High D-Dimer Levels at Presentation in Patients with Venous Thrombosis Is a Marker of Poor Overall and Event Free Survival.

The role of D-dimer estimation along with clinical probability scoring is well established in the diagnosis of deep venous thrombosis. The issue of predictive value of quantitative D-dimer analysis to various clinical outcomes are being addressed. We have studied here the effect of quantitative D-dimer level at presentation in patients with deep venous thrombosis on overall survival (OS), event free survival (EFS), extent of thrombosis and occurrence of malignancy.

Methods

This study included 608 (F: 305; M: 303) consecutive patients from the prospectively maintained database of patients with venous thrombosis at a University Teaching Hospital, between February 2001 and May 2005. All patients underwent an Doppler ultrasound examination to confirm the diagnosis and determine the extent of venous thrombosis. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. Thrombosis recurrence was always confirmed by Doppler ultrasound examination. All Patients with thrombosis received standard treatment with low molecular weight heparin and Warfarin. OS and EFS were estimated by the Kaplan-Meier method. For the purpose of EFS analyses, death, thrombosis recurrence, pulmonary embolism and malignancy occurrence were all considered as events. Cox regression analysis was subsequently used to explore the independent effect of variables that showed a significant influence on OS or EFS by univariate analysis. P values < 0.05 were considered significant.

Results:

Median age at diagnosis was 64yrs (Range: 16–96 yrs) and median follow up was 22 months (Range: 0–51 months). Median D-dimer level at presentation was 2.3 mg/ml (Range: 0.1–46.3 mg/ml). 341 (58.3%) patients had above knee thrombosis, 244 (41.7%) patients had below knee venous thrombosis and 14 (2.3%) patients had upper limb thrombosis. 132 (22.2%) patients either had or developed malignancy during the study period. Recurrence of thrombosis was observed in 28 patients (4.6%). Both univariate and multivariate analysis confirmed the independent poor prognostic impact of age > 60 yrs, D-dimer > 8mg/ml and above knee thrombosis on OS (P = 0.001, 0.007 & 0.045, respectively) and EFS (P = 0.032, 0.008 & 0.003, respectively). D-dimer > 8mg/ml was also associated with occurrence of malignancy (P value: <0.001) and above knee venous thrombosis (P < 0.001). Neither elevated D-dimer nor above knee thrombosis were predictive of recurrence, whereas age < 60 yrs at diagnosis was associated with increased risk of recurrence of thrombosis (P = 0.006).

Conclusions:

Elevated D-dimer at presentation was associated with decreased event free survival and overall survival in patients with venous thrombosis. High D-dimer at presentation was a marker for underlying malignancy in patients with thrombosis and was also a predictor of extensive thrombosis. Further studies are warranted to ascertain, whether alternative anticoagulation regimens like prolonged anticoagulation or more intensive anticoagulation negates the adverse impact of high D-dimer at presentation in patients with venous thrombosis.