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Clinical Knowledge Summaries: Previous version Thrombophlebitis

Thrombophlebitis
This PRODIGY guidance topic is obsolete and has been replaced by a CKS Topic Review.
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About this topic


Have I got the right topic?
Age from 16 years onwards
This guidance covers the management of superficial thrombophlebitis.
This guidance does not cover the management of deep vein thrombosis.
There is a separate CKS topic on Deep vein thrombosis.
The target audience for this guidance is healthcare professionals working within the NHS in
England, and providing first contact or primary health care. The Shared decision making sections
are designed to provide a focus for discussion during the consultation about the treatment
options.

Changes
Version 1.0.0, revision planned in 2009.
Last revised in February 2006
JulySeptember 2005 reviewed. Validated in December 2005 and issued in February 2006.

Previous changes
July 2005 updated to include prescribing information for compression stockings. Issued in
July 2005.
April 2002 reviewed. Validated in June 2002 and issued in July 2002.
February 1999 written. Validated in April 1999 and issued in May 1999.

Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 March 2007.
HTAs (Health Technology Assessments)
No new HTAs since 1 March 2007.
Economic appraisals
No new economic appraisals relevant to England since 1 March 2007.
Systematic reviews and meta-analyses
A new Cochrane review has been published since the last revision of this CKS topic.
Di Nisio, M., Middeldorp, S. and Wichers, I.M. (2007) Treatment for superficial thrombophlebitis
of the leg (Cochrane Review). The Cochrane Library. Issue 1. Chichester, UK: John Wiley & Sons,
Ltd. www.thecochranelibrary.com [Accessed: 19/03/2007]. [Free Full-text]
Primary evidence
No new high quality randomized controlled trials since 1 March 2007.

New policies
No new national policies or guidelines since 1 March 2007.

New safety alerts


No new safety alerts since 1 March 2007.

Changes in product availability


No changes in product availability since 1 March 2007.

Concise knowledge for clinical scenarios


Which therapy?
There is no good evidence to guide choice of treatments, and the following recommendations are
based on expert opinion:

Treat pain with an oral nonsteroidal anti-inflammatory drug (NSAID), as their antiinflammatory effect is thought to be helpful.
If intolerant of NSAIDs, paracetamol is a suitable alternative painkiller.

This PRODIGY guidance topic is obsolete and has been replaced by a CKS Topic Review.
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Clinical Knowledge Summaries: Previous version Thrombophlebitis

Although there is no evidence for its use, some people may find local heat helpful (e.g. by
the application of a warm moist towel or flannel to the affected limb).
Consider prescribing a compression stocking if a leg vein is affected, as these are
thought to help reduce pain, improve venous blood flow, and reduce the chance of
thrombosis extending or recurring.
Advise leg elevation when resting if a leg vein is affected, as leg elevation is thought
to improve venous blood flow and reduce swelling.
Encourage people to keep mobile bed rest is not advised.
Anticoagulants are not usually indicated for superficial thrombophlebitis if deep vein
thrombosis is suspected, arrange for urgent referral.
Antibiotics are not indicated in aseptic superficial thrombophlebitis (which accounts
for most cases of superficial thrombophlebitis).
Consider the possibility of septic superficial thrombophlebitis if there is a break in
the skin (e.g. with intravenous cannulation or drug abuse) although it can occasionally
occur spontaneously.
o
Admission is generally required for antibiotic treatment.
o
Intravenous drug abusers may have unusual infections, including botulism, MRSA
(methicillin-resistant Staphylococcus aureus) and Streptococcus Group A, and
treatment of these people requires admission or specialist advice.
o
Mild superficial thrombophlebitis can be treated in primary care with flucloxacillin, or a
macrolide (erythromycin or clarithromycin). Note: antibiotics may not be necessary for
very mild cases.

Practical prescribing points


For further information please see the Medicines Compendium (www.medicines.org.uk) or the
British National Formulary (www.bnf.org).

Nonsteroidal anti-inflammatory drugs

Only one nonsteroidal anti-inflammatory drug (NSAID) should be prescribed at a


time.
NSAIDs may worsen asthma, hypertension, renal impairment, or heart failure.
People with cardiovascular disease: ibuprofen may reduce the cardiovascular protective
effect of low-dose aspirin.
In people with risk factors for gastrointestinal NSAID complications (e.g. past
history of peptic ulcer):
o
Use paracetamol instead of an NSAID if possible, or
o
Use gastroprotection (a proton-pump inhibitor or full-dose misoprostol) combined with
a standard NSAID.
Risk factors for gastrointestinal NSAID complications include:
o
Age 65 years and over.
o
Previous history of gastroduodenal ulcer, bleeding, or perforation.
o
Concomitant use of drugs that are known to increase the likelihood of upper
gastrointestinal adverse events (e.g. anticoagulants, aspirin, and corticosteroids).
o
Presence of serious comorbidity, such as cardiovascular disease, renal or hepatic
impairment, or diabetes.
o
Requirement for prolonged duration of NSAID use.
o
Use of maximum recommended doses of NSAIDs.
Pregnancy and breastfeeding: use paracetamol if possible. If an NSAID is essential,
ibuprofen may be used during breastfeeding and before 30 weeks of pregnancy. NSAIDs
should not be used after 30 weeks of pregnancy as they are associated with an increased
risk of premature closure of the ductus arteriosus and oligohydramnios.

Compression stockings

If compression hosiery is prescribed, it is essential to check that arterial


circulation is not compromised. Such assessment would usually include measurement of
the ankle-brachial pressure index (ABPI) by Doppler (see the CKS topic on Leg ulcer
venous).
o
ABPI less than 0.5: arterial disease is likely and compression treatment is
contraindicated.
o
ABPI between 0.5 and 0.8: assume that the person has arterial disease.
Compression in such instances may further compromise arterial blood supply and
should be generally avoided.
o
ABPI greater than 0.8: graduated support stockings may be applied safely.
Arterial disease may develop in people with venous disease, and health professionals
should be aware that the ABPI may drop after the initial measurement [Royal College of
Nursing, 2000].

