You are working in the low acuity zone of the ED when you encounter your first patient. She’s a 75-year-old female with a history of hypertension, diabetes and total right hip replacement 1.5 months ago presenting with left leg swelling and pain. You see the patient and calculate a Well’s score of 3. Your D-Dimer and Ultrasound are ordered and your DOAC prescription is pretty much already written. Then the report comes back – Superficial thrombophlebitis.
Superficial thrombophlebitis or superficial vein thrombosis may not be the first diagnosis you consider when seeing a patient with unilateral leg swelling. This blog post will first explore its pathophysiology, risk factors and clinical implications. Then we will discuss an approach to risk stratification, diagnosis and treatment.
Case resolution at the end of this blog post.
Pathophysiology, Risk factors and Clinical Implication
To begin to understand superficial vein thromboses and thrombophlebites, it’s important to first review the pertinent anatomy. We need to be speaking the same language when we say “superficial” and be familiar with the different types of presentations you may see.
The large majority of superficial vein thromboses occur in the lower extremities so that will be the primary focus of this blog post.
The deep venous system starts with the deep veins of the calf which include the anterior and posterior tibial veins and the fibular veins which combine to form the popliteal vein. The lesser saphenous vein, which is a superficial vein, joins the popliteal vein at approximately the level of the knee. We’ll refer to the area where the lesser saphenous vein joins as the saphenopopliteal junction (SPJ). Proximally, this becomes the femoral vein. Some older sources may refer to the femoral vein as the “superficial femoral vein” which can lead to confusion as this vein is part of the deep venous system.
When the femoral vein is joined by the deep femoral vein and the greater saphenous vein, it becomes the common femoral vein. The area where the greater saphenous vein joins is called the saphenofemoral junction (SFJ). The greater saphenous vein is a superficial vein and the location of 60-80% of superficial thrombophlebites [1]. The other important superficial veins include the lesser saphenous vein and the anterior accessory saphenous veins. These 3 veins can collectively be referred to as the “axial veins”. There are many other superficial and perforating veins that are less clinically relevant to us.
The last category of superficial veins are the tributary or varicose veins.
Nomenclature
The main diagnosis that we’re discussing is superficial vein thrombosis which is a blood clot in a superficial vein. Another term you may see is superficial thrombophlebitis which is essentially synonymous with superficial vein thrombosis as a thrombus in the absence of inflammation would be rare. Both diagnoses may be referred to as the abbreviated “SVT” going forward.
If there is inflammation within a vein but no actual thrombus, the terminology would change to superficial phlebitis.
The last diagnosis, which is outside the scope of this blog post but is important to be familiar with, is septic thrombophlebitis or suppurative thrombophlebitis. This is an infectious process within a vein that may be present with or without associated thrombus.
While DVT is often considered more frequently that SVT, recent large epidemiologic studies have shown that SVT can actually occur up to 6 times more frequently [1].
Risk factors
Who are the patients most likely to present with SVT? Most of the risk factors for SVT are similar to those in DVT.
The basic risk factors include those that affect Virchow’s triad:
Stasis- Endothelial Injury
- Hypercoagulability
General risk factors related to Vichow’s triad include (among others):
- Advanced age
- Elevated BMI
- Immobility
- Recent surgery or hospital admission
- Active malignancy
- Pregnancy, postpartum or exogenous hormone use
Risk factors that are more specific for SVT:
- Any manipulation of a superficial vein including peripheral IV insertion
- Cosmetic treatments of varicose veins such as sclerotherapy [2].
Most important risk factors in SVT = Varicose Veins
What differs in SVT compared to DVT is that the primary risk factor in SVT are varicose veins. 80-90% of cases of SVT occur in the context of this condition. Stasis is the primary mechanism of SVT development in patients with varicose veins while inflammatory/hypercoagulable causes are more common in their absence [3].
Take home point #1:
In the absence of varicose veins, SVT may be a marker for a hypercoagulable state, conditions for which the patient should be evaluated.
