Prophylactic dose fondaparinux for 6 weeks in superficial thrombophlebitis of the legs reduces the risk for symptomatic thromboembolic complications
- 1Department of Medicine, Weill Cornell Medical Center, New York, New York, USA
- 2Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Correspondence to: Dr Maria T DeSancho
1305 York Avenue, 7th floor, New York, NY 10021, USA;
Superficial thrombophlebitis (ST), an inflammatory-thrombotic disorder in a superficial vein, is relatively common and estimated to occur in 1 per 1000 persons.1 The classic symptoms include pain, oedema, erythema and occasionally a palpable cord in the area of the thrombosed vein. Risk factors for ST include surgery, pregnancy and puerperium, female hormones, malignancy, infection, varicose veins, autoimmune disorders and thrombophilia.2 ST is a risk factor for deep venous thrombosis (DVT); 12–44% of patients with ST develop a DVT.3 The treatment of ST is highly variable ranging from no treatment to treatments with non-steroidal anti-inflammatory drugs, heparin gels and different regimens of anticoagulants and surgery.
This systematic review was undertaken to evaluate the safety and efficacy of the different treatment options for ST of the legs. The authors performed an extensive search of all relevant studies using electronic sources and reference lists of selected papers and haematology society conference proceedings. Only randomised controlled trials (RCTs) were included. Of note, there were only two new studies that were added since the last review in 2009.4 ,5
The primary outcome measures included the incidence of symptomatic DVT or pulmonary embolism (PE), progression of ST to DVT, asymptomatic or symptomatic extension or recurrence of ST, symptoms and signs of ST and quality of life. Standard diagnostic imaging studies were used to objectively document PE or DVT. Quality-of-life assessments were documented using disease-specific and non-specific questionnaires. Secondary outcomes included mortality, side effects of treatments and arterial thromboembolic events. The authors compared all treatments to improve local symptoms and signs and to prevent complications. Interestingly, neither the location of the affected superficial vein in the leg or patients’ age groups was specified in the Methods section. The authors decided not to use the GRADE methodology, because of the heterogeneity among the studies regarding treatment comparisons and study outcomes.
A total of 5521 patients with objectively confirmed ST of the leg who participated in 26 RCTs were included in the current review. It is important to highlight that the methodological quality of the majority of the studies was poor. Additionally, slightly more than 50% of the patients were enrolled in the RCT, which showed that treatment with a prophylactic dose of fondaparinux for 45 days was superior to placebo in reducing the risk of symptomatic thromboembolic complications (1.3% with placebo vs 0.2% with fondaparinux) without an increase in bleeding events. However, this was not associated with a mortality benefit.4 A recent cost analysis of this study showed that fondaparinux was not cost-effective for the treatment of ST of the legs.6
Given that none of the studies in the current review evaluated similar treatments for the same outcomes to ascertain the best treatment option, what should the clinician do for a patient who presents with acute symptomatic ST of the leg? The latest consensus guidelines from the American College of Chest Physicians recommend prophylactic-dose fondaparinux or low-molecular-weight heparin (LMWH) over no anticoagulation, and suggest using fondaparinux over LMWH for extensive ST of the legs.7 Clearly, the type and duration of pharmacological treatment of ST will depend on the patient's presenting signs and symptoms, renal function, risk factors for DVT/PE and cost considerations. For example, in a pregnant or lactating woman the use of LMWH is preferred as it does not cross the placenta and is safe for lactation. For a patient with severe renal insufficiency (creatinine clearance <30 ml/min), unfractionated heparin is the treatment of choice. For all other cases, fondaparinux may be considered specifically in the subgroup of patients at high risk of developing DVT/PE. Shorter durations of treatment need to be further evaluated in future clinical trials.6