A venous thrombus most often occurs in the deep veins of the legs or pelvis and is then called a deep vein thrombosis (DVT). The clot may dislodge and travel to the lungs to cause a pulmonary embolism.
A DVT can be very difficult to diagnose but early recognition and appropriate treatment can save many lives. A thrombus either arises spontaneously or is predisposed by such conditions as surgery, trauma or prolonged bed rest. They usually form in the deep veins of the lower limbs but may extend higher and into the pelvic veins. The close relationship between DVT and pulmonary embolism (PE) is such that the term venous thromboembolism (VTE) is often used to cover both conditions.
- DVT has an annual incidence of about 1 in 1,000 people.
- Major risk factors for VTE include a prior history of DVT, age over 60 years, surgery, obesity, prolonged travel, acute medical illness, cancer, immobility, thrombophilia and pregnancy.
- One study found that 50-70% of patients had readily identifiable risk factors.
- Two thirds of patients with proven PE have no symptoms of DVT and, in one third of cases, without an autopsy it is impossible to find the original site of a DVT.
- Autopsy studies demonstrate that approximately 80% of all cases of DVT and PE remain undiagnosed, even when they are the immediate cause of death.
Risk factors for VTE
Other risk factors:
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The clinical diagnosis of DVT can be very difficult. Many DVTs progress to PE without DVT being clinically apparent. In those with classic clinical signs, only about 50% have DVT. Classical features are from obstruction to venous drainage:
- Limb pain and tenderness along the line of the deep veins.
- Swelling of the calf or thigh (usually unilateral). Involvement of the iliac bifurcation, the pelvic veins, or the vena cava produces leg oedema that is usually bilateral.
- Distension of superficial veins.
- Increase in skin temperature.
- Skin discolouration (erythema or occasionally purple or cyanosed).
- A palpable cord (hard, thickened palpable vein).
- Low-grade fever (said to be rare but perhaps not sought often enough).
- Homans' sign: positive when there is pain or resistance in the calf or popliteal region with abrupt passive dorsiflexion of the patient's foot at the ankle while the knee is fully extended. Homans' sign in not specific and so not helpful in diagnosis.
Cellulitis adds to the problem:
- Severe signs of DVT can resemble cellulitis.
- Secondary cellulitis may develop with primary DVT.
- Primary cellulitis may be followed by a secondary DVT.
- Superficial thrombophlebitis may hide an underlying DVT.
Other diagnoses should be considered, including:
- Superficial thrombophlebitis.
- Post-thrombotic syndrome.
- Peripheral oedema, heart failure, cirrhosis, nephrotic syndrome.
- Venous or lymphatic obstruction.
- Arteriovenous fistula and congenital vascular abnormalities.
- Ruptured Baker's cyst.
Assessment and investigations
- If a patient presents with signs or symptoms of DVT, carry out an assessment of general medical history and a physical examination to exclude other causes.
- Offer patients in whom DVT is suspected and with a likely two-level DVT Wells' score (see below) either:
- a proximal leg vein ultrasound scan carried out within 4 hours of being requested and, if the result is negative, a D-dimer test (see below); or
- a D-dimer test and an interim 24-hour dose of a parenteral anticoagulant (if a proximal leg vein ultrasound scan cannot be carried out within 4 hours) and a proximal leg vein ultrasound scan carried out within 24 hours of being requested.
- Repeat the proximal leg vein ultrasound scan 6-8 days later for all patients with a positive D-dimer test and a negative proximal leg vein ultrasound scan.
- Offer patients in whom DVT is suspected and with an unlikely two-level DVT Wells' score a D-dimer test and, if the result is positive, offer either:
- a proximal leg vein ultrasound scan carried out within four hours of being requested; or
- An interim 24-hour dose of a parenteral anticoagulant (if a proximal leg vein ultrasound scan cannot be carried out within four hours) and a proximal leg vein ultrasound scan carried out within 24 hours of being requested.
- Diagnose DVT and treat patients with a positive proximal leg vein ultrasound scan.
Consider an alternative diagnosis in patients with:
- An unlikely two-level DVT Wells' score and a negative D-dimer test, or a positive D-dimer test and a negative proximal leg vein ultrasound scan.
- A likely two-level DVT Wells score and a negative proximal leg vein ultrasound scan and a negative D-dimer test, or a repeat negative proximal leg vein ultrasound scan.
Use a scoring system such as the Wells' diagnostic algorithm to assess pre test probability:
Wells' diagnostic algorithmBecause of the unreliability of clinical features, several diagnostic scoring systems have been validated whereby patients are classified as having a high, intermediate or low probability of developing DVT, based on history and clinical examination.
Score one point for each of the following:
- Active cancer (treatment ongoing or within the previous six months, or palliative).
- Paralysis, paresis or recent plaster immobilisation of the legs.
- Recently bedridden for three days or more, or major surgery within the previous 12 weeks, requiring general or regional anaesthesia.
