D-dimer

Following history, evaluation of risk factors and clinical examination, the D-dimer test is the most immediately available investigation used in the diagnostic strategy for DVT in the ED. This test is vulnerable to mis-use (with potential patient harm) if its role is misunderstood.

The test detects fibrin fragments from clot degradation with a high sensitivity when used in appropriately risk-stratified patients with suspected VTE: a negative D-dimer assay in this population results in a 3 month incidence of subsequent VTE of approximately 0.5%.

However, its specificity is poor: D-dimer levels may be raised in any clinical condition in which clot turnover (clot formation and subsequent degradation) is increased.

Such conditions are common and include:

• Infection
• Following trauma
• Following haemorrhage
• Cancer
• Post-surgery

D-dimer assay

The assay also returns increasingly positive with advanced age, irrespective of the potential presence of any of these predisposing factors.

A further important issue is the type of D-dimer assay used: a number of different D-dimer assays are in use throughout the UK, with varying levels of sensitivity and specificity.  Each test employs a different monoclonal antibody sensitive to a different part of the D-dimer molecule:

• Latex agglutination assays – older tests less accurate and no longer recommended
• enzyme linked immunosorbent assays (ELISA) – accurate but time consuming
• rapid ELISA (VIDAS)  – accurate and rapid version of above
• SimpliRed D-dimer – sensitive for proximal DVT, high negative predictive value³

D-dimer levels remain detectable for 7 days after initial clot formation. Testing outside this time may result in a false negative result. The presence of small clot load, particularly in the distal venous system, may provide too small a D-dimer level for a positive result. This may not be of major clinical concern, however, since there is no universal agreement whether isolated distal DVT requires treatment.

The role of D-dimer

It is critical that the result of a D-dimer assay is interpreted in light of the overall clinical picture and with knowledge of the locally used assay’s characteristics. The assay is always used for its sensitivity (i.e. ability to rule out the diagnosis of DVT) rather than its specificity (i.e. ability to rule it in). This means that, in the appropriate clinical context, it is possible to definitively exclude a diagnosis of DVT and discharge a patient. It is not possible to definitively make the diagnosis: if the D-dimer assay is positive, further investigation is required.

So the crucial question is: “in which individual patients is the D-dimer test going to be useful in ruling out a diagnosis of DVT?” The answer to this question depends on the pre-test probability of DVT which, in turn, is determined by clinical risk stratification.

The major exception to this principle is pregnant / post-partum women in whom the risk of DVT and/or PE is universally high; there is no role for D-dimers in the investigation of these patients who, if the diagnosis is suspected, require definitive imaging.

Another group of patients that are being increasingly recognised as being at high risk of DVT is the intravenous drug abuser; in particular, they are at risk of septic DVT. This group should also be considered at high risk of DVT and investigated accordingly.

The baseline ‘normal’ D-dimer level increases with age and in order to avoid false positive results and subsequent over investigation, NICE now suggest an age adjusted D-dimer test threshold should be considered. This means for patients aged 50 and over, their threshold level should equate to either 10x their age, or 5x their age, depending on the assay for D-dimer used locally. This should be confirmed with your laboratory prior to use of this rule.⁴

Learning bite

All pregnant / post-partum women with suspected DVT or PE are at high risk and need definitive imaging; there is no role for a D-dimer assay.