, should be administered after 5 – 10 days of parenteral low-molecular-weight heparin (LMWH)20,24,25. The ACCP suggests that a vitamin K antagonist should be favored as second-line over that of LMWH therapy, following appropriate bridging, with a recommended international normalized ratio (INR) target of 2.0 to 3.0 for the duration of treatment5,24-26. In patients with active cancer, and a confirmed acute postoperative DVT, the ACCP and ESC suggest LMWH as the first line given its favorable profile in reducing recurrent episodes of VTE in such patients20,24,27.

The above guidelines recommend that the anticoagulation should be continued for three months5,20,24,25. The decision for extended treatment beyond three months must be based on the risk-benefit ratio for each individual patient20.

Regarding the suspected postoperative DVT, patients post lower limb orthopaedic surgery almost certainly attain a Well’s score of at least 2, until the twelfth postoperative week. The published guidelines suggest commencing treatment with parenteral anticoagulation in situations where a diagnostic Doppler ultrasound may be delayed longer than 4 hours5,20,28. Current healthcare services cannot guarantee a Doppler ultrasound within this timeframe, most notably when patients present acutely over a weekend. Given the heightened risks of anticoagulation-associated hematoma, wound drainage, and surgical site infection (SSI) in the perioperative setting, orthopaedic surgeons have reservations about commencing therapeutic anticoagulation before confirming the diagnosis19-22. Perhaps, in the setting of a suspected DVT, when a Doppler cannot be performed within 4 hours, patients post lower limb orthopaedic surgery should continue on their VTE prophylaxis regimen, unless considered to be of significantly high risk by way of a history of thrombophilia or active cancer, in advance of organizing an urgent scan the next day.

Anticoagulation is suggested in favor of catheter-directed thrombolysis, systemic thrombolysis, and operative venous thrombectomy, in the setting of non-limb-threatening acute postoperative proximal DVT5,20,24,25,29,30. Adjuvant catheter-directed thrombolysis may be considered in patients with acute iliofemoral disease, with symptoms less than 14 days, and a life expectancy greater than 1 year20. Inferior vena cava (IVC) filters are suggested only for patients with contraindications to anticoagulation therapy, and routine use of IVC filter in addition to anticoagulation is not recommended5,24,25,31-34. Ambulation is recommended, although severe pain and swelling may require deferral5,20. Compression stockings are not routinely recommended in the setting of an acute provoked postoperative proximal DVT, unless providing symptomatic relief, as the literature has not proven any benefit in preventing the onset of post-thrombotic syndrome20,24,25.

Whilst guidelines suggest anticoagulation therapy based on population characteristics, the optimal treatment choice for each individual must be ascertained, based on a careful risk assessment, incorporating the preferences of both the patient and their family, following informed consent and shared decision making.

References:

1.         Warren JA, Sundaram K, Anis HK, Kamath AF, Higuera CA, Piuzzi NS. Have Venous Thromboembolism Rates Decreased in Total Hip and Knee Arthroplasty? J Arthroplasty. 2020 Jan;35(1):259-64.

2.         Keller K, Hobohm L, Barco S, Schmidtmann I, Münzel T, Engelhardt M, et al. Venous thromboembolism in patients hospitalized for knee joint replacement surgery. Nature Sci Rep. 2020;10:22440.

3.         Sweetland S, Green J, Liu B, Berrington de González A, Canonico M, Reeves G, et al. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. BMJ. 2009 Dec 3;339:b4583.

4.         Kahn SR, Shivakumar S. What’s new in VTE risk and prevention in orthopedic surgery. Res Pract Thromb Haemost. 2020 Mar;4(3):366-76.

5.         Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Supply):7S-47S.

6.         Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15.

7.         Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98.

8.         Caron A, Depas N, Chazard E, Yelnik C, Jeanpierre E, Paris C, et al. Risk of Pulmonary Embolism More Than 6 Weeks After Surgery Among Cancer-Free Middle-aged Patients. JAMA Surg. 2019 Dec;154(12):1126-32.

9.         Ciccone 2nd WJ, Fox P, Neumyer M, Rubens D, Parrish WM, Pellegrini Jr VD. Ultrasound surveillance for asymptomatic deep venous thrombosis after total joint replacement. J Bone Joint Surg Am. 1998;80(8):1167-74.

