Approach Considerations
The treatment of superficial venous thrombosis depends on the condition’s etiology, extent, and symptoms. Duplex ultrasonography (US) gives an accurate appraisal of the extent of disease and thus allows the administration of a more rational therapy.
For the superficial, localized, mildly tender area of thrombophlebitis that occurs in a varicose vein, treatment with mild analgesics, such as aspirin, and the use of some type of elastic support usually are sufficient. Patients are encouraged to continue their usual daily activities. If extensive varicosities are present or if symptoms persist, phlebectomy of the involved segment may be indicated.
More severe thrombophlebitis, as indicated by the degree of pain, redness, and the extent of the abnormality, should be treated with elevation of the extremity and the application of massive, hot, wet compresses. The latter measure seems to be more effective when a large, bulky dressing, including a blanket and plastic sheeting followed by hot water bottles, is used, taking care to avoid burning the patient.
Anticoagulants are usually not indicated in superficial thrombophlebitis unless the process extends into the deep venous system [25] or persistent inflammation is present in an affected area. [26]
In the case of thrombosis of a hemorrhoid, evacuation of the thrombus, though very painful, usually provides rapid relief. Magnesium sulfate compresses may also be used to alleviate swelling and pain, though surgery is sometimes necessary to remove the clot from the hemorrhoid.
Compression Stockings
Long-leg, heavy-gauge elastic stockings or multiple elastic (Ace) bandages are indicated when the patient becomes ambulatory.
Gradient compression stockings are an often-overlooked adjunctive therapy that is both benign and effective. These highly elastic stockings provide a gradient of compression that is highest at the toes (at least 30-40 mm Hg) and gradually decreases to the level of the thigh. This amount of compression reduces capacitive venous volume by approximately 70% and increases the measured velocity of blood flow in the deep veins by a factor of 5 or more. Gradient compression hose also have been shown to increase local and regional intrinsic fibrinolytic activity.
In the early phases of superficial thrombophlebitis in the leg, dangling the extremity without external support from stockings or elastic bandages leads to leg swelling and increased pain.
Pharmacologic Therapy
Current treatment options are aimed at resolving symptoms, preventing recurrence and most importantly, and preventing extension to the deep venous system, which may potentially result in a thromboembolism. Previous treatment options were based on a Cochrane review published in 2007 that showed that nonsteroidal anti-inflammatory drugs (NSAIDs) and low-molecular-weight heparin (LMWH) are the first options. [27]
A second Cochrane review published in 2013 added, among others, a large randomized control study that included more than 3000 patients with superficial thrombophlebitis and compared fondaparinux with placebo. The investigators found fondaparinux to be a good option for treatment of superficial thrombophlebitis and prevention of some of its associated complications. [28]
A third Cochrane review, published in 2018, found that prophylactic-dose fondaparinux for 45 days appeared to be a valid therapeutic option for most patients. [2] The reviewers noted that further research would be needed to evaluate the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; to determine optimal dosing and treatment duration for varying levels of recurrence risk; and to determine whether combination therapy might be more effective than monotherapy.
Fondaparinux
Fondaparinux is a newer anticoagulant that was derived from the binding region of heparin and antithrombin. It is an inhibitor of factor Xa, and its main uses are the same as those of heparin—more specifically, prevention and treatment of venous thrombosis and pulmonary embolism (PE). Fondaparinux is not shown to interact with platelets and platelet factor 4 and thus theoretically should not cause heparin-induced thrombocytopenia (HIT). Its main advantage over heparin or LMWH is that its bioavailability and half-life (15-17 hours) allow once-daily dosing.
As noted (see above), fondaparinux has been shown to achieve significant reductions in the extension of superficial thrombophlebitis into the deeper venous systems and the rate of recurrence in general, as well as to reduce the symptoms of venous thromboembolism when compared to placebo [28] ; however, there was no difference with respect to the rates of major bleeding. To date, no studies have been done to compare the efficacy of fondaparinux with that of heparin or LMWH in superficial thrombophlebitis.
