Improved use of D-dimer to rule out pulmonary embolism
D-dimer is a breakdown product of the protein fibrin that forms the basis of a blood clot. The concentration of D-dimer in the bloodstream rises when there is a blood clot in a deep vein in the leg (deep vein thrombosis) or after fragments from the clot have been carried to the lung causing chest pain and breathlessness (pulmonary embolism). However, raised D-dimer results are also found in many other conditions including recent surgery, trauma, infection, liver disease, kidney disease, cancer and pregnancy.
In patients who are clinically assessed to be at low risk of having had a pulmonary embolism (PE), there is a consensus that a D-dimer test result below a fixed cut-off value can rule out a PE as the cause of their chest symptoms. Further complex investigations such as computed tomography and anticoagulant treatment are then unnecessary. However, the test is less useful in elderly patients due to the fact that D-dimer levels increase with age. For example, the fixed cut-off has been shown to safely rule out pulmonary embolism in 60% of patients aged less than 40 but in only 5% of patients over 80.
Doctors from four European hospitals analysed data from patients who had been admitted to their emergency departments with suspected pulmonary embolism. The diagnosis was confirmed in 416 (24%) of the 1721 patients after sequential diagnostic investigations and a three month follow-up. They derived D-dimer cut-off values that increased linearly from the age of 50, and then validated them retrospectively against data from a total of more than 3000 patients who had been clinically assessed to have a low probability of pulmonary embolism. The results, published in the BMJ on 30 March 2010, showed that the diagnosis could have been safely ruled out in between 25 and 30% of older low risk patients. The authors said that a prospective trial to validate age-adjusted cut-offs was needed before clinical implementation.
Between 2010 and 2013 a prospective trial was carried out on 3346 patients presenting to 19 emergency departments in Belgium, France, the Netherlands and Switzerland. Those with D-dimer values below the age-adjusted cut-off did not undergo computed tomography or receive anticoagulant treatment. Success or failure of the strategy was assessed after three months follow-up with a patient questionnaire by telephone interview, contact with the general practitioner and case note review of those readmitted to hospital. All suspect events of thrombosis were adjudicated by three independent experts. The results of the trial were reported in the Journal of the American Medical Association on 19 March 2014. In 673 patients aged over 75 with a low clinical probability of pulmonary embolism, the fixed cut-off ruled out pulmonary embolism in only 43 (6.4%) while an age-adjusted cut-off ruled out 200 (29.7%) with no false negative results.