Current issues in the management of Superficial Vein Thrombosis - SVT Athanasios D. Giannoukas MD, MSc(Lond.), PhD(Lond.), FEBVS Professor of Vascular Surgery Faculty of Medicine, School of Health Sciences, University of Thessalia, Greece Chairman, Dept. of Vascular Surgery, University Hospital of Larissa Larissa, Greece
DISCLOSURES Participation in CALISTO Trial sponsored by GLAXO Honoraria from BAYER and Leo
Are all SVTs the same?
NO
SVT and VVs Prevalence of SVT in pts with VVs: 4-59% GSV system involved in 60-80% SSV system involved in 10-20% Bilateral: 5-10% SVT more frequently confined to varicose tributaries Leon L, Giannoukas A, et al. Eur J Vasc Endovasc Surg 2005;29:10 17 Decousus H, et al. POST Study Group. Ann Intern Med 2010;152:218 224 Lutter KS, et al. Surgery 1991;100:42 46
SVT and VVs Obesity, age and PS deficiency have been found as factors associated with SVT episodes in patients with VVs Karathanos Ch, Sfyroeras G, Drakou A, Roussas N, Exarchou M, Kyriakou D, Giannoukas AD. Eur J Vasc Endovasc Surg 2012;43:355-8. Karathanos Ch, Exarchou M, Tsezou A, Kyriakou D, Wittens C, Giannoukas AD. Trhomb Res 2013;132:47-50 Other potential mechanisms: defect in fibrinolysis & PLT aggregation (further work is needed)
SVT without VVs 5-10% of all cases Saphenous trunk thrombosis denotes often a more significant thrombotic process Pts with SVT without VVs with GSV trunk involvement have high prevalence of hypercoagulable states (3.6-72%) or malignancy Arguably pts with spontaneous SVT without VVs, or when thrombosis is extending to the GSV main trunk should be screened for hypercoagulability and exclude malignancy
SVT without VVs In the absence of VVs, malignancy, and autoimmune diseases the risk of SVT was: 6-fold for factor V Leiden mutation 4-fold for factor II G20210A mutation 13-fold for anti-thrombin III, protein C & S deficiency Decousus H et al. Thrombosis Research 2011; 127 (3) 81 85 Decousus H et al. Curr Opin Pulm Med 2003;9:393 397 Belcaro G, Nicolaides AN, et al. Angiology 1999;50:523 529
GSV thrombosis in the thigh without VVs (no progression pancreatic cancer was discovered) Without compression With compression
Is imaging needed in the diagnostic approach?
Yes imaging in necessary Colour Flow Doppler Imaging
Diagnostic approach Poor correlation between clinical exam and surgical findings Gjores JE, Angiology 1962 Most of the literature recommends D/S for confirmation of diagnosis, SVT extension, DVT exclusion, and F-up
SVT & DVT Prevalence of DVT with SVT in the presence of VVs ranged 13% to 28.8% Skillman et al, J Vasc Surg 1990 Jorgensen et al, J Vasc Surg 1993 Galanaud et al. OPTIMEV study. Thromb Haemost 2011 POST study. J Vasc Surg 2012 SVT at GSVak and DVT: 17-19% SVT at GSVbk and DVT: 4-5% Gengelis et al, J Vasc Surg 1996 Bergqvist & Jaroszewski, BMJ 1986
SVT & DVT Factors that are associated with increased risk of concurrent DVT with SVT OPTIMEV study (Galanaud et al. Thromb Haemost 2011;105:31-9) Age >75 yrs Active cancer Inpatient status SVT on non-varicose veins 8% symptomatic VTE complications at 3 months PE 0.5% DVT 2.8% SVT extension 3.3% SVT recurrence 1.9% POST study (Ann Intern Med 2012;152:218) Age >75 yrs History of previous DVT or PE SVT on non-varicose veins 5/844 DVT in the other limb Do we need to scan the other limb?
Thrombosis extension to SFJ
Can SVT cause PE?
Can SVT cause PE? We do not know as there is no solid evidence from the literature
SVT & PE Most studies available included small number of patients Prevalence ranges from 1.5% to 33% Zollinger et al, Arch Surg 1962 Unno et al, Surg Today 2002 Verlato et al, J Vasc Surg 1999 Unclear whether PE associated with SVT arises from clot extended into the deep veins or from clot detachment when it is confined to superficial veins
Thrombosis extension to SFJ
Considerations in the management Are antibiotics needed? What is the role of aspirin and NSAIDs?
Considerations in the management No place for antibiotics unless in case of use of indwelling catheters The role of aspirin and NSAIDs orally or locally and hirudoid locally is not well defined. Mostly alleviate the pain and local inflammatory signs
Is Anticoagulation needed?
Guidelines (ACCP - International Consensus) Fondaparinux 2.5 mg daily for at least 4 weeks is an effective treatment (Grade 1b)
2010;363:1222 1232
Considerations in the management CALISTO study The primary efficacy outcome (death from any cause or symptomatic PE, symptomatic DVT, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of DVT at day 47) occurred in 0.9% of patients in the fondaparinux group and 5.9% in the placebo group (P < 0.001). The rate of PE or DVT was 85% lower in the fondaparinux group. Similar risk reductions were observed at day 77. No difference was observed in major bleeding between the two groups. Decousus H et al. CALISTO Study Group. N Engl J Med 2010;363:1222 1232
Is this evidence convincing?
