What's New in Critical Illness and Injury Science? D-Dimer point of care testing for thromboembolic emergencies presenting to the emergency department.

The degradation of fibrin clots by plasmin leads to the formation of a mixture of cross-linked fibrin degradation products called D-dimer. Presence of D-dimer in plasma is a biomarker indicating degree of thrombin turnover and activation of the coagulation pathway.[1]

The levels of D-dimer can be elevated in various conditions. Lippi et al. showed that some of the common causes where patients can present with elevated D-dimer levels are infection, venous thromboembolisms (VTE), syncope, heart failure, trauma and cancer. D-dimer testing has been introduced to improve the diagnostic process and also to reduce the number of unnecessary referrals for leg compression ultrasonography.[2]

In general, commercial D-dimer assays for blood have a high sensitivity of 95% but have a poor specificity, making it difficult to prove the presence of deep vein thrombosis (DVT) or pulmonary embolism (PE) instead of another clotting complication. However, the negative predictive values (NPVs) are nearly 100% accurate, with negative D-dimer test results of indication of a lack of DVT or PE. Hence, the main clinical application of D-dimer assay is to safely rule out DVT, PE, or disseminated intravascular coagulation.[13]

Currently the more commonly used D-dimer ELISA has a turn-around time of approximately 40 min, however the preanalytic time of getting a sample from an emergency department (ED) to the laboratory can delay the total turn-around time dramatically.[45]

In recent years, there have been a few studies that have analyzed the role of D-dimer in point of care testing. von Lode et al. developed a 10 min, noncompetitive immunofluorometric assay for D-dimer in citrated whole blood and plasma. They compared the D-dimer levels for patients who were diagnosed with DVT and/or PE (Group A, n = 77) with various outpatients with other diseases (Group B, n = 174). The sensitivity, specificity, NPVs and positive predictive values were 98.7% 64.4%, 99.1% and 55.1% for Group A and 92.2%, 81.0%, 95.9%, and 68.3% Group B, respectively. The high sensitivity and NPV suggested that rapid immunofluorometric assay for D-dimer could be a valuable tool for rapid exclusion of VTE in the ED. In combination with clinical testing, further testing for setting a cut-off would enable this is as a stand-alone point of care test.[6]

Subsequently, Lewandrowski et al. compared whole blood D-dimer test with a conventional laboratory testing for D-dimer by assessing the impact on the length of stay (LOS) in the ED. They found that the implementation of point of care testing resulted in a significant decrease in the mean and median ED LOS and concluded that there was a possible change from hospital admission toward discharge or a short stay admission to observe the study patients.[5] A recent prospective, single center study by Sen et al. from Newcastle University has compared the diagnostic accuracy of a POC quantitative method with the standard laboratory testing, where patients with suspected DVT and PE were included. They observed that the point of care testing was sufficiently accurate to be used as a screening tool in the ED, eventually leading to a profound clinical significance, and possibly decreasing the time to manage critically ill cases as well as decreasing the LOS by 84%.[7]

In another study of 577 prospectively identified consecutive primary care patients suspected with DVT, all patients underwent 5 point of care D-dimer testing. Out of the 5 point of care tests, 4 were quantitative, and one was qualitative, after which the referencing was done with ultrasonography. It was observed that all the five tests showed a high NPV (98%). However the sensitivities varied (0.91 for the qualitative test and 0.99 for the Vidas D-dimer test). Although the specificity for the qualitative test was the highest (0.64), further diagnostic testing was still required for a final diagnosis of DVT. It was also noticed that clinical decision in conjunction with the qualitative test prevented 50% referrals and missed only 1.4% of DVT cases during follow-up.[8]

In the studies discussed above, point of care D-dimer tests has demonstrated a high diagnostic accuracy, aiding in a safe and cost-effective exclusion of DVT. Future diagnostic studies looking at a combined quantitative and qualitative assessment of these tests in the domain of primary care will provide a deeper insight towards the role of D-dimers in point of care testing.