Use of the lowest dosage of fondaparinux (2.5 mg/day subcutaneously) for 45 days was shown by Decousus et al to suffice for prevention of extension, recurrence, and embolization of superficial venous thrombosis. [29] Another advantage to this anticoagulant medication is that the dosage studied for superficial venous thrombosis does not have to be monitored. At this dosage, fondaparinux has not been shown to affect activated partial thromboplastin time (aPTT), prothrombin time (PT), or bleeding time. [30]
Fondaparinux should be avoided in patients with kidney function compromise, active bleeding, bacterial endocarditis, and body weight below 50 kg. One downside to the use of fondaparinux is that there is currently no antidote, especially for the low dosage used for superficial thrombophlebitis treatment. Also, because this agent is cleared by the renal system, prolonged administration warrants renal function monitoring and should be discontinued if creatinine clearance is less than 30 mL/min.
Low-molecular-weight heparin
The 2007 Cochrane review cited above suggested that anticoagulation with LMWH is better in reducing local signs and symptoms, along with reducing propagation to deep venous thrombosis (DVT). [27] In addition, LMWH is useful in preventing the progression of thrombosis and is recommended when there is evidence of DVT.
Patients with contraindications to anticoagulation or those receiving adequate anticoagulation treatment who have progression of thrombosis should be considered for saphenous ligation at the junction with the deep venous system.
Nonsteroidal anti-inflammatory drugs
The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) is similar to that of LMWH in reducing the risk of extension of superficial thrombophlebitis into the deep venous system along with decreasing recurrence. In addition, NSAIDs are often more practical and more easily administered than LMWH. No NSAID has not been shown to be superior to others in the treatment of superficial thrombophlebitis.
Antibiotics
Antibiotics are not routinely indicated for treatment of superficial thrombophlebitis, in that the erythema and tenderness are local inflammatory reactions, not allergic reactions. However, if suppurative thrombophlebitis may be present, then antibiotics should cover skin flora and anaerobic organisms, especially if an abscess is present. One should also consider coverage with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) if the local population warrants this.
Local thrombolytics
No adequate studies have been performed on the use of local thrombolytics, and they were excluded from the Cochrane Database of Systematic Reviews article. Therefore, at this time, their use is not recommended.
Related studies
Patients who present with thrombosis of the great saphenous vein (GSV) or the small saphenous vein (SSV) should be considered for anticoagulation or ligation of the vein, given that a high incidence (6-44%) of concurrence or progression to DVT has been reported in such patients. In a study, Ascher et al reported that 65.6% of patients who presented with GSV thrombosis were found to have associated DVT. [31]
A meta-analysis of the prevalence of DVT and PE in patients with superficial vein thrombosis found a weighted mean prevalence of 18.1% for DVT and 6.9% for PE in patient with superficial thrombophlebitis. The authors concluded that in selected patients with superficial thrombophlebitis, screening for DVT or PE may be warranted. [32]
Optimal treatment of saphenous vein thrombosis remains controversial. As noted by Wichers et al in a systematic review, a lack of randomized trials has prevented evidence-based recommendations in this area. [18]
In a small, randomized trial of 60 patients with GSV thrombosis, Lozano et al compared treatment using LMWH with surgical saphenous ligation. [33] Patients in the LMWH group experienced no episodes of DVT or PE but had a 10% incidence of recurrent superficial venous thrombosis. Among the patients treated surgically, two pulmonary emboli (6.7%) were found, and one episode of recurrent superficial venous thrombosis (3.3%) occurred.
In a larger randomized trial (Stenox study), no statistical difference in the incidence of DVT or PE was found between patients with superficial venous thrombosis who were treated with placebo, with NSAIDs, or with two doses of LMWH. In the study, 436 patients were randomized to one of the three groups; all patients wore compression stockings.
The study’s placebo group had a higher incidence of recurrent superficial venous thrombosis than did the other patients. Interestingly, the results in the group treated with NSAIDs were the same as those in the patients treated with LMWH.
Similar to the outcome of the above study, Wichers et al concluded, after a systematic review of the literature, that LMWH or NSAID therapy appears to reduce the incidence of superficial venous thrombosis extension or recurrence. [18] Larger trials are likely required to demonstrate differences in the incidence of DVT.
Treating patients with some form of low- or intermediate-dose anticoagulation appears reasonable at this time; this should be followed by repeat duplex US to look for progression at regular intervals for a few weeks to a month. In patients with stable nonprogressing thrombus, anticoagulation therapy can probably be discontinued in the absence of other risk factors.