This “evaluation” will most likely not be by an ED provider and is usually explored by primary care physicians or thrombosis experts. However, it is important to keep in mind that SVT in the lower extremities in the absence of varicose veins only occurs in 5-10% of patients so we need to keep a high index of suspicion for other risk factors that may not be immediately obvious.
Clinical Significance
Until the last decade or so, many reports incorrectly commented on the benign nature of SVT. Most studies were retrospective in nature, contained a small number of included patients and had largely varying estimates of their relationship with DVT and PE [4].
More recent larger prospective epidemiologic studies showed a clearer association with DVT and PE with 24.9% diagnosed with either DVT or symptomatic PE at the time of diagnosis of SVT. [3] In those with isolated SVT who were followed at 3 months, 8.3% went on to develop a DVT, recurrence or extension of their SVT or symptomatic PE.
The risk factors that were independently associated with increased risk of progression of SVT or progression to DVT/PE included [3]:
- Male sex
- Previous cancer
- Previous DVT/PE
- Absence of varicose veins
A Note on Upper Extremity SVTs:
In upper extremities, most SVTs occur in the context of instrumentation or following IV insertion. Therefore, the main risk factors for upper extremity SVT relate to endothelial trauma that results in venous stasis.
In the quite rare event of seemingly idiopathic upper extremity SVT we would need to keep a high suspicion for other causes. There is a rare, yet clinically relevant, diagnosis to be aware of. This involves a quick history review. Some readers may be familiar with Armand Trousseau, a French Internist from the 1800s who described the well-known “Trousseau sign” in hypocalcemia [5].
What you may be less familiar with is Trousseau’s syndrome. It is a finding of multiple migratory SVT often in the superficial veins of the upper extremities and the chest wall that is caused by a hypercoagulable state associated with underlying malignancy (stomach, pancreas, lung). Ironically and tragically, Dr Trousseau later found this syndrome in himself and then soonafter was diagnosed with and died of gastric cancer.
Risk stratification of superficial thrombophlebites
We can classify SVT into three groups based on their risk for progression to VTE: Low, intermediate and high risk. This classification is based on the treatment recommendations within the Thrombosis Canada guidelines and is only applicable for SVT of the lower extremities. Patients who are found to have a DVT and SVT are not included as they are treated as DVTs typically are.
Low risk
- SVT remote (≥3cm) from the saphenofemoral and saphenopopliteal junctions such as an SVT involving the below-knee rather than above knee greater saphenous vein AND
- Focal SVT with axial vein involvement less than 5 cm in length
- AND
- No medical risk factors for VTE
Intermediate risk
- SVT in proximity (3cm) to the deep venous system, particularly if involving the greater saphenous vein or lesser saphenous vein OR
- SVT that is more extensive with the affected vein segment more than 5cm in length OR
- SVT that propagates with symptomatic care or low risk SVT with risk factors for VTE
- AND
- No medical risk factors for VTE
High risk
- SVT identified initially or that subsequently propagates within 3 cm of the deep venous system, particularly if involving the greater or lesser saphenous veins (SPJ and SFJ) OR
- SVT that propagates despite prophylactic anticoagulation OR
- Recurrent SVT after cessation of anticoagulation
- OR
- SVT in a patient with medical risk factors for VTE
“Medical risk factors” are not clearly defined and require physician judgement. Examples of risk factors include: Prior history of DVT/PE or SVT, cancer, pregnancy, hormonal therapy, recent surgery or trauma
Diagnostic Approach for Superficial thrombophlebites
Historically, SVT was purely a clinical diagnosis however in recent years, the diagnostic approach has become more complex. However, we must still rely on our ability to clinically suspect and evaluate our patients who potentially have the condition.
