The clinical significance of ultra-high D-dimer levels

OBJECTIVE: Plasma D-dimer levels >5000 ng/mL are encountered in a number of conditions other than venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for coronavirus disease 2019 (COVID-19) infection. The implications of abnormal levels are less clear for patients diagnosed with COVID-19 with a baseline elevation in plasma D-dimer levels. In the present study, we reviewed the occurrence of plasma D-dimer levels >5000 ng/mL and investigated the clinical significance of this finding before the onset of the COVID-19 pandemic. METHODS: Inpatient records for a 4-year period were screened for laboratory results of plasma D-dimer levels >5000 ng/mL. The patient data were reviewed for the clinical identifiers commonly associated with elevated plasma D-dimer levels, including VTE, cancer, sepsis, pneumonia, other infection, bleeding, and trauma. The patients were then categorized into groups stratified by the plasma D-dimer level to allow for comparisons between the various clinical diagnoses. RESULTS: A total of 671 patients were included in the present study. VTE was the most common diagnosis for patients with a plasma D-dimer level >5000 ng/mL, followed by cancer and pneumonia. Multiple clinical diagnoses were present in 61% of the patients. No clear cause for the ultra-high plasma D-dimer level could be identified in 11.3% of the patients. Among the patients lacking a clinical diagnosis at discharge, mortality was 24% in the 5000- to 10,000-ng/mL group, 28.6% in the 10,000- to 15,000-ng/mL group, and 75% in the >15,000-ng/mL group. CONCLUSIONS: VTE, cancer, and pneumonia were frequently present when ultra-high plasma D-dimer levels were encountered, and mortality was high when the levels were >15,000 ng/mL. The results from our study from a pre–COVID-19 patient population suggest that ultra-high plasma D-dimer levels indicate the presence of severe underlying disease. This should be considered when using the plasma D-dimer level as a screening tool or prognostic indicator for COVID-19 infection.