This PRODIGY guidance topic is obsolete and has been replaced by a CKS Topic Review.
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Clinical Knowledge Summaries: Previous version Thrombophlebitis

Antibiotics

Erythromycin commonly causes gastrointestinal adverse effects. If gastrointestinal


adverse effects are known to occur, consider prescribing clarithromycin instead.
Erythromycin and clarithromycin may increase the level of certain drugs (e.g.
theophylline, carbamazepine) or potentiate the effects of warfarin, and increased monitoring
of these drugs may be necessary. There is an increased risk of myopathy when
erythromycin or clarithromycin are given with statins.

Should I refer or investigate?


Refer?

Always admit:
o
If there is suppurative thrombophlebitis
o
If there is clinical evidence of a deep vein thrombosis (DVT)
o
If chest pain or dyspnoea are present, as either may indicate pulmonary embolism
Admit or arrange urgent hospital assessment if DVT is suspected. Particularly
suspect DVT if:
o
Thrombophlebitis is mid-thigh extending towards the sapheno-femoral junction. Duplex
scanning is advisable to determine the extent of thrombus propagation.
o
If other risk factors are present, such as past history of DVT, bilateral involvement,
recent bed rest or immobilization, or involvement of a non-varicose vein (see What are
the risk factors?).
Admit people with septic thrombophlebitis unless mild.
o
Particularly consider the possibility of septic thrombophlebitis if there is a break in the
skin (e.g. with intravenous cannulation or drug abuse).
o
There is no guidance in the literature regarding criteria for admission. People who are
systemically unwell or with enlarged lymph nodes or tracking should always be
admitted but it should be remembered that even people with mild symptoms can
deteriorate rapidly.
o
Use clinical judgement, with special caution in high risk groups such as drug addicts
who may have unusual infections, including botulism, MRSA (methicillin-resistant
Staphylococcus aureus) and Streptococcus Group A.
Consider referral for varicose vein surgery if symptoms persist or if extensive
varicosities are present.

Investigate?

Suspect underlying disease if thrombophlebitis occurs in a previously normal superficial vein


and there is no obvious predisposing cause. Consider a thrombophilia screen (seek advice
from a haematologist on which tests to carry out).
Migratory or recurrent thrombophlebitis is an indication for a more detailed evaluation in
search of malignant lesion, or Behet's syndrome or Buerger's disease.

Follow-up advice

Generally no follow-up is needed if symptoms and signs resolve.


Warn that superficial thrombophlebitis can progress into the deep veins and that any
increase in pain or calf swelling warrants immediate medical review. Any symptoms that
suggest the possibility of pulmonary embolism should also be reported immediately.

Prescriptions
Ibuprofen tablets: 400mg three times a day
Age from 16 years onwards

Ibuprofen 400mg tablets. Take one tablet three times a day. Supply 42 tablets.
NHS Cost 1.65
OTC Cost 2.91
Licensed use: yes

Ibuprofen tablets: 400mg four times a day


Age from 16 years onwards

Ibuprofen 400mg tablets. Take one tablet four times a day. Supply 56 tablets.
NHS Cost 2.21
OTC Cost 3.89
Licensed use: yes

Diclofenac sodium e/c tablets: 25mg three times a day


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Age from 16 years onwards

Diclofenac sodium 25mg gastro-resistant tablets. Take one tablet three times a day. Supply
42 tablets.
NHS Cost 1.16
Licensed use: yes

Diclofenac sodium e/c tablets: 50mg twice a day


Age from 16 years onwards

Diclofenac sodium 50mg gastro-resistant tablets. Take one tablet twice a day. Supply 28
tablets.
NHS Cost 0.96
Licensed use: yes

Diclofenac sodium e/c tablets: 50mg three times a day


Age from 16 years onwards

Diclofenac sodium 50mg gastro-resistant tablets. Take one tablet three times a day. Supply
42 tablets.
NHS Cost 1.44
Licensed use: yes

Naproxen tablets: 250mg twice a day


Age from 16 years onwards

Naproxen 250mg tablets. Take one tablet twice a day. Supply 28 tablets.
NHS Cost 1.96
Licensed use: yes

Naproxen tablets: 500mg twice a day


Age from 16 years onwards

Naproxen 500mg tablets. Take one tablet twice a day. Supply 28 tablets.
NHS Cost 2.19
Licensed use: yes

Paracetamol tablets: 1g up to four times a day


Age from 16 years onwards

Paracetamol 500mg tablets. Take two tablets every 4 to 6 hours when required for pain
relief. Maximum of 8 tablets in 24 hours. Supply 100 tablets.
NHS Cost 1.82
OTC Cost 3.21
Licensed use: yes
Patient Information: You may find that your paracetamol works best if you take it regularly
four times a day to start with.

Class I below-knee stocking


Age from 16 years onwards

Compression hosiery class I below knee stocking circular knit standard stock size. One pair
of circular knit, below-knee class I compression stockings to be measured and fitted in the
pharmacy. Supply 2 single stockings.
NHS Cost 6.41
OTC Cost 15.06
Licensed use: yes
Patient Information: You can chose to have the following types of stockings: stockings with
a closed heel and toe, stockings with an open toe. Put the stocking(s) on first thing in the
morning and remove before you go to bed.