Goldman and Ginsberg. NEJM 2010;363:1278 Historical comparisons have shown extremely low mortality among untreated pts with SVT, which supports an initial no anticoagulation treatment approach unless conservative measures fail to resolve symptoms or DVT develops Treatment with Fondaparinux for 45 days may be reasonable in case of severe symptoms, thrombosis in the proximal saphenous vein, or in recurrent disease Cost-effectiveness issues Therapy with Fondaparinux 2.5 mg daily for 45 days costs $2,124 to $7,380 Giannoukas AD et al. The SeVEN study Phlebology 2017 In about a third of patients treatment with Tinzaparin 0.5 ml (10,000 ui) for 16 days sufficed while the remaining 2/3 needed treatment for 37 days
3-month incidence of symptomatic VTE (%) CALISTO in Real-world practice 5.0 5 4,5 4.5 4.0 4 3,5 3.5 3.0 3 2,5 2.5 2.0 2 1,5 1.5 1.0 1 0,5 0.5 0 p=0.06 DVT or PE DVT PE Patients that could have been included in CALISTO Patients that would not have been included in CALISTO Décousus H, Leizorovicz A, Bauersachs R, et al: N Engl J Med 2010; 363: 1222-1232 Galanaud JP, J Thromb Haemost 2012; 10: 1004-11. Galanaud JP. The OPTIMEV study. Thromb Haemost 2011; 105: 31-9.
Guidelines (ACCP - International Consensus) LMWH in intermediate doses for at least one month is recommended (Grade 2a )
STEFLUX trial Superficial ThromboEmbolism and Fluxum: A randomized double-blind study of low-molecular-weight heparin (parnaparin) for superficial vein thrombosis 664 outpatients with SVT of the long or short saphenous vein or collateral veins that was at least 4 cm long Patients were randomly assigned to 1 of 3 different doses and durations of LMWH (parnaparin). The 30-day intermediate dose of LMWH was superior to either the 30-day prophylactic dose or the 10-day intermediate dose in reducing the primary outcome (a composite of symptomatic and asymptomatic DVT, symptomatic PE, and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 3 days) with 60-day follow-up. No increase in major bleeding occurred Cosmi B et al. J Thromb Haemost. 2012;10(6):1026-1035
SeVEN Study Tinzaparin in intermediate dose (0.5 ml, 10.000 Ant-Xa IU, once daily) was a safe approach for the treatment of Superficial Vein Thrombosis Almost 1/3 of patients required short term treatment (16.2 days) and 2/3 of them received treatment for a prolonged period (36.9 days) The localization of thrombosis (above the knee) and poor mobilization were factors accompanied by prolonged treatment Thrombotic events recurrence was independent of the duration of treatment, and there was a tendency to increase in the presence of venous valvular insufficiency/varicose veins in the extremity Giannoukas et al. Phlebology 2017 31
Conclusion Extended 3-month treatment with Tinzaparin in intermediate doses was more effective in terms of VTE recurrence as compared to 2-month treatment with variable Tinzaparin dose (0% vs. 15.3%, p=0.004) Clinically extensive SVT was an independent factor for recurrence Predictors for DVT/PE were clinically extensive SVT, absence of local pain, US findings of axial trunk thrombosis, and multiple sites of SVT. Nikolakopoulos et al. Vasc Spesialist Int 2018 32
Is this evidence enough?
Probably YES But more well designed studies would help to define the duration of treatment in respect to the SVT thrombotic burden
Bear in mind that Clinical trials have included intermediate-risk SVT patients and have excluded those with small and high thrombotic burden The most appropriate treatment for patients who have SVT with a small thrombotic burden (thrombus length <4-5 cm and location >3 cm from the SFJ or SPJ) may be considered the use of topical or oral NSAID for 8 to 12 days The most appropriate treatment for patients who have high-risk SVT (thrombus location <3 cm from the SFJ and possibly from the SPJ) is therapeutic anticoagulation with vitamin K antagonists or possibly direct oral anticoagulants for 3 months Cosmi B. Management of superficial vein thrombosis. J Thromb Haemost 2015;13(7):1175-1183 Patients who have intermediate-risk SVT (thrombus length >4-5 cm and location >3 cm from the SFJ or SPJ) should receive 2.5 mg of fondaparinux once daily for 45 days, or else intermediate-dose LMWH for 4 to 6 weeks Décousus H, Bertoletti L, Frappé P. J Thromb Haemost. 2015;13(suppl 1):S230-S237
What is the role of surgery?
Surgery for SVT Surgical treatment with elastic stockings was associated with lower VTE rate and SVT progression compared to elastic stockings alone DiNisio M, Wichers IM, Middeldorp S. Cochrane Database Syst Rev 2008;3;00075320-100000000-0401 A review of six studies comparing surgical therapy to anticoagulation showed that surgery was superior in rapid symptom relief, but was associated with higher incidence of VTE and complications Sullivan V et al. J Am Coll Surg 2001;193:556-562
SVT on a varicose GSV close to SFJ GSV SFJ SFJ ligation and proximal thrombosed GSV excision
Thanks for the attention