July-August 2019, Volume 16, Issue 4
Superficial Thrombophlebitis: The Less Dangerous Cousin of Deep Vein Thrombosis That Can Still Cause Harm
Published on: May 22, 2019
Di Nisio M, Wichers I, Middeldorp S. Treatment of lower extremity superficial thrombophlebitis. JAMA. 2018;320:2367-2368.
Superficial thrombophlebitis (ST) is a painful thrombotic condition that presents as a tender, erythematous, palpable cord with localized edema. Unlike patients with acute deep vein thrombosis (DVT), patients with ST do not necessarily require anticoagulation. How then do we decide which patients require anticoagulant therapy? And if anticoagulants are recommended, which agent, dose, and duration should be prescribed?
The decision to prescribe anticoagulants for superficial thrombophlebitis is primarily based on the risk of progression into the deep venous system. Factors such as length of the ST (≥ 5 cm), proximity to junction with the deep veins (< 3 cm from saphenofemoral junction or perforator veins within the popliteal fossa), pregnancy, hormones, active inflammatory disease, prior venous thromboembolism (VTE) or ST, and active cancer increase the potential for progression. Patients without any of these risk factors can generally be treated with pain control measures (topical nonsteroidal anti-inflammatory drugs [NSAIDs] and compresses) in addition to clinical surveillance for worsening of symptoms. For patients with one or more of these risk factors, guidelines suggest anticoagulants be considered.1,2
To answer the question of which agent to use for treatment of ST, Dr. Marcello Di Nisio and colleagues recently published a clinical synopsis of their Cochrane review.3 Randomized controlled trials evaluating low-molecular-weight heparin (LMWH), fondaparinux, rivaroxaban, heparin spray gel, tenoxicam, naproxen, graduated compression stockings, and saphenofemoral disconnection were included in the review. The primary outcome measure was symptomatic VTE. Secondary outcome measures included ST extension, progression or recurrence, and symptom control.
In brief, when compared with placebo, only fondaparinux reduced the risk of symptomatic VTE,4 whereas fondaparinux, LMWH, and NSAIDs all reduced the risk of ST extension (Table). The largest trial comparing two active treatments showed no difference between fondaparinux 2.5 mg daily and rivaroxaban 10 mg daily for symptomatic VTE or ST extension.5 There was insufficient evidence for all other treatments. Key limitations for the two largest trials included restriction of enrollment to low-risk patients in the fondaparinux versus placebo trial,4 and the small number of events in the rivaroxaban trial.5
The clinical synopsis by Dr. Di Nisio and colleagues shows that the jury is still out on the right agent to use for treatment of ST. Fondaparinux is the most promising to date, but it requires 45 days of costly injections for a 1 percent absolute risk reduction for VTE.
My personal approach to treating ST starts with a risk assessment (site and length of the ST; risk factors as mentioned previously) followed by an ultrasound to exclude DVT (unless an isolated short segment confined to a varicose vein below the knee). If the ST is larger than or equal to 5 cm long and/or within 3 cm of the saphenofemoral junction, I perform a risk assessment for bleeding. If the risk of bleeding is low, I recommend either fondaparinux or rivaroxaban for 45 days (for pregnant patients LMWH is a safe alternative). If the bleeding risk is high, I arrange for a repeat ultrasound within five to seven days to rule out progression into the deep veins.
For all patients, I recommend topical diclofenac four times daily because I find it offers better pain control than oral NSAIDs, with fewer adverse effects. Duration of treatment is continued beyond 45 days if pain continues, but it is not based on resolution of the palpable cord (which turns brown and is no longer tender) or of ultrasound abnormalities, which can persistent indefinitely. Lastly, I review the symptoms of VTE. Upper extremity superficial thrombophlebitis was not covered in the referenced Cochrane review, but my approach is similar though the requirement for anticoagulants in these patients is less common.
Summary of Placebo-Controlled Trials for Treatment of Superficial Thrombophlebitis
|Agent||Comparator||No. of Studies||Symptomatic VTE RR (95% CI)||Extension of ST RR (95% CI)||GRADE Quality of Evidence|
|Fondaparinux 2.5 mg sc daily × 45 d||Placebo||1 (n = 3,002)||0.15 (0.04-0.50)||0.08 (0.03-0.22)||Moderate|
|LMWH prophylactic dose × 8-12 d||Placebo||1 (n = 222)||1.22 (0.38-3.89)||0.44 (0.26-0.74)*||Low|
|LMWH therapeutic dose × 8-12 d||Placebo||1 (n = 222)||0.85 (0.23-3.06)||0.46 (0.27-0.77)*||Low|
|NSAIDs||Placebo||1 (n = 211)||0.91 (0.25-3.28)||0.46 (0.27-0.78)||Low|
Abbreviations: LMWH, low-molecular-weight heparin; RR, relative risk; sc, subcutaneously; VTE, venous thromboembolism. *Also included recurrent superficial thrombophlebitis.
Kearon C, Akl EA, Comerota AJ, 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;141:e419S-e496S.
Superficial thrombophlebitis, superficial vein thrombosis. Thrombosis Canada Clinical Guideline. 2019.
Di Nisio M, Wichers IM, Middeldorp S. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev. 2018;2:CD004982.
Decousus H, Prandoni P, Mismetti P, et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med. 2010;363:1222-1232.
Beyer-Westendorf J, Schellong SM, Gerlach H, et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol. 2017;4:e105-e113.
Conflict of Interests
Dr. Linkins has received payment for data adjudication of the MARINER trial (rivaroxaban for prophylaxis in medical patients).
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