Multi-therapy: Thigh-length stockings (class I) with suspender belt

Class I thigh-length stockings


Age from 16 years onwards

Compression hosiery class I thigh length stocking circular knit standard stock size. One pair
of circular knit, thigh length class I compression stockings to be measured and fitted in the
pharmacy. Supply 2 single stockings.
NHS Cost 7.02
OTC Cost 16.50

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Licensed use: yes


Patient Information: You can choose to have any of the following types of stockings:
stockings with a closed heel and toe, stockings with an open toe. Put the stocking(s) on first
thing in the morning and remove before you go to bed.

Suspender belt
Age from 16 years onwards

Suspender belt. Use as directed. Supply 2 belts.


NHS Cost 9.36
Licensed use: no

Flucloxacillin capsules: 500mg four times a day


Age from 16 years onwards

Flucloxacillin 500mg capsules. Take one capsule four times a day for 7 days. Supply 28
capsules.
NHS Cost 6.52
Licensed use: yes

Erythromycin e/c tablets: 500mg four times a day


Age from 16 years onwards

Erythromycin 250mg gastro-resistant tablets. Take two tablets four times a day for 7 days.
Supply 56 tablets.
NHS Cost 6.44
Licensed use: yes

Clarithromycin tablets: 500mg twice a day


Age from 16 years onwards

Clarithromycin 500mg tablets. Take one tablet twice a day for 7 days. Supply 14 tablets.
NHS Cost 21.44
Licensed use: yes

Drug rationale
Drugs not included

Anticoagulants are not usually indicated for superficial thrombophlebitis. If deep vein
thrombosis is suspected, arrange for urgent referral.
Antiplatelets: because superficial thrombophlebitis is primarily due to inflammation and
fibrin clot there is no evidence of value for antiplatelet drugs [Feied and Handler, 2004b].
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended
because there are no good quality trials that compare the efficacy of topical NSAIDs with the
same NSAID given orally or with paracetamol [Moore et al, 1998; Heyneman et al, 2000;
Gotzsche, 2005].
NSAIDs (other than ibuprofen, diclofenac, and naproxen) that are associated with a
higher risk of gastrointestinal adverse events or that are not licensed for general
musculoskeletal pain and inflammation are not recommended [CSM, 1994; Henry et al,
1996; Hernndez-Diaz and Rodriguez, 2000].
NSAID modified-release preparations: improvement in efficacy and reduction in adverse
events have not been shown [Eccles et al, 1998]. Modified-release formulations are also
relatively expensive.
Cyclo-oxygenase 2 (COX-2) selective inhibitors are not recommended. Standard
NSAIDs have a good balance of efficacy versus adverse effects. The evidence suggests that
selective COX-2 inhibitors, as a class, may cause an increased risk of thrombotic events
(e.g. myocardial infarction and stroke) compared with placebo and some NSAIDs, and the
risk may increase with dose and duration of exposure [CSM, 2005].
Topical heparinoid preparations: there are no good quality controlled trials of topical
heparinoid preparations. The trials that there have been were poorly designed and the
patient numbers were generally small.

Drugs included

Standard NSAIDs: ibuprofen, diclofenac, and naproxen have a good balance of


efficacy versus adverse effects. Ibuprofen is associated with the lowest risk of
gastrointestinal adverse effects and should be tried first before diclofenac and naproxen,
which are associated with intermediate risk [CSM, 1994; Garcia and Jick, 1994; Bandolier,
1996; Henry et al, 1996; Hernndez-Diaz and Rodriguez, 2000].
Paracetamol is an alternative analgesic for people who cannot take an NSAID.

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Compression stockings may be considered, however there is no evidence to support their


use and there is conflicting advice in the literature. Follow local guidelines where they exist
and use clinical judgement. Compression hosiery is not appropriate where there is evidence
of significant arterial disease.
Flucloxacillin, or a macrolide such as erythromycin or clarithromycin are recommended
for the treatment of mild septic thrombophlebitis in people who are not in a high risk group
e.g. intravenous drug abusers.

Shared decision making

Thrombophlebitis usually goes within 26 weeks.


Keep on with normal activities as much as possible.
A hot flannel placed over the vein may ease the pain.
Keep an affected leg raised when you rest.
Support stockings may ease discomfort, particularly if you have varicose veins.
Anti-inflammatory painkillers, such as ibuprofen, will often ease the pain.
Paracetamol is an alternative.
Occasionally the vein becomes infected, or a blood clot may extend to a deep vein, or a rare
condition causes the inflammation. Tell a doctor if:
o
Symptoms become worse
o
Inflammation spreads up the inner part of your thigh towards your groin
o
Your whole leg swells
o
Large parts of your leg become warm
o
You develop any new breathing problems, or get chest pains
o
You have recurring bouts of thrombophlebitis

Detailed knowledge about this topic


Goals and outcome measures
Goals

To alleviate symptoms
To identify and manage complications (e.g. deep vein thrombosis)

Background information
What is it?

Superficial thrombophlebitis (superficial vein thrombosis or 'phlebitis') is inflammation


and associated thrombus formation in superficial veins, usually the long saphenous vein of
the leg and its tributaries.
Superficial thrombophlebitis is most often associated with one of the components of
Virchow's triad [Johnson, 2004]:
o
Damage to the blood vessel wall (as a result of trauma, infection, or inflammation)
o
Stasis of blood flow
o
Hypercoagulability of blood
Thrombophlebitis frequently occurs in varicose veins, probably because of local
trauma or stasis [Messmore et al, 1991].
Thrombophlebitis in normal superficial veins may be due to [Messmore et al, 1991]:
o
Internal trauma (e.g. from phlebotomy, intravenous fluids)
o
Infection from an indwelling catheter
o
Chemical irritation from intravenous medications (e.g. diazepam, contrast media)
Infected thrombophlebitis is usually a complication of either a skin infection, intravenous
cannulation, or intravenous drug abuse, although it can occasionally occur spontaneously.
Rarely, it may be secondary to a primary infectious disease (mainly syphilis and psittacosis)
[Samlaska and James, 1990b; Scheld and Sande, 2005]. It is more likely to occur in people
with diabetes, liver disease, malabsorption, or malignancy, or in people who are taking
immunosuppressive drugs [Feied and Handler, 2004b].
o
Septic thrombophlebitis describes infection of a superficial vein without frank
purulence. It must be assumed to be present when a person has cellulitis, abscess, a
break in the skin, or fever [Feied and Handler, 2004b].
o
Suppurative thrombophlebitis describes frank purulence, where pus can be expressed
from a vein. It is usually associated with generalized septicaemia [Feied and Handler,
2004b].

