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Need to know - venous thromboembolism

The usefulness of D-dimer testing, best choices for anticoagulation and implications for contraception are covered by haematologists Dr Andrew Retter and Dr Beverley Hunt in answer to GP Dr Kathryn Griffith’s questions.

The usefulness of D-dimer testing, best choices for anticoagulation and implications for contraception are covered by haematologists Dr Andrew Retter and Dr Beverley Hunt in answer to GP Dr Kathryn Griffith's questions.

1. What is the predictive value of the various clinical features in a patient with a swollen painful leg? Which features make a diagnosis of a venous thromboembolism event (VTE) more likely?

41185934Leg pain, warmth and swelling are clinical signs found in some patients with a deep vein thrombosis (DVT). Patients are at high risk if they have a previous history of a venous thromboembolism (VTE), malignancy, recent surgery, or immobility. Some 80% of DVTs are asymptomatic and therefore the clinical index of suspicion should always remain high.

The differential diagnosis of a DVT includes:

• muscle strain

• cellulitis

• ruptured Baker's cyst

• venous insufficiency

• lymphangitis.

The Wells scoring system available right is a method of assessing the pre-test probability of a DVT. A prior history of VTE is the single strongest risk factor for a repeat VTE. Occasionally individuals with a significant thrombophilia can present with a DVT as a teenager or young adult without an obvious precipitating factor, and their DVT will often get missed initially because they are considered too young.

2. What proportion of patients with a DVT might have occult carcinoma?

Patients with either a clinical diagnosed or occult cancer are at increased risk of a VTE. The largest prospective study of acute VTE (RIETE) has more than 17,000 patients1. Of these, 16% had cancer diagnosed before VTE or during admission. However, occult cancer was only detected in 1.2%. Those with occult cancer had a higher rate of bleeding and recurrent DVT. They also had a higher mortality at three months of follow-up – 20% versus 5.4% mortality. Those aged 60 to 75, with idiopathic DVT, with bilateral DVT and/or with anaemia were at increased risk of occult cancer. Patients with these risk factors should have a careful history taken and be examined to elicit any occult malignancy. This should act as the starting point to guide further investigation. It is unclear, however, that early detection does improve the prognosis of occult cancers.

3. How should the D-dimer be used in primary care to rule out DVT or PE?

The D-dimer is an assay used to detect fibrin degradation products. It is best used in conjunction with a clinical risk prediction score such as the Wells score.

When a D-dimer is negative in a patient with a low pre-test probability, the chance of missing a VTE is less than 1%. The patient can be reassured and discharged without anticoagulation.

A positive D-dimer indicates that VTE is a possibility and imaging of the legs is the next step. However, D-dimers are also positive in patients with malignancy, trauma, infection, infarction, pregnancy and after recent surgery.

4. What proportions of patients with a positive D-dimer test do not have a VTE?

The proportion with a positive D-dimer depends on how robust the initial screening is beforehand. A positive result is difficult to interpret in patients with malignancy, trauma, infection, infarction, pregnancy or recent surgery. If the index of suspicion is high we may proceed straight to ultrasound.

A possible diagnosis of VTE should always be aggressively pursued in high-risk individuals. The D-dimer test comes into its own for its negative predictive value – for instance in a low-risk patient with a negative D-dimer, one can be reassured there is a very low risk of DVT and there is no need to proceed to imaging.

5. How do you decide who to anticoagulate after an ultrasound of the leg vein?

Current guidelines advise immediate full-dose anticoagulation with a low molecular weight heparin (provided there are no contraindications, such as renal failure) while awaiting the results of imaging. If the imaging is negative, anticoagulation can be stopped – unless a strong clinical suspicion remains, in which case continued low molecular weight heparin is suggested until a second ultrasound is performed a week later. If a Doppler ultrasound shows a positive thrombus, the patient should be switched to warfarin therapy and the low molecular weight heparin stopped when the INR is greater than 2. Venography should be used in patients with previous DVT, as ultrasound is unreliable.

6. Are all patients with a DVT screened for a PE, and how many will have asymptomatic PE?

PE and DVT represent the spectrum of one disease. About 30% or patients who have a DVT have evidence of small clinically asymptomatic PE using sensitive lung imaging.

Also, approximately 80% of patients who present with a PE have imaging evidence of a DVT. If no DVT can be found it is most likely that it has embolised entirely. We perform oxygen saturation monitoring and take a history, specifically questioning for shortness of breath, pleuritic chest pain, cough and haemoptysis. A chest radiograph is non-diagnostic but useful to exclude other lung pathology. If the history is suggestive or the patient hypoxic they proceed to have a ventilation-perfusion scan or a CT pulmonary angiogram.

7. What is the optimum duration of anticoagulation for a DVT? What if the DVTs are recurrent? Do you vary your INR range according to the collective factors in a patient rather than just first DVT?

Current recommendations are six weeks for a DVT confined to the calf, and three months warfarin for those with their first proximal DVT or PE. A recent study showed that there was little advantage of increasing the duration of anticoagulation from three to six months2. Certainly, six months' warfarin increases the bleeding risk.

Patients who suffer recurrent VTE will require long-term anticoagulation.

Initially all patients should start with a target INR range of 2 to 3. The range is only increased to 3-4 if patients suffer a repeat VTE while their INR is therapeutic between 2 to 3.

Patients with apparently unprovoked VTEs or a VTE in an unusual place have a thrombophilia screen. If either antithrombin deficiency or an antiphospholipid antibody is detected then the use of indefinite anticoagulation is discussed with the patient, in view of the high risk of recurrence.

