Diagnostic and Prognostic Implications of Elevated D-Dimers in Cancer Patients with Venous Thromboembolism

Background
Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a frequent and serious complication in cancer patients due to tumor-related hypercoagulability and treatment effects. D-dimer testing is commonly used to exclude VTE in the general population because of its high sensitivity. However, in oncologic patients, D-dimer levels are often elevated due to various non-thrombotic factors such as inflammation or tumor burden, which lowers specificity and limits its utility. Despite current guideline recommendations against using D-dimer testing for VTE diagnosis in cancer patients, extreme values—either very high or very low—may still provide meaningful diagnostic and prognostic insights. This study aims to evaluate the performance of D-dimer testing in this high-risk population, aiming to identify thresholds that retain clinical relevance.

Methods
This retrospective study aimed to evaluate the diagnostic and prognostic utility of D-dimer levels in cancer patients presenting to the emergency department with suspected PE or DVT. A total of 526 patients were included: 83 with a final adjudicated diagnosis of PE, 69 with DVT, and 374 in whom VTE was excluded, serving as the control group.

Results
For identifying VTE, D-dimer levels demonstrated a positive predictive value of 96% (95% confidence interval [CI], 85–99%) at concentrations ≥9.9 mg/L and a negative predictive value of 100% at ≤0.6 mg/L (95% CI, 97–100%). At the conventional rule-out threshold of 0.5 mg/L, D-dimer testing showed excellent sensitivity (100%) with a moderate specificity of approximately 65%. An optimized cut-off of 4.9 mg/L increased specificity to 95% for detecting life-threatening VTE but reduced sensitivity to 64%. Over a median follow-up period of 30 months, elevated D-dimer levels were significantly associated with VTE recurrence (p = 0.0299) and with all-cause mortality in both cancer patients with VTE (p < 0.0001) and those without VTE (p = 0.0008).

Conclusions
Despite current guidelines advising caution in interpreting D-dimer levels in cancer patients, very high concentrations—exceeding ten times the upper reference limit—may provide meaningful diagnostic and prognostic information. While low D-dimer levels remain reliable for ruling out VTE, markedly elevated levels could aid in risk stratification and long-term outcome prediction.