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Superficial Venous Thrombophlebitis: To Treat or Not To Treat - Evidence Behind the 2008 ACCP Recommendations

Superficial Venous Thrombophlebitis: To Treat or Not To Treat - Evidence Behind the 2008 ACCP Recommendations. Nathan Wanner, M.D. Clinical Instructor Thrombosis Service Associate Physician. Definitions.

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Superficial Venous Thrombophlebitis: To Treat or Not To Treat - Evidence Behind the 2008 ACCP Recommendations

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  1. Superficial Venous Thrombophlebitis: To Treat or Not To Treat - Evidence Behind the 2008 ACCP Recommendations Nathan Wanner, M.D. Clinical Instructor Thrombosis Service Associate Physician

  2. Definitions • Superficial phlebitis or superficial thrombophlebitis – inflammation of superficial vein ± thrombosis • Infusion thrombophlebitis – catheter or blood draw • Varicose vein thrombosis – thrombosis involving dilated, tortuous vein usually in SQ tissue of leg • Superficial vein thrombosis (SVT) • Suppurative (septic) thrombophlebitis • Misnomer – superficial femoral vein • Eponyms • Mondor’s disease – thrombophlebitis involving the breast or the dorsal penile vein • Trousseau’s syndrome – migratory thrombophlebitis associated with malignancy, particularly adenocarcinoma of the pancreas

  3. Anatomy – Upper Extremity Superficial Phlebitis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2009

  4. Anatomy – Lower Extremity Deep Veins Superficial Phlebitis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2009

  5. Anatomy – LE Superficial Veins Superficial Phlebitis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2009

  6. Clinical Features • Clinical manifestations • Erythema • Pain/tenderness • Edema • Palpable cord • Diagnosis • Clinical • Venous duplex

  7. Beyond “Superficial Thrombophlebitis” • Infusion thrombophlebitis • Varicose vein (VV) thrombosis • Superficial vein thrombosis • Above the knee • Below the knee

  8. Infusion Thrombophlebitis • Primarily an inflammatory process (vs. thrombotic) • Incidence up to 20-25% with inpatients with PIV • Causes • Physical trauma • Chemical irritation • Thrombosis • Infection • Diagnosis • Clinical • Venous duplex • Develops quickly and spontaneously resolves in days to weeks Arch Intern Med 1998;158(2):151-6. Am J Med 2002; 113:146–151

  9. Infusion Thrombophlebitis - Treatment • Heparin gel vs. placebo – 126 inpatients • Resolution at 7 days in 44% with heparin vs. 26% with placebo • Topical diclofenac vs. systemic diclofenac vs. placebo • Positive response 60% in both treatment groups vs. 20% with placebo at 48 hours • Heparinoid cream vs. piroxicam gel vs. placebo – 68 pts with infusion-related or spontaneous thrombophlebitis • No difference in symptoms at 14 days • Topical essaven gel vs. placebo – 23 pts • Significant improvement in symptoms with gel • No controlled trials evaluating systemic anticoagulation Med Clin (Barc) 2000;114:371–373. Eur J Clin Pharmacol 1999;54:917–921. Ann Chir Gynaecol 1990; 79:92–96. Angiology 2001; 52(S3):S63–S67

  10. Infusion Thrombophlebitis – ACCP 2008 Guidelines • Symptomatic infusion thrombophlebitis: • Oral diclofenac or another NSAID (Grade 2B), OR • Topical diclofenac gel (Grade 2B), OR • Heparin gel (Grade 2B) • Until resolution of symptoms or for up to 2 weeks. • We recommend against the use of systemic anticoagulation (Grade 1C). Chest2008;133;454-545

  11. Varicose Vein Thrombosis • Background • VV found in 10-20 percent of men and 25-33 percent of women • Pathophysiology – valve reflux • Risk factors • Prolonged standing • Pregancy, constipation, obesity, chronic cough, tumor • Congenital • Deep venous thrombosis • Diagnosis of thrombosis • Clinical • Venous duplex • Natural history - benign • Treatment – conservative vs. surgical • Surgery generally done for cosmetic or symptomatic reasons Am Fam Physician. 2008;78(11):1289-1294

  12. Superficial Vein Thrombosis - Background • Primarily a thrombotic process (vs. inflammatory) • Incidence may be greater than that of DVT • Risk factors • Varicose veins • Sclerotherapy • Catheters, infusions, infections • Venous insufficiency • Hypercoagulable states • Malignancy • Autoimmune disorders • Hormonal therapy/pregnancy • Obesity • Surgery and trauma • History of VTE Chest2008;133;454-545

  13. SVT and Hypercoagulability • Association with hypercoagulable state in absence of varicose veins, autoimmune disease, malignancy • Factor V Leiden OR = 6 • Prothrombin mutation OR = 4 • Deficiency of AT, prot C, prot S OR = 13 • Anticardiolipin Ab associated with recurrent SVT • Multiple small studies suggest an association between hypercoagulable states and SVT, especially when the saphenous trunk is involved Thromb Haemost 1999;82:1215. Eur J Vasc Endovasc Surg 2005;29:10. Angiol 2001:52:127

  14. SVT and Malignancy • Literature review looking at vascular disorders preceding a diagnosis of cancer found an association between STP and malignancy suggesting a causal link • SVT involving the legs in 106 limbs • Malignancy in 14 cases (13%) • 3 of the 14 cancers were diagnosed after SVT • SVT involving GSV or LSV in 398 pts • Ascending thrombosis in 56 • 10 of these (18%) had malignancy Angiology 2003;54:11. Phlebologie 1993;46:633. Vasa 1998;27:34.