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Migratory thrombophlebitis (thrombophlebitis migrans) is defined as thrombophlebitis in


a small segment of vein that resolves in one area and begins in another [Belcaro et al,
1999].

How common is it?

Superficial thrombophlebitis is thought to be a relatively common condition, but


there are few data on how frequently it occurs.
The lifetime incidence in people with untreated varicose veins has been estimated at 25
50% [Feied and Handler, 2004a].
The long saphenous vein is involved in 6080% of cases and the short saphenous vein in
1020% of cases. Thrombophlebitis is more common in venous tributaries rather than the
saphenous trunk [Leon et al, 2005].
Bilateral involvement has been reported in 510% of affected individuals [Leon et al,
2005].
Pregnancy: there is an increased incidence of superficial thrombophlebitis, particularly in
the puerperium. Increased age, parity, and hypertension are predisposing factors [Samlaska
and James, 1990b]. A retrospective study of 30,040 pregnant women found an incidence of
1 in 200, with most occurring in the first 48 hours post-partum [James et al, 1996].

What are the risk factors?

The most important risk factors for developing superficial thrombophlebitis are a past
history of:
o
Superficial thrombophlebitis
o
Deep vein thrombosis
o
Pulmonary embolism
Other risk factors include a history of either primary or secondary hypercoagulable states.

Hypercoaguable states

The risk of developing superficial thrombophlebitis is increased in conditions known to


increase thrombotic tendency [Samlaska and James, 1990a; Samlaska and James, 1990b].
These hypercoaguable states are classified as:
o
Primary: there is a specific measurable defect in the proteins of coagulation or the
fibrinolytic system. Many of these conditions are hereditary.
o
Secondary: clinical conditions associated with an increased risk of thrombosis. These
include conditions that increase the hypercoagulability of blood (e.g. malignancy,
pregnancy, use of oral contraceptives), and conditions that affect the other components
of Virchow's triad (i.e. damage to the blood vessel wall or venous stasis).

Primary hypercoagulable states

Examples of primary hypercoagulable states are [Samlaska and James, 1990a; Feied
and Handler, 2004a]:
o
Antithrombin and heparin cofactor II deficiencies
o
Protein C and Protein S deficiencies
o
Factor V Leiden
o
Disorders of the fibrinolytic system
o
Dysfibrinogenemias
o
Lupus anticoagulant and anticardiolipin antibody syndrome
o
Prothrombin gene variant

Secondary hypercoagulable states

Abnormalities of coagulation and fibrinolysis:


o
Malignancy: many cancers are associated with an increased risk of superficial and
deep vein thrombosis. People with cancer of the pancreas, stomach, lung, prostate,
colon, ovaries, or gallbladder are particularly likely to develop thrombosis. The
incidence may be as high as 50% in people with pancreatic cancer [Samlaska and
James, 1990b].
o
Pregnancy: there is an increase in all procoagulant factors except factor XIII, and
there is also evidence of reduced fibrinolytic activity. There is a large increase in the
incidence of phlebitis in the puerperium.
o
Oral contraceptives.
o
Infusion of prothrombin factor concentrates that are used to treat congenital disorders
of coagulation.
Conditions that promote venous stasis:
o
Varicose veins
o
Immobilization

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o
Recent surgery
o
Obesity
o
Long haul flight
o
Advanced age
Intravenous therapy and drug abuse:
o
Intravenous catheters
o
Intravenous solutions
o
Sclerotherapy
o
Intravenous drug misuse:

Drug addicts are susceptible to superficial thrombophlebitis because of repetitive


trauma, unsterilized techniques, and irritation caused by the drug mixtures.

Street drugs are often cut with substances that promote thrombosis (e.g. lactose,
sucrose, dextrose). Cocaine in particular seems to promote thrombosis [Samlaska
and James, 1990b].
Endothelial dysfunction. There are three diseases that are due to endothelial dysfunction
caused by primary immunologic mechanisms or direct tissue injury [Samlaska and James,
1990b; Lehner, 2003; Burns, 2004; Johnson, 2004]:
o
Behet's syndrome is a rare condition in which there is a classical triad of oral
ulceration. genital ulceration, and uveitis. Vascular complications include superficial
migratory thrombophlebitis, deep vein thrombosis, and superior and inferior vena cava
thrombosis [Lehner, 2003].
o
Buerger's disease (thromboangiitis obliterans) is a rare condition in which gangrene
occurs due to inflammation and thrombosis of the arteries and veins in the hands and
feet. It most commonly occurs in young men who smoke cigarettes. Small studies have
described superficial migratory thrombophlebitis in 2766% of people with Buerger's
disease.
o
Mondor disease is a rare condition characterized by thrombophlebitis of the
subcutaneous veins of the anterior chest wall, in particular the lateral thoracic vein, the
thoracoepigastric vein, and the superior epigastric vein. Two thirds of affected people
are women. It is usually a benign condition that spontaneously resolves over 2
4 weeks, but it has been associated with breast cancer.
Infectious disease:
o
Septic thrombophlebitis
o
Psittacosis
o
Secondary syphilis

[Samlaska and James, 1990b; DePalma and Johnson, 2000; Schonauer et al, 2003; Feied and
Handler, 2004a; Leon et al, 2005]

How do I know my patient has it?