- Localised tenderness along the distribution of the deep venous system (such as the back of the calf).
- Entire leg is swollen.
- Calf swelling by more than 3 cm compared with the asymptomatic leg (measured 10 cm below the tibial tuberosity).
- Pitting oedema confined to the symptomatic leg.
- Collateral superficial veins (non-varicose).
- Previously documented DVT.
The risk of DVT is likely if the score is two or more, and unlikely if the score is one or less.
- These are specific cross-linked products of fibrin degradation and are raised in patients with VTE. Sensitivity is high but specificity poor.
- High concentrations occur in other disorders, such as malignancy and pregnancy and in other conditions where clots form, as after surgery. The investigation of VTE in pregnancy is fraught with many difficulties.
- Several D-dimer assays are available, eg ELISA tests or SimpliRED whole blood agglutination test suitable for near patient testing. Some evidence suggests that D-dimer should be measured after the end of the anticoagulation period, to assess the risk of re-thrombosis.
Plethysmography involves recording of changes in the size of the limb, due to tissue fluid or pooled blood in the veins. Techniques include photoplethysmography (absorption of light by haemoglobin), strain gauge and electrical impedance (change in calf size or electrical impedance of skin during and after occluding venous outflow).
Imaging can be by venography, by two-dimensional ultrasound, or by magnetic resonance imaging.
- All these tests are most sensitive when DVT is symptomatic, when thrombus causes complete venous outflow obstruction and when the clot extends into the upper thigh.
- False negatives are highest when the thrombus is solely below the knee or above the groin, when obstruction is incomplete and when the patient is asymptomatic.
The choice of definitive test may depend upon local protocols, as none is perfect.
- Duplex ultrasound is the initial investigation of choice in nearly all patients with suspected DVT.
- Its reliability is dependent upon the skill of the user.
- It may miss a non-occlusive thrombus in up to 40% of cases involving the iliac or pelvic veins.
- Major axial veins of the lower limb are well displayed.
- Compression ultrasonography is increasingly being used early in the investigative process.
- Magnetic resonance venography and CT venography may be useful adjuncts.
- Contrast venography has long been "the gold standard" of diagnosis for DVT.
- An intravenous catheter is placed in a dorsal vein of the foot and contrast medium is infused into the vein.
- A tourniquet around the leg occludes the superficial veins and forces contrast into the deep veins.
- A positive result tends to be conclusive but a negative result is less reassuring. It is time-consuming and requires much technical skill to obtain good results.
- It is highly invasive and has substantial morbidity and mortality, unlike the other diagnostic tests for DVT.
- Up to 10% of patients have new thrombosis shortly after a negative venogram. This may be because it missed the original DVT or because intravenous contrast can trigger thrombosis by causing endothelial injury.
- Extravasation of contrast material into the dorsum of the foot may cause sloughing of tissue.
- Anaphylactoid reactions to contrast material occur in 3% of patients and can cause death.
- Offer all patients diagnosed with unprovoked DVT or PE, who are not already known to have cancer, the following investigations for cancer: a physical examination (guided by the patient’s full history), CXR, blood tests (FBC, serum calcium and LFTs) and urinalysis.
- Consider further investigations for cancer, with an abdomino-pelvic CT scan (and a mammogram for women), in all patients aged over 40 years with a first unprovoked DVT or PE who do not have signs or symptoms of cancer based on initial investigation.
- Consider testing for antiphospholipid antibodies in patients who have had unprovoked DVT or PE if it is planned to stop anticoagulation treatment.
- Consider testing for hereditary thrombophilia in patients who have had unprovoked DVT or PE and who have a first-degree relative who has had DVT or PE if it is planned to stop anticoagulation treatment.
Refer people who are likely to have DVT for same-day assessment and management (local protocols may vary).
- Offer a choice of low molecular weight heparin (LMWH) or fondaparinux to patients with confirmed proximal DVT or PE, taking into account comorbidities and contra-indications, with the following exceptions:
- For patients with severe renal impairment or established renal failure (estimated glomerular filtration rate <30 ml/min/1.73 m2), offer unfractionated heparin (UFH) with dose adjustments based on the activated partial thromboplastin time (APTT), or LMWH with dose adjustments based on an anti-Xa assay.
- For patients with an increased risk of bleeding consider UFH.
- Start the LMWH, fondaparinux or UFH as soon as possible and continue it for at least five days or until the international normalised ratio (INR) is 2 or above for at least 24 hours, whichever is longer.
- Offer LMWH to patients with active cancer and confirmed proximal DVT or PE, and continue the LMWH for six months. At six months, assess the risks and benefits of continuing anticoagulation.
- Offer a vitamin K antagonist (VKA) to patients with confirmed proximal DVT or PE within 24 hours of diagnosis and continue the VKA for three months. At three months, assess the risks and benefits of continuing VKA treatment.
