Elevated D-Dimer Level Is a Predictor of Poor Survival Even in Patients without Venous Thromboembolism (VTE).

Use of D-dimer levels along with clinical probability scores in the diagnosis of venous thrombosis is well established. Recently it has been shown that high quantitative D-dimer levels at presentation are predictor for poor survival and underlying malignancy in patients with VTE. Do quantitative D-dimer levels in patients without VTE have a similar predictive role?

Materials and Methods

This study included 2263 (F: 1518; M: 745) consecutive patient episodes from the prospectively maintained database of patients without venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients with suspected venous thrombosis underwent a Doppler ultrasound examination to rule out venous thrombosis. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review.

Statistical analysis was carried out using SPSS 13.0 for Windows and GraphPad InStat ® Version 3.06 for Windows software’s. Overall survival (OS) was estimated by the Kaplan-Meier method. Cox regression analysis by forward Likelihood Ratio was subsequently used to explore the independent effect of variables that showed a significant influence on OS.

Results

Median age at diagnosis was 69 yrs (range: 18–105 yrs). Median D-dimer level was 1000ug FEU/ml (range: 300–35500ug FEU/ml). 1165 patients (51.7%) had a D-dimer level of >1000ug FEU/ml and 40 (2%) had a D-dimer level of >8000ug FEU/ml at presentation. 1472 patients (65.4%) were aged above 60 years. Median follow up was 22 months (range: 0–65 months). D-dimer level >1000ug FEU/ml, >4000ug FEU/ml and >8000ug FEU/ml were associated with decreased overall survival (Log rank test: p value: 0.002, < 0.001 and <0.001 respectively). Age>60 yr is also associated with decreased overall survival (Log rank test: p value: <0.001). D-dimer >8000ug FEU/ml and age>60yr were an independent poor prognostic factor for overall survival on Cox regression analysis (p value: <0.001). 27.5% of patients with a D-dimer level >8000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.003). 17% of patients with a D-dimer level >4000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.04). 12.4% of patients with a D-dimer level >1000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.02).

Conclusions

This study show elevated D-dimer levels at presentation in patients without venous thrombosis is a marker of poor survival and a predictor for underlying malignancy. We have previously shown that D-dimer >8000ug FEU/ml is a predictor for poor survival and underlying malignancy in patients with proven venous thrombosis. This suggests heightened fibrinolytic activity in the absence or presence of established venous thrombosis is associated with poor prognosis. Further studies are warranted to establish in different medical conditions the presence or absence of increased fibrinolysis and impact on clinical outcome.