10.       Ciccone 2nd WJ, Reid JS, Pellegrini Jr VD. The Role of Ultrasonography in Thromboembolic Disease Management in the Orthopaedic Patient. Iowa Orthop J. 1999;19:18-25.

11.       Masuda EM, Kessler DM, Kistner RL, Eklof B, Sato DT. The natural history of calf vein thrombosis: lysis of thrombi and development of reflux. J Vasc Surg. 1998;28:67-74.

12.       Kazmers A, Groehn H, Meeker C. Acute calf vein thrombosis: outcomes and implications. Am Surg 1999; 65: 1124–7. Am Surg. 1999;65(1124-7).

13.       Palareti G, Cosmi B, Lessiani G, Rodorigo G, Guazzaloca G, Brusi C, et al. Evolution of untreated calf deep vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010;104(1063-1070).

14.       Kearon C. Natural History of Venous Thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):122-30.

15.       Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121:1630-6.

16.       Baglin T, Douketis J, Tosetto A, Marcucci M, Cushman M, Kyrle P, et al. Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis. J Thromb Haemost. 2010;8:2436-342.

17.       Della Valle CJ, Steiger DJ, DiCesare PE. Duplex ultrasonography in patients suspected of postoperative pulmonary embolism following total joint arthroplasty. Am J Orthop. 2003;32(8):386-8.

18.       Westrich GH, Farrell C, Bono JV, Ranawat CS, Salvati EA, Sculco TP. The incidence of venous thromboembolism after total hip arthroplasty: a specific hypotensive epidural anesthesia protocol. J Arthroplasty. 1999;14(4):456-63.

19.       Parvizi J, Jacovides CL, Bican O, Purtill JJ, Sharkey PF, Hozack WJ, et al. Is Deep Vein Thrombosis a Good Proxy for Pulmonary Embolus? J Arthroplasty. 2010;25(No. 6 Suppl):138-44.

20.       Mazzolai L, Aboyans V, Ageno W, Agnelli G, Alatri A, Bauersachs R, et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J. 2018;39(47):4208-18.

21.       Galat DD, McGovern SC, Hanssen AD, Larson DR, Harrington JR, Clarke HD. Early return to surgery for evacuation of a postoperative hematoma after primary total knee arthroplasty. J Bone Joint Surg Am. 2008;90(11):2331-6.

22.       D’Apuzzo MR, Keller TC, Novicoff WM, Browne JA. CT Pulmonary Angiography After Total Joint Arthroplasty: Overdiagnosis and Iatrogenic Harm? Clin Orthop Related Res. 2013;471(9):2737-42.

23.       Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e96S.

24.       Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic Therapy for VTE Disease – CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52.

25.       Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-738.

26.       Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS, et al. Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis. JAMA. 2014;312(11):1122-35.

27.       Carrier M, Cameron C, Delluc A, Castellucci L, Khorana AA, Lee AY. Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis. Thromb Res. 2014;134(6):1214-9.

28.       National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. NICE Guidelines. 2020:https://www.nice.org.uk/guidance/ng158/chapter/Recommendations – diagnosis-and-initial-management – accessed 24th October 2021.

29.       Haig Y, Enden T, Grotta O, Klow NE, Slagsvold CE, Ghanima W, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016;3:e64-e71.

30.       Garcia MJ, Lookstein R, Malhotra R, Amin A, Blitz LR, Leung DA, et al. Endovascular management of deep vein thrombosis with rheolytic thrombectomy: final report of the prospective multicenter PEARL (peripheral use of angiojet rheolytic thrombectomy with a variety of catheter lengths) registry. J Vasc Interv Radiol. 2015;26:777-85.

31.       Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e278S-e325S.

32.       Decousus H, A L, Parent F, Page Y, Tardy B, Girard P, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d’Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;338(7):409-15.

33.       The PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d’Embolie Pulmonaire par Interruption Cave) randomized study. Circulation. 2005;112(3):416-22.

34.       Mismetti P, Laporte S, Pellerin O, Ennezat PV, Couturaud F, Elias A, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA. 2015;313:1627-35.