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Diagnosing deep vein thrombosis: the latest

Richard Kent
Technical author
specialising in medical ­diagnostics and healthcare issues

Venous thromboembolism is the third most common cardiovascular disease after ischaemic syndromes and stroke in the Western world.(1) Clots can form in major blood vessels and may migrate and become lodged elsewhere. Deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins, usually of the lower limbs. This is different to the formation of clots in the superficial varicose veins in the legs, which is much less serious. In around 10% of DVT cases the clot moves to the lungs causing a pulmonary embolism (PE). One in every 100 people who develop DVT dies.(2)
Common symptoms of DVT include pain, redness, tenderness and swelling of the affected limb. These symptoms can also be attributed to other disorders, such as infective cellulitis, ruptured Baker's cyst, fracture and haematoma, so diagnostic tests are required to confirm an accurate diagnosis.

Travel sickness?
Many factors are believed to contribute to the formation of a thrombus. As far back as 1954, travel, or more specifically spending long periods seated in a cramped position, was identified as a factor. The link between travelling for long periods in cramped conditions and DVT is still reported on a regular basis, especially as long-haul travel increases and the rise in popularity of budget airlines with limited seating space continues.

Risk factors
Despite the impression newspapers may give, many other factors have been identified that are also high-risk factors for the development of DVT.(2) First, the risk increases greatly with age. There is an incidence rate of less than 1 in 3,000 in those under the age of 40 years. Over the age of 80 this rate has reached 1 in 500.(3) Other risk factors include:

  • Previous personal or family history of DVT.
  • Abnormality of clotting factors.
  • Malignancy.
  • Hormone treatment, including the oral ­contraceptive pill and oestrogen-containing ­hormone replacement therapy.
  • Pregnancy.
  • Recent major surgery or injury, particularly ­affecting the lower limbs or abdomen.
  • Recent immobilisation for a day or more.

By checking how many of the above high-risk categories patients fall into and how many typical symptoms of DVT are exhibited, a model has been developed that classifies patients as having high, intermediate or low risk of developing DVT. This pretest probability model has been used in diagnostic algorithms to reduce the number of diagnostic tests required on patients with suspected DVT.(4,5)
The symptoms caused by DVT can vary greatly. Some patients exhibit no symptoms until a PE is formed. Other patients suffer pain and swelling of the affected leg. These same symptoms could also have many other causes, so clinical diagnosis is essential. The two main methods for this involve ultrasonography or venography.

Developing diagnostics
Contrast venography was once considered the gold standard for establishing the diagnosis of DVT. However, this procedure is invasive, isn't always technically possible, and carries with it a small risk of an allergic reaction or venous thrombosis. Ultrasonography is now the standard noninvasive diagnostic method for DVT. It has high specificity for proximal DVT, but until recently it had much lower (even as low as 75%) specificity for symptomatic calf vein thrombosis.(4) However, improvements in technology have made the latest equipment, in the hands of a skilled operator, at least as accurate as venography for confirming a diagnosis of DVT. Ultrasound has the additional benefit of being able to differentiate conditions that often resemble DVT, such as ruptured Baker's cyst and muscle tear/haematoma.
While these methods provide accurate results and should be used to confirm DVT, they are either invasive or not widely available, or they are associated with their own risks. Dedicated equipment is required, and this may be limited to use within a hospital by highly trained ­specialists. As a result, blood-based assays have become an important firstline diagnostic tool. As diagnostic ­technology has developed, they allow for quick and inexpensive exclusion of patients who have not suffered a thrombotic event. This means that further testing and unnecessary treatment can be avoided for many patients.
Prominent in this development has been the introduction of D-dimer assays. D-dimer is one of the families of fibrin fragments, which form and circulate in the bloodstream for several days following a thrombotic event. These cross-linked derivatives of fibrin are degraded by plasmin during a clotting event. In normal circumstances this forms a natural part of the wound healing process, but when clots form as the result of an underlying disease D-dimer becomes a useful marker of thrombotic events. However, presence of D-dimer can also be caused after operations or by malignancy or pregnancy, meaning that a positive result does not prove DVT.
A variety of D-dimer assays are available that can be performed by various medical professionals in different locations. Importantly, D-dimer assays have also become established as point-of-care tests. These rapid tests provide results in less than 10 minutes using simple handheld equipment. No instrumentation is required, and test storage is normally at room temperature. Qualitative results make interpretation straightforward.
D-dimer point-of-care tests have been widely evaluated in studies of patients with DVT and PE. Using D-dimer assays to screen suspected DVT cases, it is possible to identify patients who definitely don't have DVT. Many can be spared from having to undergo invasive procedures such as venography, angiography and lung scans, which can cause unnecessary trauma. If screening is performed early, using a point-of-care test at a community clinic, for example, a patient may not need to go to a hospital at all. It has been estimated that as many as 70-75% of people presenting with the symptoms of DVT are subsequently shown to be free of thrombosis. Current commercially available point-of-care testing assays are easy to use and straightforward to interpret.

References

  1. AGEN Biomedical website. D-dimer reference centre. Available from URL: http://www.agen.com.au
  2. DoH. Advice on travel-related DVT. Available from URL: http://www.doh. gov.uk/blood/dvt/index.htm
  3. NHS Direct. Available from URL:http://www.nhsdirect.nhs.uk
  4. Tovey C, Wyatt S. BMJ 2003;326:1180-4.
  5. Turpie A, Chin B, Lip G. BMJ 2002;325:887-90.