History

There may be a history of:


o
Gradual onset of localized tenderness followed by redness along the course of a
superficial vein
o
Local trauma (e.g. intravenous infusion or catheter, injection, or phlebotomy)
o
Previous episodes of superficial thrombophlebitis, deep vein thrombosis, or venous
thromboembolism
o
Recent immobility
o
Recent surgery
o
Varicose veins
o
Current or recent pregnancy
o
Oral contraceptive use
o
Malignancy
o
Intravenous drug misuse
o
Thrombophilia
o
Diseases associated with endothelial dysfunction
Enquire into family history, and the age when the first episode occurred.

[Feied and Handler, 2004a; Feied and Handler, 2004b; Johnson, 2004]

Examination

Pain, tenderness, warmth, and redness along the course of a vein are diagnostic
features [Messmore et al, 1991].
The thrombosed veins feel like cords (knots) or a chain of nodules [Messmore et al, 1991].

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Fever, lymphangitis, and signs of systemic upset (especially if septic thrombophlebitis) may
also be present.
Redness and oedema may extend for some distance into surrounding tissue making
distinction from infection difficult [Mortimer and Burnand, 2004].
Thrombophlebitis in a varicose vein may extend up and down the saphenous vein or it may
remain localized in a cluster of tributary varicosities [Johnson, 2004].
Always examine for a deep vein thrombosis. Clinical features may be absent or include
one or more of the following:
o
Swelling of the calf or thigh in one leg
o
Pain and tenderness along the line of the deep venous system
o
Low-grade pyrexia (uncommon)
o
Increased skin temperature
o
Distension of superficial veins
o
Colour change (red or purple)
In septic superficial thrombophlebitis the initial site of infection may be a well-localized
area of tenderness and redness. There may be lymphangitis, lymphadenopathy, localized
cellulitis, inflammation along the course of a vein, and systemic upset (e.g. fever).
Intravenous drug misusers often have a localized area of cellulitis or frank abscesses at the
site of the injection [Samlaska and James, 1990b; Feied and Handler, 2004b]. In
suppurative superficial thrombophlebitis, pus can be expressed from a vein and there is
often septicaemia [Feied and Handler, 2004b].

Investigations

The diagnosis of thrombophlebitis is usually made through history and examination alone
[Messmore et al, 1991].
If superficial thrombophlebitis occurs in a vein that is not varicose and there is no obvious
predisposing cause, suspect an underlying condition that predisposes to thrombophlebitis,
particularly if episodes are recurrent or occur at an early age [Mottahedeh and Da Silva,
2003; Leon et al, 2005].
o
Consider a primary hypercoagulable state, particularly if there is a family history of
thrombosis or if the affected vein is non varicose. Consider seeking advice from a
haematologist on appropriate tests to carry out and their interpretation.
o
If a secondary hypercoagulable state is suspected (e.g. possible cancer) arrange
appropriate investigations.

What else might it be?

Cellulitis
Deep vein thrombosis (DVT)
Tendonitis
Soft tissue trauma
Cutaneous polyarteritis nodosa
Sarcoidal granuloma
Erythema nodosum
Lymphangitis
Neuritis
Ruptured medial head of gastrocnemius

[Samlaska and James, 1990b; Wasserman et al, 1997; Belcaro et al, 1999; Johnson, 2004]

Complications and prognosis


Complications
Aseptic superficial thrombophlebitis
Although superficial thrombophlebitis is usually a benign self-limiting disease, it has been
associated with extension into the deep venous system and pulmonary embolism. The incidence
of deep vein thrombosis and pulmonary embolism in people with superficial thrombophlebitis in
UK general practice is not known but is likely to be much lower that the figures quoted in the
following studies, which were carried out in people who had already been referred to a specialist.
Deep vein thrombosis

Superficial thrombophlebitis can extend through perforating veins to involve the adjacent
deep veins. In people with hypercoaguable states, deep vein thrombosis (DVT) may also be
present at other sites in the same or opposite leg [Feied and Handler, 2004a].
Studies in people with superficial thrombophlebitis have found a frequency of deep vein
involvement (detected by duplex ultrasound scanning) ranging from 657%. Many of these
studies were in people who had been referred to vascular laboratories [Bergqvist and

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Jaroszewski, 1986; Jorgensen et al, 1993; Bendick et al, 1995; Chengelis et al, 1996;
Blumenberg et al, 1998].
These figures seem alarming but it should be remembered that the incidence in UK general
practice is likely to be much lower.

Pulmonary embolism

Pulmonary embolism (PE) has been reported in people with superficial thrombophlebitis.
Usually the embolus has resulted from a co-existing deep vein thrombosis (DVT), but there
is some evidence that thrombus from the superficial veins can embolize to the lungs with no
obvious deep vein involvement.
The incidence of PE in people with superficial thrombophlebitis presenting in UK general
practice is unknown.
The frequency of PE has been reported as 033%.
o
One study reported a clinical incidence of less than 1% in 232 people referred to a
vascular laboratory [Blumenberg et al, 1998].
o
Higher figures have been reported from studies that have diagnosed PE by lung
perfusion scanning (e.g. 4% in a study of 186 people with superficial thrombophlebitis
who had been referred for duplex scanning) [Lutter et al, 1991].
o
One small study (21 people) with superficial thrombophlebitis of the proximal greater
saphenous vein found that 7 people (33%) had evidence of a PE detected by perfusion
lung scanning, although only one person had clinical symptoms of a PE [Verlato et al,
1999].

