From the Guidelines
D-dimer levels are commonly elevated in patients with malignancy due to multiple mechanisms related to cancer's effects on the coagulation system, including the production of tissue factor and cancer procoagulants, and the release of inflammatory cytokines that stimulate endothelial cells to express adhesion molecules and procoagulant factors 1.
Causes of Raised D-Dimer in Malignancy
The causes of raised D-dimer in malignancy can be attributed to several factors, including:
- Cancer cells directly activating the coagulation cascade, leading to increased fibrin formation and subsequent fibrinolysis, which generates D-dimer fragments
- Tumors releasing inflammatory cytokines that stimulate endothelial cells to express adhesion molecules and procoagulant factors, further enhancing coagulation activation
- Many cancer patients developing a hypercoagulable state known as Trousseau syndrome, characterized by increased risk of venous thromboembolism (VTE) and elevated D-dimer levels
- Tumor-associated macrophages and neutrophils contributing to this process by releasing neutrophil extracellular traps (NETs) that promote thrombosis
Specific Tumor Types and D-Dimer Levels
Specific tumor types, particularly pancreatic, gastric, and brain cancers, are associated with higher D-dimer levels 1. The extent of disease also matters, with metastatic cancers typically showing higher D-dimer levels than localized disease.
Limitations of D-Dimer as a Standalone Marker
While elevated D-dimer in cancer patients may indicate increased thrombotic risk, it has limited specificity as a standalone marker and should be interpreted alongside clinical findings and other laboratory tests 1.
Importance of Accurate D-Dimer Reporting
Accurate D-dimer reporting is crucial in cancer patients, as it can help identify those at increased risk of thrombotic events 1. However, the lack of standardization in D-dimer assays and reporting mechanisms can lead to confusion and potentially misleading data interpretation.
From the Research
Causes of Raised D-Dimer in Malignancy
- Elevated D-dimer levels are associated with underlying malignancy and increased mortality in the absence of venous thromboembolism 2
- High D-dimer levels are likely to reflect the biology of the underlying tumor, with higher levels observed in breast, prostate, and bowel cancers 2
- Extremely elevated D-dimer levels are uniquely associated with severe disease, mainly including venous thromboembolism, sepsis, and/or cancer 3
- The prevalence of cancer is high in patients with extremely elevated D-dimer levels, with 29% of patients having a diagnosis of cancer 3
Association with Cancer Prognosis
- High D-dimer levels are associated with poor prognosis in cancer patients, with increased mortality risk and reduced overall survival 4
- The univariate hazard ratio of D-dimer for mortality is 1.5, indicating a significant association between high D-dimer levels and increased mortality risk 4
- D-dimer levels can be used as a prognostic marker for overall survival and mortality risk in cancer patients 4
Relationship with Venous Thromboembolism
- Cancer-associated venous thromboembolism is a significant concern, with a high risk of recurrent VTE despite anticoagulant therapy 5, 6
- D-dimer levels are not significantly associated with recurrent VTE in cancer patients, whereas baseline P-selectin levels are a significant predictor of recurrent VTE 6
- The risk of recurrent VTE is high in cancer patients, with 9.4% of patients developing recurrent VTE in one study 6