How Productive is the D-Dimer for Chest Pains and Covid-19?

D-dimers are cleavage products of fibrin that occur during plasmin-mediated fibrinolysis of blood clots. In the emergency department, D-dimer tests are broadly used as an excellent non-invasive triage biomarker in patients, which measurement represents a valuable and cost-effective tool in the differential diagnosis of acute chest pain including the main life-threatening entities: acute coronary syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic and prognostic values of D-dimer testing in acute coronary syndrome is of less priority, increases of D-dimers are frequently found in venous thromboembolism and acute aortic syndromes, especially acute aortic dissection.

Laboratory evaluation

D-dimer levels can be assessed by microplate enzyme-linked immunosorbent assay, enzyme-linked immunofluorescence assay, whole-blood cell agglutination, or latex agglutination tests. The sensitivity, specificity, and negative predictive value of D-dimer tests depend on the kind of used test, the cutoff value, and the kind of assumed disease. Cutoff levels are influenced by the kind of test used and may differ between different laboratories. D-dimer levels are associated with the amount of clotted blood. Highest levels are reached in massive venous thromboembolism and after cardiovascular arrest.

Influence of D-Dimers on ACS

Acute myocardial ischemia is caused by thrombotic occlusion of coronary arteries, implicating that D-dimer levels should be raised in focal coronary thrombosis. Whereas troponin is a highly sensitive and specific parameter for myocardial injury, elevation is measurable not until 3-4 hours after onset of symptoms. By contrast, D-dimer propose earlier rise than common markers of cardiac injury. It has been demonstrated that increased D-dimer levels may serve as an independent diagnostic marker for myocardial infarction with an increase in diagnostic sensitivity of the electrocardiogram and clinical history plus D-dimer.

Value of D-Dimer Measurement in PE

D-dimers have been shown to be highly sensitive in venous thromboembolism. Owing to the fact that deep vein thrombosis and pulmonary embolism often occur at the same time and up to 50% of patients with deep vein thrombosis have clinically inapparent pulmonary embolism, D-dimer levels can be used similarly in patients with deep vein thrombosis and pulmonary embolism. Therefore, the D-dimer test as a fast and cost-effective method is recommended in suspected pulmonary embolism.

D-Dimers in Aortic Dissection and other Aortic Syndromes

The term acute aortic syndrome includes different conditions ranging from an intramural hematoma to typical aortic dissection, together characterized by a disruption of the structural integrity of the aortic wall with subsequent initiation of coagulation. Apart from clinical presentation, imaging methods, and other biomarkers, D-dimers might be of diagnostic as well as prognostic value. It has been shown that a positive D-dimer test has a sensitivity of about 97%, a specificity of 56%, a positive predictive value of about 60%, and a negative predictive value of up to 96%.

Role of D-Dimer During the Pandemic

COVID-19 has caused health equipment shortages worldwide, and the allocation of scarce resources is problematic and presents with many ethical problems. To provide the most benefit to COVID-19 patients, there is an increasing need to better allocate these scarce resources. Raised D-dimer level is considered a poor prognostic feature for COVID-19 patients. More recently, according to a pooled analysis study, increased D-dimer values were frequently found in patients with a severe COVID-19, suggesting that this biomarker has a promising potential for determining mortality. Few studies have also reported an increased risk of mortality in COVID-19 patients with elevated on-admission D-dimer levels.

Baseline D-dimer measurements and adverse events. aOR indicates adjusted odds ratio.

Trajectory of D-dimer during the first 21 d of hospitalization. Patients are stratified by (A) acute kidney injury, (B) critical illness, (C) thrombosis, and (D) all-cause mortality.

COVID-19 at 4 hospitals within a large health system in New York City, 1823 (76%) had evidence of elevated D-dimer above the laboratory-specific upper limit of normal at hospital presentation and 2049 (86%) had an elevated D-dimer at any point during the hospitalization before discharge. Outcomes of patients with elevated D-dimer at the time of admission were particularly poor, with 45% critically ill, 20% with thrombosis, and 43% with acute kidney injury. D-dimer level was independently associated with these outcomes after multivariable adjustment for demographics, clinical characteristics, and other biomarkers that we have previously shown are associated with adverse outcomes. In contrast, individuals without an elevated D-dimer at presentation were more likely to be discharged without developing a critical illness.

Conclusions

D-dimer as a marker for activation of coagulation system is a fast and cost-effective parameter used in emergency medicine in the discrimination of acute thoracic pain. Furthermore, D-dimer level on admission has a promising prognostic value for predicting all-cause mortality of COVID-19 patients. Despite the differences in threshold values across the studies, there was a roughly fivefold increase in all-cause mortality for patients with elevated D-dimer levels on admission compared to normal level.

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