76 – How should patients with post-operative distal DVT be managed?

Karan Goswami, Brendan Gleason, Gregg R. Klein, William J. Hozack.

Response/Recommendation: In the absence of concrete evidence, the opinion of this workgroup is that patients with isolated distal deep venous thrombosis (DVT), can be monitored without treatment or treated by aspirin (ASA).

Strength of Recommendation: Limited.

Rationale: It is commonly accepted that patients with a postoperative proximal DVT (at or above the popliteal vein) or pulmonary embolism (PE) need to be anticoagulated^1,2. It is not, however, known if patients with a distal DVT (infrapopliteal) need to be treated or merely monitored for progression.

The main concern with the presence of DVT is that the emboli may mechanically propagate to the proximal veins and pulmonary vasculature, resulting in pulmonary dysfunction and possible fatal outcome¹. Based on older literature, the rate of progression of DVT varies between 0 to 44%^2–4. Two recent systematic reviews of mixed nonsurgical and surgical patients demonstrated that around 9.0% of distal DVT were found to extend proximally^2,5. In a randomized controlled trial (RCT) of patients with symptomatic distal DVT presenting to the emergency room, Horner et al., found that the propagation including proximal DVT, and PE was 11% in the conservatively treated group versus 0% in the anticoagulated group⁶. Similarly, in their systematic review of mainly nonsurgical patients, Lim et al., concluded that the risk for recurrence of DVT (odds ratio [OR] 0.16, p=0.01) or the extension of the distal DVT in a proximal deep vein (OR 0.29; p<0.004) was higher when a no treatment approach was performed compared with treatment with an anticoagulant drug⁷. Of note, the anticoagulation regimens in the included studies were heterogeneous in nature, including a variable combination of intravenous heparin, coumadin, or low-molecular-weight heparin (LMWH) (dalteparin, enoxaparin, or nadroparin).

Other studies have suggested that isolated distal DVT present a low risk for causing PE and may be clinically insignificant. They also question the value of aggressive treatment and even the need for any treatment^8,9. Palareti et al., adopted a surveillance approach in 65 patients with distal DVT and mixed risk factors including active malignancy, immobilization, or major surgery⁸. Untreated isolated distal DVT had a clinically uneventful course at 3-month follow-up, with a 3.1% rate of DVT extension into the proximal veins. Fleck et al., retrospectively reviewed 102 patients diagnosed with distal DVT, of which only 33.3% had recently undergone surgery⁹. Despite most of their cohort being treated with anticoagulation, no cases of PE were seen in the treated versus untreated patients. Relatively high rates of new proximal DVT propagation were reported in their untreated patients with distal DVT (3/14; 21.4%), however the study population had significant comorbidities including active malignancy in approximately one-third of patients, thereby limiting generalizability to orthopaedic patients. Those who advocate for monitoring the patients with distal DVT rather than treatment, cite the perils of administration of anticoagulation drugs, such as bleeding, as a disincentive for treating these patients. Development of hematoma, persistent wound drainage, and subsequent periprosthetic joint infections have all been associated with administration of anticoagulation, with ASA posing the lowest risk^5,10–12.

The Cochrane Library recently collated a systematic review pertaining to management of distal DVT. Kirkilesis et al., evaluated 8 RCT involving both nonsurgical and surgical patients which included 1,239 participants with distal DVT who were randomized to treatment with anticoagulation with vitamin K antagonists or no anticoagulation⁵. There was no difference with respect to development of PE (relative risk [RR] 0.81, 95% confidence interval [CI] 0.18–3.59) between the treatment groups. The anticoagulation group showed a reduced risk of recurrent VTE (RR 0.34, 95% CI 0.15–0.77), which was defined as any DVT recurrence in the calf veins, or progression of DVT to proximal veins, or PE development within 3-months. Recurrence of local distal DVT and propagation to proximal veins was also reduced (RR 0.25, 95% CI 0.10–0.67). The authors also found that ≥3 months reduced the incidence of recurrent VTE to 5.8% as compared with 13.9% in participants treated only for 6 weeks. While there was no statistical difference in major bleeding between the groups, there was an increase in clinically relevant non-major bleeding events in the group treated with anticoagulants (RR 3.34, 95% CI 1.07–10.46).  Righini et al., conducted a randomized, double-blind, placebo-controlled trial of mainly nonsurgical patients examining treatment of symptomatic distal DVT using LMWH. They reported LMWH was no better than placebo in reducing the risk of proximal extension or VTE events (3% vs 5%, p=0.54) in low-risk patients with symptomatic calf DVT but increased the risk of bleeding (risk difference 4.1, 95% CI 0·4–9·2, p=0.025). Notably, this study was underpowered at publication due to early termination of enrollment¹³.

