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.

Summary Qualitative d‐dimer results, together with clinical probability scores, are well established in the diagnosis of venous thromboembolism (VTE). The predictive value of quantitative d‐dimer levels for various clinical outcomes in VTE patients is not fully understood. d‐dimer levels obtained at presentation were analysed in 699 (360 men; 339 women) VTE patients for survival and occurrence of malignancy. Patients were followed for a median of 23 months. 17·2% patients had a d‐dimer level >8000 ng FEU/mlat presentation, which was associated with decreased overall survival (OS) (P < 0·001) and event‐free survival (EFS) (P < 0·001). 25·4% patients had malignancy and 4% subsequently developed malignancy following VTE. 29·9% of patients with VTE and malignancy had a d‐dimer level >8 mg/l when compared with 13·4% of patients with VTE without malignancy (P < 0·001). 50% of patients who developed subsequent malignancy following VTE had a presentation d‐dimer >8000 ng FEU/mlas compared with 13·3% of patients with VTE with out malignancy (P = 0·009). In conclusion, d‐dimer >8000 ng FEU/ml at presentation in patients with VTE is a marker of poor OS, EFS and underlying malignancy. Consideration of screening for malignancy is recommended in patients with VTE with a presentation d‐dimer >8000 ng FEU/ml and age >60 years.

Association between VTE and cancer has been recognised for over a century. The incidence of occult or overt malignancy in patients with thrombosis is 7–26%. VTE has been shown to impart poor prognosis in patients with cancer and cancer also adversely impacts on the survival of patients with VTE. It is desirable to identify patients with thrombosis at increased risk of malignancy or those with minimal risk, thus avoiding unnecessary investigations. We propose here a predictive model using age and quantitative D-dimer level at presentation along with site of thrombosis. Materials and Methods This study included 696 (M: 358; F: 338) consecutive patients from the prospectively maintained database of patients with venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients underwent a Doppler ultrasound examination to confirm the diagnosis and determine the extent of venous thrombosis. At presentation, 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 Thrombosis recurrence was always confirmed by Doppler ultrasound examination. All Patients with thrombosis received standard treatment with low molecular weight heparin and warfarin. Statistical analysis was carried out using SPSS 13.0 for Windows software. A logistic multivariate regression model was fitted using complete data records from 621 patients with an indicator variable for a subsequent cancer as the response and age, the natural logarithm of the quantitative D-dimer level and the site of the thrombosis as explanantory variables. The fitted model was validated using an additional set of independent data. Results The model correctly identified the VTE patients without malignancy in 473 out of 480 cases (98.5% accuracy). But the model was ineffective in identifying VTE patients with malignancy (13 out of 141; 9% accuracy). The area under the receiver operating characteristic (ROC) curve was 0.72, indicating that the test developed for predicting cancer for the model data was reasonably good. Our model shows that below a predicted probability of 0.10 less than 5% of the patients actually developed cancer (9/190) whereas for a predicted probability of 0.19 less than 10% of patients actually developed cancer (27/276). In the validation dataset of 93 patients with VTE, the model correctly identified the number of patients without malignancy in 72 out of 73 cases (98.6% accuracy). One-sample binomial tests revealed that there was no significant difference in the number VTE patients with cancer between the model and the validation dataset for the predicted probabilities of 0.10 and 0.19 (p-values of 0.650 and 0.246 respectively). Conclusions This suggests that our model is useful for identifying patients at minimal risk of developing cancer with VTE. This predictive model has been validated by an independent dataset demonstrating reproducibility. This model will enable a focused and a cost-effective strategy of screening for a malignancy in patients with 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 &gt;1000ug FEU/ml and 40 (2%) had a D-dimer level of &gt;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 &gt;1000ug FEU/ml, &gt;4000ug FEU/ml and &gt;8000ug FEU/ml were associated with decreased overall survival (Log rank test: p value: 0.002, &lt; 0.001 and &lt;0.001 respectively). Age&gt;60 yr is also associated with decreased overall survival (Log rank test: p value: &lt;0.001). D-dimer &gt;8000ug FEU/ml and age&gt;60yr were an independent poor prognostic factor for overall survival on Cox regression analysis (p value: &lt;0.001). 27.5% of patients with a D-dimer level &gt;8000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.003). 17% of patients with a D-dimer level &gt;4000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.04). 12.4% of patients with a D-dimer level &gt;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 &gt;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.