  15. Natural History (Flowchart) SVT Extension Resolution Pulmonary embolism Ongoing resolution Resolution Recurrence

  16. SVT Association with VTE • 6-53% coexistence with DVT • 2.6-15% propagation to DVT • 20-33% coexistence with asymptomatic PE • 2-13% symptomatic PE Eur J Vasc Endovasc Surg 2005;29:10-17. Cochrane Database of Systematic. Reviews 2007;Issue 2:Art #CDOO4982

  17. SVT Treatment Options • Mechanical treatment • Topical treatments (heparin, NSAIDS) • Systemic NSAIDs • Anticoagulants • Surgery (ligation ± stripping)

  18. Superficial Thrombophlebitis – Treatment • Unblinded RCT involving patients with LE SVT associated with varicose veins • 6 treatment arms with ~70 patients each: • Compression • Ligation • Ligation with stripping • Low-dose UFH • LMWH • Warfarin • Low quality study – high dropout rate, unclear dosing and duration of anticoagulation • Anticoagulation decreased extension of STP compared with compression alone or venous ligation • No statistically significant difference in rate of DVT (~3-8%) • One third of DVT events were in the contralateral leg Angiology 1999;50:523-529

  19. STENOX Trial 2003 • Double-blind RCT in pts with LE SVT(~100 pts/group) • 8-12 days of therapy then venous duplex U/S followup Arch Int Med 2003;163:1657-1663

  20. Low- vs. High-Dose Heparin • Unblinded RCT comparing low- vs. high-dose SQ UFH for above-knee GSV thrombosis in 60 patients • High-dose = 12,500 bid for 1 week then 10,000 bid • Low-dose = 5000 bid • Venous duplex U/S on days 3, 7, 30, and 90 • Treated 4 weeks and followed 6 months • VTE rate 20% in low-dose vs. 3.3% for high-dose (p=0.05) Haematologica 2002;87:523-527

  21. Prophylactic vs. Therapeutic LMWH - The Vesalio Investigators Group • Double-blind RCT involving 164 patients with GSV thrombosis • Randomized to prophylactic vs. therapeutic (full dose for 1 week then half dose) nadroparin • Treated for 1 month then followed for 3 months • Venous duplex U/S at days 3, 7, 30, and 90 • SVT extension or VTE • 8.6% in low-dose group (5 of 7 within first month) • 7.2% in high-dose group (2 of 6 within first month) • P=0.74 J Thromb Haemost 2005;3:1152-1157

  22. Medical vs. Surgical Treatment • Systematic review including 6 studies of above-knee SVT • Extension to DVT in 3.4% of surgical vs. 2.2% medical patients • PE in 2 surgical patients (2%) vs. no medical pts • Surgical complication rate 7.7% • RCT involving 84 pts with SVT – ligation vs. 4 weeks of enoxaparin (1mg/kg bid for first week then 1mg/kg daily) • Surgical group • Complications 6.7% • Recurrence of SVT 3.3% • PE 6.7% • Medical group • Minor bleeding 6.7% • Recurrence of SVT 10% • No DVT or PE • Savings of >$1000 per pt vs. surgery Angiology 1999;50:523-529. Vasc Endovasc Surg 2003;37:415-420. J Am Coll Surg 2001;193:556-562.

  23. NSAIDS in Addition to LMWH For Symptom Management? • 50 pts with SVT involving the GSV randomized to therapeutic nadroparin (190 anti-Xa IU/kg qd) OR nadroparin and acemetacine 60mg bid • Duration of treatment 10 days • No major complications in either group • Significant reduction in pain and local tenderness with acemetacine Phlebology 2009;24(2):56-60

  24. SVT - ACCP 2008 Guidelines • Spontaneous superficial vein thrombosis: • Prophylactic or intermediate doses of LMWH (Grade 2B) OR • Intermediate doses of UFH (Grade 2B) • At least 4 weeks • As an alternative, VKA (target INR, 2.5; range, 2.0 to 3.0) can be overlapped with 5 days of UFH and LMWH and continued for 4 weeks (Grade 2C) • Oral NSAIDs should not be used in addition to anticoagulation (Grade 2B) • We recommend medical treatment with anticoagulants over surgical treatment (Grade 1B) • It is likely that less extensive superficial vein thrombosis (ie, where the affected venous segment is short in length or further from the saphenofemoral junction) does not require treatment with anticoagulants Chest 2008; 133:454S–545S

  25. Take Home Points • Infusion thrombophlebitis and varicose vein thrombosis are generally benign and do not require systemic treatment • Superficial venous thrombosis near the saphenofemoral junction has a significant risk of extension or recurrence • Systemic anticoagulants are generally indicated and are preferred over surgical treatment • Duration of therapy should probably be at least 4 weeks • Optimal dosing is unclear

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