Minor complications

Hyperpigmentation over the affected vein may occur [Johnson, 2004].


A persistent firm nodule may develop in subcutaneous tissue at the site of the affected vein
[Johnson, 2004].

Septic superficial thrombophlebitis


Septic superficial thrombophlebitis is a serious condition that can be lethal. The
following can occur:

Systemic sepsis, septicaemia, septic shock


Metastatic abscess formation
Embolic pneumonia, which has a high incidence of abscess formation and cavitation
Empyema
Pulmonary infarction
Endocarditis
Arteritis

[Feied and Handler, 2004b; Johnson, 2004; Scheld and Sande, 2005]

Prognosis
Aseptic superficial thrombophlebitis

Aseptic superficial thrombophlebitis usually a benign self-limiting disease.


Duration of symptoms is variable, but in uncomplicated superficial thrombophlebitis
symptoms of redness and tenderness usually resolve within 26 weeks, although the
thrombosed vein may be palpable and tender for months [Johnson, 2004].
If thrombophlebitis has occurred in a lower limb in a varicose vein, recurrence is likely
unless the varicose vein is excised [Johnson, 2004].
Prognosis will be determined by the development of DVT or other serious complications.
Thrombosis may present as a small lump days or weeks after an intravenous infusion has
been removed and may take months to completely resolve.

Septic superficial thrombophlebitis

Mortality can be high in suppurative superficial thrombophlebitis if untreated. In


one old study (from 1970) of 24 people, all 14 of those treated medically died, but of those
treated surgically, 7 survived and only 1 of the 3 deaths was attributable to suppurative
thrombophlebitis [Scheld and Sande, 2005].

Management issues
When should I consider the possibility of a DVT?

Always consider the possibility of a coexistent deep vein thrombosis (DVT)


[Mortimer and Burnand, 2004]. A DVT may be present with no clinical signs.
Extension of thrombophlebitis up the proximal part of the long saphenous vein in
the thigh to the sapheno-femoral junction has been found to be particularly associated with

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DVT by extension to the femoral vein through the sapheno-femoral junction [Lutter et al,
1991; Chengelis et al, 1996].
There is some evidence from small studies that a DVT is more likely if the person
does not have varicose veins. One study of 58 people (population not defined) with
superficial thrombophlebitis of the lower legs found that the prevalence of DVT in people
without varicose veins was 44% and with varicose veins was 2.6% [Bergqvist and
Jaroszewski, 1986]. A study of 60 people attending a private outpatient clinic found an
incidence of DVT in 8% of those with varicose veins but in 33% of those with no varicose
veins [Gorty et al, 2004].
Other risk factors that have been associated with DVT or PE in people with
superficial thrombophlebitis are:
o
Past history of DVT or venous thromboembolism
o
Bilateral involvement
o
Bed rest/recent immobilization
o
Male sex
o
Age greater than 60 years
o
Systemic infection
Co-existent malignancy, pregnancy, and taking combined oral contraception
should also be considered to be significant risk factors. We could find no studies that
have investigated the incidence of DVT specifically in people who have superficial
thrombophlebitis and one of these factors, but there is evidence from other populations that
they are associated with an increased risk of DVT.

[Lutter et al, 1991; Bounameaux and Reber-Wasem, 1997; Schonauer et al, 2003]

When should I suspect underlying disease?

Suspect underlying disease if thrombophlebitis occurs in a previously normal


superficial vein (i.e. not a varicose vein) that has not been subject to trauma and if
conditions that predispose to thrombosis (e.g. pregnancy, oral contraceptive pill use) have
been excluded [Messmore et al, 1991].
A hereditary thrombophilia (e.g. protein C or protein S deficiency, antiphospholipid
syndrome) should be suspected if there is a family history of thrombosis, or if superficial
thrombophlebitis is recurrent, or occurs at an early age [Samlaska and James, 1990a]. Seek
advice from a haematologist regarding possible tests to exclude a hereditary thrombophilia.
Migratory thrombophlebitis is associated with underlying malignancy, particularly
cancer of the pancreas, stomach, lung, breast, gallbladder, ovaries, prostate, and colon, and
with Behet's and Buerger's disease [Samlaska and James, 1990b; Ryan and Sinclair, 2003].
For more details regarding predisposing conditions, see What are the risk factors?

Who should I admit?

Always admit:
o
If there is suppurative thrombophlebitis, as the infected vein must be removed
surgically [Feied and Handler, 2004b; Scheld and Sande, 2005].
o
If there is clinical evidence of a deep vein thrombosis (DVT).
o
If chest pain or dyspnoea are present, as either may indicate pulmonary embolism.
Admit or arrange urgent hospital assessment if DVT is suspected. Particularly
suspect DVT if:
o
Thrombophlebitis is mid-thigh extending towards the sapheno-femoral junction. Duplex
scanning is advisable to determine the extent of thrombus propagation [Mottahedeh
and Da Silva, 2003; Leon et al, 2005].
o
If other risk factors are present, such as past history of DVT or venous
thromboembolism, bilateral involvement, recent bed rest or immobilization, or
involvement of a non-varicose vein (see What are the risk factors?).
There is conflicting opinion over whether DVT needs to be excluded in people with
superficial thrombophlebitis at sites other than the mid-thigh. Local guidelines should
be followed where they exist and clinical judgement used.
Septic thrombophlebitis will require admission for antibiotic treatment unless the
infection is mild.
o
Particularly consider the possibility of septic thrombophlebitis if there is a break in the
skin (e.g. with intravenous cannulation or drug abuse).
o
There is no guidance in the literature regarding criteria for admission. People who are
systemically unwell or with enlarged lymph nodes or tracking should always be
admitted but it should be remembered that even people with mild symptoms can
deteriorate rapidly.
o
Use clinical judgement, with special caution in high risk groups such as drug addicts
who may have unusual infections, including botulism, MRSA (methicillin-resistant
Staphylococcus aureus) and Streptococcus Group A.