SURPRISE trial
The SURPRISE trial was a randomized, open-label, blinded outcome event adjudication trial that compared rivaroxaban 10 mg once daily with fondaparinux 2.5 mg once daily in 472 patients with superficial vein thrombosis who were at risk for venous thromboembolism (VTE) and complications. [34] Both groups were treated for 45 + 5 days and had an observational period of 90 + 10 days.
The investigators looked at primary efficacy outcome as a composite endpoint of deep venous thrombosis (DVT), pulmonary embolism (PE), progression of superficial vein thrombosis towards the saphenofemoral junction, recurrence of superficial venous thrombosis and all-cause mortality at day 45. [34] The trial was designed to show noninferiority of rivaroraxaban compared to fondaparinux in terms of primary endpoints and risk of major bleeding.
The investigators found that the primary efficacy outcome occurred in 3.3% of patients receiving rivaroxaban and 1.8% of patients receiving fondaparinux. [34] On the basis of this finding, the absolute difference between rivaroxaban and fondaparinux was 1.53% (P = .025 for noninferiority). Rivaroxaban 10 mg once daily was shown to be noninferior to fondaparinux 2.5 mg once daily for treatment of superficial venous thrombosis. The incidence of clinically significant nonmajor bleeding was 2.5% at 45 days and 2.5% at 90 days for rivaroxaban versus 0.4% at 45 days and 0.9% at 90 days for fondaparinux.
Noninferiority was shown for rivaroxaban with no statisically significantly increased rate of major bleeding as compared with fondaparinux. [34] No data were collected on comparative quality of life between the two medication regimens. This is an important consideration, in that rivaroxaban is given orally once daily and fondaparinux as a subcutaneous injection once daily. The authors state that this consideration will have to be addressed in further studies.
Excision and Ligation
With persistence or spread of the process, the thrombophlebitic vein may be excised. [35] Patients who demonstrate signs and symptoms of septic thrombophlebitis require urgent venous excision to control the septic focus. This is usually performed through a direct incision over the vein, allowing removal of the infected thrombosed segment along with wide debridement of any surrounding infected or necrotic tissue. Cultures are sent to guide antibiotic therapy.
Surgical treatment may also be considered for patients with saphenous thrombophlebitis. This is most often considered if the process extends upward toward the femoral or popliteal vein despite anticoagulation or in a patient with a contraindication to systemic anticoagulation.
Whether surgical ligation or anticoagulation is the best initial treatment for saphenous vein thrombosis without deep venous involvement remains controversial. If saphenous ligation is chosen, high ligation at the saphenofemoral or saphenopopliteal junction is recommended, with ligation of any branches near the junction. For saphenopopliteal procedures, US mapping for guidance is recommended because of the variability in location of the saphenopopliteal anatomy.
Puncture and Evacuation
A painful section of a superficial vein containing a palpable intravascular coagulum may be treated by puncture incision with an 18-gauge needle and evacuation of the clot after local anesthesia. This procedure often produces marked rapid relief and rapid resolution of the inflammation.
Puncture and evacuation is less effective in the first week after the onset of symptoms, because the vessel wall is thickened and the coagulum itself is more cohesive during the early phase of phlebitis.
Treatment of Septic and Suppurative Thrombophlebitis
If thrombophlebitis is associated with a cannula or a catheter, the device should be immediately removed and cultured. If the patient is in a septic state, appropriate antibiotics should be given. If suppurative thrombophlebitis is suspected, immediate and complete excision of all of the involved veins is indicated. The wound may be left packed open for secondary closure or skin grafting at a later date. The use of appropriate systemic antibiotics is always indicated.
If the suppurative process involves one of the deep veins, aggressive antimicrobial and anticoagulant therapy are necessary.
If a venous segment involved in superficial thrombophlebitis is suspected to be a source of bacteremia but does not require excision, it can be aspirated in order to culture the contents of the venous lumen. This may be helpful in immunocompromised patients with phlebothrombosis and positive blood cultures.
Long-Term Monitoring
Follow-up should be performed 2-3 days after treatment for superficial thrombophlebitis, either with an office visit or by telephone, to be sure that the patient is progressing in a satisfactory manner.
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Deep venous thrombosis.
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Thrombosis of great saphenous vein and tributaries. Note lack of full compressibility of vein secondary to intraluminal thrombus. Courtesy of Wikimedia Commons ©Nevit Dilmen.
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Blood coagulation (thrombin) and protein C pathways. Courtesy of Wikimedia Commons ©John H Griffin, PhD.