History:
- In the event of an SVT, patients may report pain, erythema and edema along a superficial vein
- Ask about:
- History of SVT, DVT, and PE
- Classic or atypical VTE risk factors
- Infectious symptoms such as fevers and chills
- Recent instrumentation such as IV insertion or sclerotherapy
- Any patient who is diagnosed with SVT should be screened for current symptoms of PE and investigated appropriately
Physical exam:
- Note the presence or absence of varicose veins and whether patient symptoms are localized to this area
- Some superficial thrombi may be apparent as a thickened palpable cord [6]
- In rare cases of suppurative thrombophlebitis, you may note high fevers, fluctuance and/or purulent drainage from the vein.
- Physical exam may be surprisingly normal even in the event of an underlying SVT. We often think superficial veins are more superficial than they are. In reality, they may be located several centimetres under the skin so the erythema may not actually be visible on the skin. This is even more common in skin of colour or in patients with elevated BMI
D-Dimer + Clinical Risk Scores
D-dimer, which is a fibrin degradation product, is known to be a sensitive yet not specific marker in DVT and PE. In a study that sought to assess the value of D-dimer measurement in the diagnosis of SVT and using the positivity threshold of 500ng/nL (same as in DVT/PE) they found the D-dimer was positive in 68% of cases. They did find that while there was an association between size of SVT and D-Dimer level they could not safely exclude clinically important SVTs such as those extending closely to the saphenofemoral junction with a negative D-Dimer [7].
Other studies showed D-dimer to have a sensitivity of 48-74% for SVT [8-10].
Take home point #2:
D-dimer testing does not reliably rule out SVT. There are no validated clinical risk scores for SVT
Ultrasound
So we know that D-dimer is not very helpful in determining the presence or absence of SVT. Given the general understanding that SVT are more clinically important than previously thought, most experts agree that ultrasound is needed in a majority of cases.
“CUS should be performed in the majority of patients with clinically diagnosed SVT, particularly those with symptoms above the knee or located close to the popliteal fossa, in those with symptoms suggestive of DVT and in patients with VTE risk factors.” – Thrombosis Canada Guidelines
Scenarios where ultrasound can be avoided:
- Isolated upper extremity SVT that is clearly associated with a catheter insertion
- Clinically obvious SVT located in a varicose vein below the level of the knee and without additional clinical risk factors[1].
Unfortunately, once the ultrasound in completed, we may lack the details necessary in order to correctly risk stratify our patients. The treatment that we initiate will be impacted by the size and location of SVT which leads us to our third take-home point:
Take home point #3:
Size and location matter. When you suspect an SVT, clarify the suspected location in your ultrasound requisition. When the length and location of the SVT is not clear, it is important to seek out this information from Radiology
Implement most recent evidence in the treatment of superficial vein thrombosis
Historically, the treatment for SVT was only symptomatic. This could include compressive stockings, topical or oral NSAIDs and warm compresses. While this remains the treatment of choice for low-risk SVT, other therapies are indicated for higher risk cases.