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Consider referral for varicose vein surgery if symptoms persist or if extensive


varicosities are present.

How should I treat aseptic superficial thrombophlebitis?

There is a lack of data on how effective any of the medical treatments are for superficial
thrombophlebitis (see Supporting evidence) [Leon et al, 2005].
Uncomplicated superficial thrombophlebitis affecting venous tributaries is usually
treated symptomatically with:
o
Nonsteroidal anti-inflammatory drugs (NSAIDs)
o
Compression stockings on the legs
o
Paracetamol is an alternative analgesic for people who are intolerant of NSAIDs
Local heat. The use of local heat (e.g. a warm moist towel or flannel to the affected limb)
has been standard practice for years. Although there is no evidence for its use, some people
may find it helpful.
Treatment should continue until pain and redness have settled (usually within 26 weeks,
although the thrombosed vein may be palpable and tender for months).
Anticoagulants are not usually indicated for superficial thrombophlebitis. If deep vein
thrombosis is suspected, arrange for urgent referral. The use of anticoagulants for
thrombophlebitis are not recommended in primary care.
Encourage use of the affected arm or leg, and to continue usual daily activities. Leg
elevation is thought to improve venous blood flow and to reduce swelling. Bed rest is not
advised, as bed rest may increase the risk of deep vein thrombosis.
Consider referral for varicose vein surgery if extensive varicosities are present or if
symptoms persist, as ligation and stripping of the affected veins may be indicated
[Belcaro et al, 1999; Johnson, 2004]. Follow local guidelines and use clinical judgement.
Advise against standing for long periods of time and inactivity [Johnson, 2004].
Compression stockings. There is no evidence for the use of compression stockings and
there is conflicting advice in the literature. Follow local guidelines where they exist and use
clinical judgement. It is important to exclude arterial insufficiency. As thrombophlebitis is
quite a painful condition many people will find the use of Class 2 compression stockings
almost impossible and Class 1 stockings are a practical alternative.

How should I manage septic superficial thrombophlebitis?

Septic superficial thrombophlebitis is uncommon and will normally require admission


for antibiotic treatment unless mild. See Who should I admit?
The possibility of septic thrombophlebitis should be considered if there is a break in the
skin (e.g. with intravenous cannulation or drug abuse) although it can occasionally occur
spontaneously.
Treatment of septic superficial thrombophlebitis with antibiotics in primary care is
indicated only if the infection is mild.
The treatment of mild septic superficial thrombophlebitis is the same as that of cellulitis;
flucloxacillin or a macrolide such as erythromycin or clarithromycin may be used [McNulty,
Personal Communication, 2005].

Medicines management
What are the adverse effects of NSAIDS?

A full discussion on the contraindications, adverse effects, monitoring issues, and


interactions of nonsteroidal anti-inflammatory drugs (NSAIDs) is beyond the scope of this
guidance. For further information, see the CKS topic on Nonsteroidal anti-inflammatory
drugs (NSAIDs).
Consider patient comorbidity when prescribing NSAIDs; they commonly cause
gastrointestinal adverse effects, and can worsen asthma, hypertension, renal impairment,
and heart failure.
For people with thrombophlebitis who are at high risk of gastrointestinal adverse events, we
recommend the following options:
o
Use paracetamol instead of an NSAID if possible, or
o
Use a gastroprotective drug with a standard NSAID [NICE, 2001].
For advice on the management of dyspepsia due to NSAIDs, see the CKS topic on
Nonsteroidal anti-inflammatory drugs (NSAIDs).

Paracetamol

Paracetamol should be taken at regular intervals, rather than on an 'as required' basis.

Flucloxacillin

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Flucloxacillin has been associated with an increased risk of hepatic disorders,


namely hepatitis and cholestatic jaundice. The Committee on Safety of Medicines (CSM)
advises that hepatic reactions may occur up to 2 months after treatment with flucloxacillin
has stopped. Risk factors include treatment for more than 14 days and increasing age. The
dose and route of administration do not seem to affect the risk of hepatic disorders.

Macrolides

Erythromycin commonly causes gastrointestinal adverse effects, especially at higher


doses. If gastrointestinal adverse effects are known to occur, consider prescribing
clarithromycin instead.
Erythromycin and clarithromycin can increase the levels of certain other drugs
(e.g. theophylline, carbamazepine) and can potentiate the effects of warfarin.
If erythromycin or clarithromycin are taken with a statin, there is an increased risk of
myopathy.

Supporting evidence
To our knowledge, no adequately designed comparative trials have been performed addressing
the relative efficacy and safety of the various medical treatment options available for
thrombophlebitis.