Multiple retrospective studies have also shown relatively low rates of propagation of distal DVT, regardless of treatment approach. Li et al., evaluated 310 consecutive patients after vascular surgery and found 33 with distal DVT¹⁴. These 33 patients were randomized into full dose or half dose anticoagulation with LMWH and no progression of DVT was reported in either group. Parisi et al., reported on 171 patients with distal DVT treated with LMWH and showed 2.9% of patients had propagation to the proximal veins¹⁵. It is important to mention that the majority of patients with propagation had a history of unprovoked DVT in this study. More recently, Tsuda et al., followed 742 consecutive patients after THA with postoperative Duplex imaging¹⁶. The incidence of postoperative DVT was 33%. All the postoperative distal DVT that occurred in the calf veins (n=232) were not treated and remained benign postoperatively, with no cases of progression to the proximal veins seen during follow-up, and furthermore, 93% of distal DVT disappeared on serial imaging.

ASA is well studied as an effective VTE prophylaxis following total joint arthroplasty (TJA)¹⁷, yet its efficacy as an antithrombotic therapy following TJA is less clear in the orthopaedic patient. Becattini et al., showed a 42% reduction in the incidence of recurrent DVT in a multicenter randomized double-blind clinical trial of 402 nonsurgical patients with prior unprovoked VTE when prophylaxis with ASA was compared to placebo¹⁸. In another study, Brighton et al., also showed that low-dose ASA was effective in preventing recurrent VTE (hazard ratio [HR] 0.66, p=0.01) in a randomized placebo-controlled trial of 822 nonsurgical patients following their first episode of unprovoked VTE¹⁹. Omari et al., retrospectively reported on 486 patients with distal DVT after TKA who were treated with ASA 325mg twice daily²⁰. Follow-up doppler ultrasound was performed on 459/486 cases (94.4%) and demonstrated resolution of distal DVT in 445/459 (96.9%) cases. Doppler diagnosed propagation to a proximal vein occurred in 10/459 (2.2%) cases. One patient with a distal DVT developed a PE at 6 weeks postoperatively. The authors concluded that there was a low rate of distal DVT propagation in patients managed with ASA. Additionally, no significant bleeding episodes, wound-related complications, or other adverse events were noted from ASA therapy.

The majority of the literature evaluating treatment of distal DVT is in non-orthopaedic and non-surgical patients. These populations often include mixed diagnoses and levels of comorbidity, including malignancy, which continue to confound our understanding and provide limited evidence to guide management²¹. Distal DVT can either be treated immediately upon diagnosis (with anticoagulation) or be monitored (by holding anticoagulation and only treating progression to proximal veins or if PE is identified)⁵. Data suggesting that anticoagulation is indicated for distal DVT are limited, and such a strategy entails a risk of over-treatment when weighed against the risks of anticoagulation in the postoperative setting.

References:

1.         Wang C-J, Wang J-W, Weng L-H, Huang C-C, Yu P-C. Clinical significance of muscular deep-vein thrombosis after total knee arthroplasty. Chang Gung Med J. 2007;30(1):41-46.

2.         Garry J, Duke A, Labropoulos N. Systematic review of the complications following isolated calf deep vein thrombosis. Br J Surg. 2016;103(7):789-796. doi:10.1002/bjs.10152

3.         Righini M. Is it worth diagnosing and treating distal deep vein thrombosis? No. J Thromb Haemost JTH. 2007;5 Suppl 1:55-59. doi:10.1111/j.1538-7836.2007.02468.x

4.         Righini M, Paris S, Le Gal G, Laroche J-P, Perrier A, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost. 2006;95(1):56-64.

