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Letters to the Editor
Table 2. Incidence of post-thrombotic syndrome in patients according to the use of compression elastic stockings and the presence of resid- ual vein thrombosis and poplitieal valve reflux.
PTS No RVT and/or PVR RVT and/or PVR PVR alone RVT alone RVT and PVR NoECS ECS NoECS ECS NoECS ECS NoECS ECS NoECS ECS
(N=139)
Mildandsevere 42 (30.2)
(N=183) (N=211)
48 135 (26.2) (64.0)
(N=328) (N=35)
114 10 (34.8) (28.6)
(N=80)
18 (22.5)
(N=103)
70 (68.0)
(N=196)
68 (34.7)
(N=73)
55 (75.3)
(N=52)
28 (53.8)
0.430
Severealone 6 5 19 14 2 3 9 9 8 2
P
P
(4.3)
(2.7) (9.0)
0.001
0.001
(4.3) (5.7)
0.488 0.763
(3.8) (8.7)
0.001
0.001
0.001
(4.6) (11.0) (3.8)
0.028
0.625
PTS: post-thrombotic syndrome; RVT: residual vein thrombosis; PVR: popliteal valve reflux; ECS: elastic compression stockings. Numbers in brackets are percentages.
Recently, a hypothesis-generating meta-analysis showed a more than two-fold higher incidence of PTS in patients with ultrasound evidence of RVT at least 6 weeks after the index DVT.9 In patients with PVR, the incidence of PTS was also increased but only by one- third. In hindsight, this small increase could be easily explained by the confounding effect of RVT, which can also occur in combination with PVR. Indeed, in our study 48% of patients with PVR also had RVT, but in the mul- tivariate minimal-significant Cox model, there was no independent effect of PVR on the incidence of PTS, or on the relative efficacy of adequate use of ECS.
Our observation is pathophysiologically plausible. Indeed, in the absence of longstanding vascular damage, venous hypertension and subsequently PTS are unlikely to occur.9,14 This is also consistent with the demonstra- tion that PTS is unlikely to develop in individuals with a limited thrombotic burden and in those with isolated calf DVT.1
Our results are robust, as they are based on a prospec- tive observation of patients with proximal DVT who were followed up for as long as 3 years.11 Furthermore, the assessment of the adequacy of use of ECS was done by physicians who were unaware of clinical outcomes or potential confounders. To minimize the effect of poten- tial confounders, patients with recent ipsilateral DVT were excluded, as were patients with a short life expectancy and those requiring indefinite anticoagula- tion. The main limitation of our study was the lack of random allocation to ECS or no ECS. However, the two study groups were virtually comparable for demographic and clinical characteristics.
The clinical implication of our observations in combi- nation with results of contemporary studies is that in patients without RVT at 3 months, ECS can be safely withheld as long as leg complaints have disappeared, ide- ally after completing the first 6 months following the thrombotic episode.15 However, there is still uncertainty regarding patients with substantial damage to their venous system, as demonstrated by the presence of RVT at 3 months. Hence, we believe that trials should be ini- tiated to assess the effect of ECS in patients with proxi- mal DVT and RVT. As our patients were instructed to use ECS from the beginning, and the likelihood of RVT at 3 months was substantial (>50%), we think that both in clinical practice and in further confirmatory studies ECS should be given as soon as possible after the acute DVT to all patients while awaiting the ultrasound test, which has the potential to help decisions on the subsequent approach.
In conclusion, our results show that the ultrasound assessment of RVT in patients with proximal DVT has
the potential to identify those who are likely to benefit from the long-term use of ECS. While awaiting confirma- tion from properly randomized clinical trials, they are, in our opinion, plausible enough to inform the long-term management of patients with proximal DVT.
Paolo Prandoni,1 Anthonie W.A. Lensing,1 Martin H. Prins,2 Sabina Villalta,3 Raffaele Pesavento,4 Daniela Tormene,5 Franco Noventa6 and Gualtiero Palareti1
1Arianna Foundation on Anticoagulation, Bologna, Italy; 2Department of Clinical Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands; 3Division of Internal Medicine, Civic Hospital of Castelfranco Veneto, Italy; 4Division of Internal Medicine, Civic Hospital of Montebelluna, Italy; 5Department of Medicine, University Hospital of Padua, Italy and 6Department of Molecular Medicine, University of Padua, Italy
Correspondence:
PAOLO PRANDONI - prandonip@gmail.com doi:10.3324/haematol.2021.279680
Received: July 21, 2021.
Accepted: September 1, 2021.
Pre-published: September 9, 2021.
Disclosures: no conflicts of interest to disclose.
Contributions: PP, AWAL and MHP designed the study; SV, RP and DT contributed patients, and analyzed and interpreted data; FN and MHP performed the statistical analysis; GP provided the administrative support; PP, AWAL and MHP drafted the manuscript; all authors critically wrote or revised the intellectual content of the manuscript, reviewed and/or commented on each draft, and approved the final version for submission.
References
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2. Subbiah R, Aggarwal V, Zhao H, Kolluri R, Chatterjee S, Bashir R. Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials. Lancet Haematol. 2016;3(6):e293-300.
3. Brandjes DP, Büller HR, Heijboer H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal- vein thrombosis. Lancet. 1997;349(9054):759-762.
4. Prandoni P, Lensing AW, Prins MH, et al. Below-knee elastic com- pression stockings to prevent the post-thrombotic syndrome: a ran- domized, controlled trial. Ann Intern Med. 2004;141(4):249-256.
5. Mol GC, van de Ree MA, Klok FA, et al. One versus two years of elastic compression stockings for prevention of post-thrombotic syn- drome (OCTAVIA study): randomised controlled trial. BMJ. 2016;353:i2691.
6. Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to pre- vent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014;383(9920):880-888.
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