Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)
Authors: Ay Cihan , Vormittag Rainer , Dunkler Daniela , Simanek Ralph , Chiriac Alexandru-Laurentiu , Drach Johannes , Quehenberger Peter , Wagner Oswald , Zielinski Christoph , Pabinger Ingrid 
Published: October 2019

Abstract
Venous thromboembolism (VTE) is a frequent complication of cancer, which represents a major cause of morbidity and mortality in cancer patients. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. D-Dimer is a global indicator of coagulation activation and fibrinolysis and is frequently elevated in cancer patients, even without thrombosis. The measurement of D-dimer levels is a widely applied test in the diagnostic work-up of patients with suspected VTE. Prospective observational studies have shown that D-dimer levels have a predictive value for the risk of recurrence in non-cancer patients after the discontinuation of oral anticoagulant treatment. Whether testing for D-Dimer at diagnosis of cancer would be useful for prediction of cancer-associated thrombosis, is not elucidated because up to now appropriately designed prospective studies have not yet been carried out. Therefore, we have assessed D-Dimer levels in cancer patients as risk predictor for VTE and provide a report from the ongoing prospective observational CATS, which was initiated in October 2003. Patients with newly diagnosed cancer or progression of disease that had neither chemotherapy within the last three months, nor radiotherapy nor surgery within the last two weeks were recruited and followed prospectively. Occurrence of VTE and information on the patients’ anti-cancer-treatment within the follow up period were recorded. Observation ended with occurrence of VTE, death or after 2 years. VTE has always been confirmed by imaging. D-Dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan Meier and Cox regression analysis were applied for statistical calculation. Data on 821 patients with cancer (370 women/451 men, median age [IQR]: 62 [53–68] yrs) were available for analyses. Patients were followed for a median observation time of 454 days. Main tumour entities were malignancies of the breast (n=132), lung (n=119), upper (n=35) and lower gastrointestinal tract (n=106), pancreas (n=46), kidney (n=22) and prostate (n=101). Furthermore, 102 patients had high-grade glioma, 94 lymphomas, 17 multiple myeloma and 47 other tumour types. During the observation period VTE occurred in 62 patients (24 female/38 male, median age [IQR]: 60 [50–66] yrs). Elevated levels of D-Dimer (cut-off level 1.44 μg/ml, representing the 75th percentile of the total study population) [hazard ratio (HR): 2.4, 95% CI 1.4–4.0], surgery [HR: 2.3, 95% CI 1.0–5.3] and radiotherapy [HR: 2.3, 95% CI 1.2–4.4] were statistically significant risk factors for VTE in multivariate analysis including D-Dimer, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of developing VTE after 6 months was 11.2 % in patients with D-Dimer levels above and 4.2 % in those below the 75th percentile (p=0.003). In conclusion, cancer patients with elevated D-Dimer levels have an approximately 3-fold increased risk for future occurrence of VTE. High levels of D-Dimer independently predict VTE in these patients and D-Dimer measurement at diagnosis of cancer would help identify patients at increased risk for VTE.