What is the evidence for NSAIDs?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are thought to be useful in treating


superficial vein thrombosis because of their analgesic and anti-inflammatory properties.
However, there is little documented evidence to support their use and they are
recommended on the basis of expert opinion.
One pilot double-blind randomized trial (n = 427) compared tenoxicam (an NSAID available
in Canada similar to piroxicam), two different dosage regimens of enoxaparin (a low
molecular weight heparin), and placebo for 10 days in people with superficial
thrombophlebitis [Superficial Thrombophlebitis Treated By Enoxaparin Study Group, 2003].
All groups were also treated with compression stockings. The primary outcome measure was
deep venous thrombosis (defined as deep vein thrombosis, symptomatic pulmonary
embolism, or both). The secondary outcome measure was the combined endpoint of deep
venous thrombosis and/or superficial vein thrombosis recurrence or proximal extension.
o
By day 12, there was no statistically significant difference in the primary outcome
measure in any active treatment group compared with placebo. However, the incidence
of the secondary outcome measure was significantly less in all active treatment groups
compared with placebo (9.3% and 6.9% in the enoxaparin groups, 14.9% in the
tenoxicam group, and 30.6% in the placebo group). However, the difference in
incidence was mainly due to a reduction in the incidence of superficial vein events.
o
At 3-month follow-up, there was still a statistically significant difference in active
treatment groups compared with placebo.
o
There were no statistically significant differences in outcomes between the enoxaparin
and tenoxicam treated groups.
Topical NSAIDs: there are no good quality trials that compare the efficacy of topical NSAIDs
with the same NSAID given orally, with placebo or with paracetamol in people with
thrombophlebitis. One small, underpowered, poorly designed trial (n = 68) compared
piroxicam gel with placebo and piroxicam gel with heparinoid gel. Because of the flawed
methodology it is not possible to draw any conclusions from the trial [Bergqvist et al, 1990].

What is the evidence for anticoagulants?

The rationale for treating superficial thrombophlebitis with heparin or low molecular weight
heparin (LMWH) is the neutralization and inhibition of thrombin generation and the
prevention of thrombus extension and recurrence of thrombus [Kalodiki and Nicolaides,
2002]. Anticoagulation is not recommended unless the thrombus is large and extending
toward the sapheno-femoral junction (a relatively rare situation) [Wakefield, 1994].
One pilot double-blind randomized trial (n = 427) compared two different dosage regimens
of enoxaparin (a LMWH), tenoxicam (a nonsteroidal anti-inflammatory drug), and placebo
for 10 days in people with superficial thrombophlebitis [Superficial Thrombophlebitis Treated
By Enoxaparin Study Group, 2003]. All groups were also treated with compression
stockings. The primary outcome measure was deep venous thrombosis (defined as deep
vein thrombosis, symptomatic pulmonary embolism, or both). The secondary outcome
measure was the combined endpoint of deep venous thrombosis and/or superficial vein
thrombosis recurrence or proximal extension.
o
By day 12, there was no statistically significant difference in the primary outcome
measure in any active treatment group compared with placebo. However, the incidence
of the secondary outcome measure was significantly less in all active treatment groups
compared with placebo (9.3% and 6.9% in the enoxaparin groups, 14.9% in the

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tenoxicam group, and 30.6% in the placebo group). However, the difference in
incidence was mainly due to a reduction in the incidence of superficial vein events.
o
At 3-month follow-up, there was still a statistically significant difference in active
treatment groups compared with placebo.
o
There were no statistically significant differences in outcomes between the enoxaparin
and tenoxicam treated groups.
A small open randomized trial (n = 60) compared high-dose heparin (12,500 IU) with lowdose heparin (5000 IU) treatment for 4 weeks in people with acute thrombophlebitis of the
great saphenous vein in the thigh [Marchiori et al, 2002]. The outcome measure was the
incidence of thromboembolic complications (defined as asymptomatic deep vein thrombosis
and/or symptomatic thromboembolic events).
o
After 6-months' follow-up, the rate of thromboembolic complications was 20% (95% CI
7.7 to 38.6%) in the in the low-dose group and 3.3% (95% CI 0.07 to 17.2%) in the
high-dose group. Overall, there were 26 thromboembolic complications, but 19 of these
were superficial vein events (extension or recurrence of superficial thrombophlebitis).
o
Although the results suggest that high-dose heparin may be beneficial compared with
low-dose heparin, the confidence intervals overlapped and the results were of
borderline statistical significance (p = 0.05) using a one-sided test and non-significant
using a two-sided test (p = 0.10).

What is the evidence for compression stockings?

There are no good quality randomized controlled trials to support the use of compression
stockings in people with thrombophlebitis. However, it is standard practice to use them in
people with superficial thrombophlebitis, as it is thought that they reduce pain, improve
venous blood flow, and reduce the risk of further thrombosis. Which class of stocking or
whether a full leg or below knee stocking should be used is not stated in the literature
[Messmore et al, 1991; Wakefield, 1994].
We found one open randomized trial (n = 562) that assessed the efficacy of elasticated
stockings (class of stocking not specified) in people with superficial thrombophlebitis
affecting varicose veins [Belcaro et al, 1999]. In this study, one group used elasticated
stockings, a second group used elasticated stockings and had early surgery (simple ligation
or complete stripping), and a third group used elasticated stockings with prophylatic
anticoagulation and delayed surgery.
o
Over a 6-month period, the incidence of deep vein thrombosis ranged from 3.15.3%,
with no statistically significant difference among the treatment groups.
o
Those treated with compression alone or compression plus saphenous ligation were
more likely to have extension of the superficial thrombophlebitis at 36 months' followup.

What is the evidence for hot compresses?

There are no trials that assess the efficacy of hot compresses or the application of heat to
treat thrombophlebitis. Hot compresses are recommended on the basis of expert opinion
[Messmore et al, 1991; Wakefield, 1994].

What is the evidence for antibiotics?

There is no evidence for the use of antibiotics for the treatment of aseptic superficial
thrombophlebitis. If septic superficial thrombophlebitis is suspected then admission for
antibiotic treatment is generally advised, unless the infection is mild. See How should I
manage septic superficial thrombophlebitis?

References
NHS staff in England can link, free of charge, from references to the full text journal
articles by clicking on [NHS Athens Full-text]. You will need an NHS Athens password to
access these resources. Click here for Athens registration.
All references with links to [Free Full-text] are freely available online to users in
England and Wales. This includes the full text of Department of Health papers and Cochrane
Library reviews.
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