5.         Kirkilesis G, Kakkos SK, Bicknell C, Salim S, Kakavia K. Treatment of distal deep vein thrombosis. Cochrane Database Syst Rev. 2020;4:CD013422. doi:10.1002/14651858.CD013422.pub2

6.         Horner D, Hogg K, Body R, Nash MJ, Baglin T, Mackway-Jones K. The anticoagulation of calf thrombosis (ACT) project: results from the randomized controlled external pilot trial. Chest. 2014;146(6):1468-1477. doi:10.1378/chest.14-0235

7.         Lim MS, Ariyarajah A, Oldmeadow C, Hall A, Enjeti AK. A Systematic Review and Meta-analysis Comparing Anticoagulation versus No Anticoagulation and Shorter versus Longer duration of Anticoagulation for Treatment of Isolated Distal Deep Vein Thrombosis. Semin Thromb Hemost. 2017;43(8):836-848. doi:10.1055/s-0037-1604085

8.         Palareti G, Cosmi B, Lessiani G, et al. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010;104(5):1063-1070. doi:10.1160/TH10-06-0351

9.         Fleck D, Albadawi H, Wallace A, Knuttinen G, Naidu S, Oklu R. Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns. Cardiovasc Diagn Ther. 2017;7(Suppl 3):S134-S139. doi:10.21037/cdt.2017.11.03

10.       Sachs RA, Smith JH, Kuney M, Paxton L. Does anticoagulation do more harm than good?: A comparison of patients treated without prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty. J Arthroplasty. 2003;18(4):389-395. doi:10.1016/s0883-5403(03)00071-8

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13.       Righini M, Galanaud J-P, Guenneguez H, et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol. 2016;3(12):e556-e562. doi:10.1016/S2352-3026(16)30131-4

14.       Li Y, Ding J, Shen L, et al. Risk Factors and Anticoagulation Therapy in Patients With Isolated Distal Deep Vein Thrombosis in the Early Post-operative Period After Thoracic Surgery. Front Surg. 2021;8:671165. doi:10.3389/fsurg.2021.671165

15.       Parisi R, Visonà A, Camporese G, et al. Isolated distal deep vein thrombosis: efficacy and safety of a protocol of treatment. Treatment of Isolated Calf Thrombosis (TICT) Study. Int Angiol J Int Union Angiol. 2009;28(1):68-72.

16.       Tsuda K, Takao M, Kim J, Abe H, Nakamura N, Sugano N. Asymptomatic Deep Venous Thrombosis After Elective Hip Surgery Could Be Allowed to Remain in Place Without Thromboprophylaxis After a Minimum 2-Year Follow-Up. J Arthroplasty. 2020;35(2):563-568. doi:10.1016/j.arth.2019.08.062

17.       Azboy I, Barrack R, Thomas AM, Haddad FS, Parvizi J. Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: Commonly asked questions. Bone Jt J. 2017;99B(11):1420-1430. doi:10.1302/0301-620X.99B11.BJJ-2017-0337.R2

18.       Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366(21):1959-1967. doi:10.1056/NEJMoa1114238

19.       Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979-1987. doi:10.1056/NEJMoa1210384

20.       Omari AM, Parcells BW, Levine HB, Seidenstein A, Parvizi J, Klein GR. 2021 John N. Insall Award: Aspirin is effective in preventing propagation of infrapopliteal deep venous thrombosis following total knee arthroplasty. Bone Jt J. 2021;103-B(6 Supple A):18-22. doi:10.1302/0301-620X.103B6.BJJ-2020-2436.R1

21.       Robert-Ebadi H, Righini M. Should we diagnose and treat distal deep vein thrombosis? Hematol Am Soc Hematol Educ Program. 2017;2017(1):231-236. doi:10.1182/asheducation-2017.1.231