8. Thrombolysis has a routine use in arterial thrombosis. Does it have a role in DVT?

Thrombolysis is theoretically attractive as it could reduce the risk of thrombus extension, and possibly post-phlebitic syndrome. But thrombolysis has never been proven to be beneficial in clinical trials. Many patients will have contraindications and there persists the possibility that it will cause life-threatening intracranial haemorrhage. Therefore, VTEs are not routinely thrombolysed at present.

9. I have an intravenous drug misuser with a DVT put on daily low molecular weight heparin for six months, as she was judged too erratic for warfarin. There is a big cost and logistic implication. Do you ever do this?

Yes, this is good alternative standard practice. These patients are usually able to self-inject, and often have such poor venous access that it is difficult to obtain blood to monitor warfarin therapy.

In this patient population the risk of bleeding associated with warfarin can be high. Low molecular weight heparin remains the most effective compromise to minimise bleeding risk and maintain anticoagulation. Although low molecular weight heparin is more expensive than warfarin, the overall cost remains low, as monitoring is not required.

10. I am going to New Zealand soon. Do you have any advice to reduce my risk of VTE? What about the issue of low-dose aspirin?

The risk of VTE with long-haul travel has been overstated. Any individual at risk of VTE should be advised to have soft drinks on the flight to prevent dehydration and to regularly flex their ankles to contract their calf muscles, and occasionally walk around. Compression stockings may be of benefit if they fit well. Ill-fitting stockings can cause a superficial thrombophlebitis. Those with post-phlebitic syndrome should wear their grade II compression stockings.

High-risk patients can consider taking a single dose of low molecular weight heparin subcutaneously – dalteparin 5,000u, enoxaparin 40mg or tinzaparin 3,500 or 4,500u – just prior to departure if they are not on warfarin. There is no evidence that aspirin will reduce the risk of traveller's thrombosis and with the risk of gastric irritation, it is not recommended3.

The major cause of traveller's thrombosis seems to be prolonged immobility. The term SIT – seated immobility syndrome –has been coined to cover this.

11. Is there an increased risk of VTE associated with progesterone?

Although not completely devoid of risk, the progesterone-only pill, Depo-Provera, or intrauterine devices are the preferred choice of contraception in patients who have had a previous VTE or an inherited thrombophilia and wish to avoid pregnancy. It is important to consider that pregnancy itself carries a six-fold increased risk of thrombosis.

12. What is the presence of inherited or acquired thrombophilia and what should be the screening method for this in patients who may be at risk? What do you say to someone who has a negative screen but a suggestive family history?

Thrombophilia is the inherited or acquired predisposition to develop venous thromboembolism. Patients are screened for both acquired and inherited defects. Thrombophilia testing is indicated in cases of an unprovoked VTE or when a patient suffers a thrombosis at an unusual site. Approximately 50% of Caucasian patients with an unprovoked VTE will have a genetic risk factor identified on screening. Most of the common polymorphisms such as Factor V Leiden and prothrombin 20210 are only present in the Caucasian population, so there is a lower rate of detection in non-white ethnic groups. The subsequent risk of recurrent VTE depends on the type of defect, (acquired or inherited) and in particular whether the defect is homozygous or heterozygous or compound heterozygous.

Some 50% of patients will not have a thrombophilia identified. This may be because the patient has an as-yet unknown defect or their risk factor was transient and resolves by the time of testing. If the screen is negative the patient will require three months' anticoagulation after a first VTE. If the patient has recurrent VTE they require long-term anticoagulation.


Thrombophilia screening is being questioned, especially in situation such as women with a family history of DVT wishing to start the pill. Practically in this situation a negative thrombophilia screen does not help because we do not know whther the proband had an identifiable thrombophilia. If the patient is identified with Factor V Leiden or prothrombin 20210, by far the commonest thrombophilias, then the risk of thrombosis on the pill with these thrombophilias is still less than the risk of thrombosis during pregnancy.

Any patient who has antithrombin deficiency or is homozygous or a compound heterozygote for two or more clotting defects and has a VTE should receive lifelong anticoagulation. As the management is individualised and requires a specific risk benefit analysis, we recommend these patients are referred for specialist testing and follow-up.

Dr Andrew Retter is a specialist registrar in haematology at Guy's and St Thomas' Trust in London.

Dr Beverley Hunt is a consultant haematologist at Guy's and St Thomas' Trust in London.

Competing interests

Dr Retter None declared

Dr Hunt has received restricted travel grants to attend conferences from Bayer and sanofi-aventis and has received lecture fees from sanofi-aventis in the past.

What I will do now What I will do now

Dr Griffith reflects on the answers to her questions
• I'll bear in mind that the patients most at risk of a DVT are those who have had a previous VTE, recent surgery, known malignancy or immobility.
• The Wells scoring system is useful to predict the probability of pulmonary embolism and interpret the results of blood and radiological testing.
• I'll remember that a negative D-dimer test helps rule out VTE and patients with a positive test should have imaging.
• When there is a high clinical suspicion of VTE patients are given low molecular weight heparin until the diagnosis is ruled out or if confirmed until INR reaches 2.
• It's useful to know that low molecular weight heparin is also used long term in special circumstances such as an IV drug user.
Dr Kathryn Griffith is a GP in York

Wells Scoring System for DVT Wells Scoring System for DVT DVT thp vte

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Readers' comments (1)

  • I was looking for the d-dimmers range and more explanation on how it is deemed negative or positive

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