Plasma D-dimer levels greater than 5,000 ng/ml are encountered in a number of conditions beyond venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for COVID-19 infection. The implications of abnormal levels are less clear for COVID-positive patients with baseline elevation in plasma D-dimer levels. This study reviews the occurrence of plasma D-dimer levels >5,000 ng/ml and investigates the clinical significance of this finding prior to the onset of the COVID-19 pandemic.