- Consider extending the VKA beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding.
- Rivaroxaban is recommended by NICE as an option for treating DVT and preventing recurrent DVT and PE after a diagnosis of acute DVT in adults.
- Consider catheter-directed thrombolytic therapy for patients with symptomatic iliofemoral DVT who have symptoms of less than 14 days’ duration, good functional status, a life expectancy of one year or more and a low risk of bleeding.
- Provide patients who are having anticoagulation treatment with an ‘anticoagulant information booklet’ and an ‘anticoagulant alert card’ and advise them to carry the ‘anticoagulant alert card’ at all times.
- Offer below-knee graduated compression stockings with an ankle pressure greater than 23 mm Hg to patients with proximal DVT a week after diagnosis or when swelling is reduced sufficiently and if there are no contra-indications. Advise patients to continue wearing the stockings for at least two years. Stockings need to be worn only on the affected leg or legs.
- Offer temporary inferior vena caval filters to patients with proximal DVT or PE who cannot have anticoagulation treatment, and remove the inferior vena caval filter when the patient becomes eligible for anticoagulation treatment.
- Consider inferior vena caval filters, for patients with recurrent proximal DVT or PE despite adequate anticoagulation treatment, only after considering alternative treatments such as increasing target INR to 3-4 for long-term high-intensity oral anticoagulant therapy, or switching treatment to LMWH.
- When a patient presents with a DVT, try to identify if there is an obvious cause, eg immobilisation or operation.
- If no cause is apparent and the patient is aged under 45, look for thrombophilia.
- If the patient is aged over 45, think of cancer.
- Many individuals who have a first episode of DVT or PE will have a recurrent event.
- Risk of recurrence may be reduced by the use of compression stockings.
- Death occurs in approximately 6% of DVT cases and 12% of PE cases within one month of diagnosis. Long-term outcome tends to be good if it is not associated with malignancy.
- May develop after a DVT due to damage to the deep veins and their valves.
- May cause minor skin changes, chronic pain or swelling, hyperpigmentation and leg ulceration.
- Affects 20-40% of patients after DVT of the lower limb and can have a significant impact on quality of life.
- Risks associated with the syndrome include older age, obesity, a history of previous ipsilateral DVT, iliac-femoral location of the current thrombosis, failure to recover promptly from the acute symptoms, and insufficient quality of oral anticoagulant therapy.
- There is a low risk of post-thrombotic syndrome in patients with asymptomatic DVT.
See separate related article Prevention of Venous Thromboembolism.
Further reading & references
- Venous Thromboembolism and Hormonal Contraception, Royal College of Obstetricians and Gynaecologists (September 2010)
- Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital, NICE Clinical Guideline (January 2010)
- Prevention and management of venous thromboembolism, Scottish Intercollegiate Guidelines Network - SIGN (December 2010)
- Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines, European Society for Medical Oncology (2011)
- Venous thromboembolic diseases, NICE Clinical Guideline (June 2012)
- Pulmonary embolism; NICE CKS, February 2011
- Ageno W, Agnelli G, Imberti D, et al; Risk factors for venous thromboembolism in the elderly: results of the master registry. Blood Coagul Fibrinolysis. 2008 Oct;19(7):663-7.
- Nijkeuter M, Ginsberg JS, Huisman MV; Diagnosis of deep vein thrombosis and pulmonary embolism in pregnancy: a systematic review. J Thromb Haemost. 2006 Mar;4(3):496-500. Epub 2005 Dec 23.
- Palareti G, Legnani C, Cosmi B, et al; Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost. 2002 Jan;87(1):7-12.
- Madhusudhana S, Moore A, Moormeier JA; Current issues in the diagnosis and management of deep vein thrombosis. Mo Med. 2009 Jan-Feb;106(1):43-8; quiz 48-9.
- Venous thromboembolism (treatment and long term secondary prevention) - rivaroxaban, NICE Technology Appraisal Guideline (July 2012)
- Goldhaber SZ, Bounameaux H; Pulmonary embolism and deep vein thrombosis. Lancet. 2012 May 12;379(9828):1835-46. Epub 2012 Apr 10.
- White RH; The epidemiology of venous thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):I4-8.
- Prandoni P, Kahn SR; Post-thrombotic syndrome: prevalence, prognostication and need for progress. Br J Haematol. 2009 May;145(3):286-95. Epub 2009 Feb 13.
- Persson LM, Lapidus LJ, Larfars G, et al; Asymptomatic Deep Venous Thrombosis is Associated with a Low Risk of Post-thrombotic Syndrome. Eur J Vasc Endovasc Surg. 2009 May 29.
|Original Author: Dr Laurence Knott||Current Version: Dr Colin Tidy||Peer Reviewer: Prof Cathy Jackson|
|Last Checked: 31/08/2012||Document ID: 2030 Version: 32||© EMIS|
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