Background D-dimers are used in conjunction with clinical probability scores in the assessment of venous thromboembolism (VTE), and they are elevated in other conditions, including malignancy, infection and arrhythmias. High levels of D-dimers in VTE are associated with adverse outcomes, including increased mortality. Their significance in patients without VTE has not previously been established.

Aims To establish the clinical significance of elevated D-dimer levels in patients without VTE.

Methods This prospective study included 2263 patient episodes of suspected deep vein thrombosis, which were excluded radiologically. Patients were followed up for survival and adverse events for a median of 22 months.

Results D-dimer levels greater than 4000 ng FEU/ml (4.9% of patients), and greater than 8000 ng FEU/ml (1.8%) were associated with a reduced overall survival. D-dimer levels greater than 8000 ng FEU/ml and age over 60 years were independent poor prognostic factors for overall survival (p<0.001.). D-dimer levels greater than 8000 ng FEU/ml were associated with an increased incidence of malignancy (p=0.003).

Conclusions This study provides evidence of very high D-dimer levels in patients with cancer who do not have VTE. This suggests that elevated D-dimer levels in patients with VTE and malignancy are not solely due to presence of thrombus. High D-dimer levels in malignancy are likely to reflect the biology of the underlying tumour, with higher levels observed in breast, prostate and bowel cancers.