This would also be the treatment of choice for obvious SVT within a varicose vein that is diagnosed clinically. If the patient has higher risk with NSAIDS such as higher bleeding risk, history of peptic ulcer disease, uncontrolled hypertension or AKI, the topical NSAID option would be preferred. In addition to NSAIDS, compression stockings can be recommended for further symptomatic relief. Since the majority of upper extremity SVT are associated with catheter insertion, the first step would be to remove the catheter. Data is limited in the treatment of these SVT but most sources including thrombosis Canada recommend that they be treated with oral or topical NSAIDS only. There is much less evidence on the treatment of SVT compared to DVT. The majority of our data for treating these patients comes from two RCTs. The first is the Calisto trial which is a double blind RCT evaluating the efficacy of fondaparinux for the treatment of SVT [11]. 3002 patients with SVT were randomized to receive fondaparinux or placebo for 45 days. It involved patients from 17 countries and is the basis of the recommendation for the intermediate-risk SVT group. At day 47, the primary outcome, which was the composite of death, symptomatic PE, symptomatic DVT, symptomatic extension to the SFJ or symptomatic extension of the SVT occurred in 0.9% of the fondaparinux group compared to 5.9% in the placebo group with a RRR of 85% in the fondaparinux group. The number needed to treat (NNT) to prevent 1 DVT or PE was 88 and if you included all the elements of the primary outcome, the NNT was 20. There were no differences between safety outcomes (bleeding) between the two groups. An alternative to this is a prophylactic dose of rivaroxaban (10mg PO daily) which was shown to be non-inferior to fondaparinux in the SURPRISE study [12] According to latest evidence, your treatment options for intermediate-risk SVT are: If the patient is symptomatic, you can consider adding compressions stocking and NSAIDS as well. If the patient has a contraindication to fondaparinux or rivaroxaban, an alternative would be an intermediate dose of low molecular weight heparin. Take home point #4 Rule of 3s – If the clot is within 3 cm of the SFJ or SPJ, the patient requires 3 months of full dose anticoagulation (=High risk SVT) As most trials do, pregnant patients were excluded from the RCTs and there is little evidence of their treatment. In most case, it would be reasonable to discuss with thrombosis if unsure of how to treat these patients. Thrombosis Canada’s latest statement for pregnant patients with SVT would be to provide prophylactic doses of LMWH for a period of 1-6 weeks or throughout pregnancy and post-partum period if higher risk features. Those features include bilateral SVT, SVT within 5cm of the deep system or longer than 5cm in length. Let’s Get Practical Note that some of the following may not be applicable to your setting. Some information is specific to Ontario, Canada. We have gone over the evidence for risk stratification, diagnosis and treatment of SVT. Practically speaking, how should we be approaching these patients in the ED? I turned to hematologist and thrombosis expert at The Ottawa Hospital, Dr. Lana Castellucci for answers. She emphasized that due to lack of evidence at this time, there remains much heterogeneity within the thrombosis community. She agreed that our job is first and foremost clinical. We must think of this diagnosis and the differential diagnosis that comes with it and carefully examine our patients. We must also cautiously screen our patients for PE symptoms, hypercoaguable risk factors, and contraindications to anticoagulation. Next step is investigating. In terms of whether or not to order a D-Dimer for the patient, evidence and expert consensus is inconclusive. Dr. Castellucci agreed that the utility of D-Dimer is unclear in the ED and they do not use this marker for trending in SVT like they do in DVT. She also emphasized that the Well’s score is validated for DVT and there are no similar scores for SVT. We must rely on clinical suspicion. If you did decide to workup a patient for DVT and you have a negative D-dimer and low Well’s score but you still have clinical suspicion for SVT, it would be reasonable to obtain ultrasound imaging for patients in this case. This is a reminder that SVT presentations may be subtle and could present with simply atraumatic groin pain. There is also heterogeneity in radiology reporting as most radiology protocols focus mainly on the deep venous system. If an SVT is suspected, it is helpful to mention the location of suspicion in your ultrasound requisition. If an SVT is diagnosed, treatment will depend on clot and patient factors. Ease of medication administration and patient financial means should also factor in our decision, especially considering inability to afford medications is a leading cause of medication non-compliance. Regarding our medication options, there are several things to keep in mind. Fondaparinux can be easily obtained in hospital but are not easily very affordable or convenient as outpatients. Contraindications to fondaparinux are similar to DOACS. This often leaves rivaroxaban as the only “evidence-based drug” option. Fortunately, the patent for this medication recently expired making it quite affordable at $0.71 per tablet (without drug coverage). As EM physicians, we should always consider if a “limited use code” (LU code) is applicable in the clinical setting. This brings us to our final take-home point that could apply for all conditions that we see in the ED. Take home point #5: Consider factors (financial or otherwise) that may impact compliance when you are prescribing a new medication for patients in the ED. For a quick and practical approach, check out the published ‘Just the Facts’ primer in CJEM here. Low risk SVT Treatment:
Intermediate risk SVT Treatment:
High risk SVT Treatment:
SVT in Pregnancy:
Case Conclusion:
References
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