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In patients where thrombus has been excluded, does a high d-dimer result indicate an underlying malignancy?

Three Part Question

In a [Patient with a suspected DVT but negative doppler US], does [a high D-Dimer result] suggest an [underlying malignancy]?

Clinical Scenario

A 65 year old lady with no history of DVT/PE presents with acute onset unilateral calf swelling/tenderness. There is no history of trauma, recent surgery, and no infective symptoms. She is investigated with a D-dimer blood test which comes back at 8000 ng FEU/ml and undergoes a doppler US which is negative. What is the evidence to suggest an underlying malignancy?

Search Strategy

Medline using OVID interface, 1966 to December 2011.
({d-dimer} OR {d-dimer} AND ({malign*} OR {cancer} LIMIT to human and English

Search Outcome

823 results of which 2 were relevant, but one of which was a case study so not included.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
L Knowlson et al.
2263 episodes (2016 patients) of suspected DVT and positive D-dimer but negative Doppler US.Prospective studyEmergence of malignancy over mean of 22 months27.5% of patients with >8000 ng FEU/ml went on to have a diagnosis of malignancy. 17% of patients with >4000 ng FEU/ml had malignancy. 9.3% of patients with <1000 ng FEU/ml had a diagnosis of malignancy.Patients not investigated for PE as a separate cause of raised D-dimer. No standardised follow-up but reliant on incidental re-presentation. Patients with known malignancy not excluded or differentiated in this study.


Although further studies are needed to confirm links between D-dimer results and sub-clinical malignancy, this paper suggests a correlation between high D-dimer results and malignancy.

Clinical Bottom Line

Patients with high D-dimer levels but no evidence of thrombosis, should be re-assessed by a thorough history and examination looking for malignancy. Specifically this includes breast, prostate, bowel, gynaecological, and lung cancers. This information should then be used to guide any further investigation or follow up.


  1. L Knowlson et al Elevated D-dimers are also a marker of underlying malignancy and increased mortality in the absence of venous thromboembolism Journal of Clinical Pathology 2010; 63: 818-822