Longitudinal analysis of hemostasis biomarkers in cancer patients during antitumor treatment.

UNLABELLED: ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease. BACKGROUND: Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients. OBJECTIVES: As there are almost no data on longitudinal changes, we aimed to evaluate those in the present prospective observational study during chemotherapy and the course of disease. PATIENTS/METHODS: Patients with cancer of the brain (n = 39), lung (n = 41), colon (n = 15) or pancreas (n = 17) were included before initiation of antitumor therapy. Blood samples for determination of factor VIII, thrombin peak height, D-dimer, F1 + 2 , fibrinogen and soluble P-selectin (sP-selectin) were drawn on a monthly basis. The study endpoints were death, VTE occurrence, or completion of the study period. RESULTS: Overall, 546 blood samples of 112 patients were analyzed. D-dimer and sP-selectin levels were significantly higher in patients with distant metastasis than in those without. Patients with complete remission had significantly lower levels of F1 + 2 , D-dimer and fibrinogen. Peak height thrombin levels showed a decrease over time in all tumor types. Levels of biomarkers behaved differently in the various tumor types. Patients who developed VTE (n = 14) showed increasing levels of FVIII, sP-selectin, and D-dimer. At the last blood sampling time-point before VTE occurrence, in 13 patients the D-dimer level was above the median, and in seven of these patients it was even above the 75th percentile; however, the individual course was highly variable. Regarding survival, steadily increased FVIII, sP-selectin and D-dimer levels were associated with higher mortality. CONCLUSIONS: Hemostatic parameters show an association with disease state, prognosis, and the risk of VTE, not only at diagnosis, but also during the course of antineoplastic treatment.

Factor V Leiden mutation increases the risk for venous thromboembolism in cancer patients - results from the Vienna Cancer And Thrombosis Study (CATS).

BACKGROUND: Patients with cancer are at an increased risk for venous thromboembolism (VTE). The risk varies markedly in different patient populations. Factor V (FV) Leiden is the most common genetic risk factor for VTE, and the impact of FV Leiden on cancer-associated thrombosis is not yet fully elucidated. OBJECTIVE: To study the impact of FV Leiden on the risk of thrombosis in cancer patients. METHODS: In the prospective observational Vienna Cancer And Thrombosis Study (CATS), 982 patients were included and were followed until occurrence of VTE or death, for a maximum period of 2 years. FV Leiden was determined by genotyping at inclusion. Main outcome measures were symptomatic or lethal objectively confirmed VTE. RESULTS: Of the 982 patients, FV Leiden was diagnosed in 72 (7.3%, 70 were heterozygous and 2 were homozygous). Ten of 72 (13.9%) patients with FV Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without FV Leiden. In multivariate analysis that included age, sex, different tumor types, tumor stage, newly diagnosed vs. recurrence of disease, and the treatment modalities, the hazard ratio was 2.0 (95% confidence interval 1.0-4.0). In Kaplan-Meier analysis, the probability for development of VTE was 13% in those with and 5.7% in those without FV Leiden after 6 months; after 1 year, the corresponding risks were 15% and 7.3%. CONCLUSIONS: FV Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients and could therefore be used for individual risk assignment.

Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients.

Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities. We investigated the association of eight different cytokines with venous thromboembolism (VTE) and prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a prospective study, includes patients with newly diagnosed tumour or disease progression. Patients with an overt infection are excluded. Study end-points are VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels were measured using the xMAP technology developed by Luminex. Among 726 included patients, no associations between IL levels and VTE were found, with the exception of a trend for IL-1ß and IL-6 in pancreatic cancer. Elevated levels of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1·07, 95% confidence interval (CI) = 1·027-1·114, P = 0·001, IL-8 (HR = 1·12, 95% CI = 1·062-1·170, P < 0·001) and IL-11 (HR = 1·37, 95% CI = 1·103-1·709, P = 0·005] were associated with worse survival. In subgroup analyses based on tumour type, colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival (HR = 2·405, 95% CI = 1·252-4·618, P = 0·008). A significant association of elevated IL-10 levels with a decrease in survival (HR = 1·824, 95% CI = 1·098-3·031, P = 0·020) was seen among patients with lung cancer. No correlation between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were associated with worse survival in cancer patients. Further, elevated IL-6 levels might be a prognostic marker in colorectal cancer and elevated IL-10 levels in lung cancer patients.

Presence of varicose veins in cancer patients increases the risk for occurrence of venous thromboembolism.

BACKGROUND: Cancer patients are at increased risk of venous thromboembolism (VTE). OBJECTIVE: We investigated the association of a history of VTE, superficial thrombophlebitis, or the presence of varicose veins with the occurrence of VTE during the course of cancer. METHODS: Cancer patients were recruited in a prospective cohort study, the Vienna Cancer and Thrombosis Study. Patients who had VTE within 3 months before study inclusion were excluded. At study inclusion, history of VTE, history of superficial thrombophlebitis, and presence of varicose veins were recorded. Primary end point was the occurrence of symptomatic VTE. Hazard ratios were obtained using the competing risk analysis according to Fine and Gray. RESULTS: The cohort consisted of 1270 patients followed over a median of 590 days. A history of VTE was found in 66 patients (5.2%), superficial thrombophlebitis in 79 patients (6.2%), and varicose veins in 160 patients (12.6%). Ninety-eight patients (7.7%) developed VTE during follow-up. The hazard ratios for the risk of VTE in patients with a history of VTE or superficial thrombophlebitis were 1.44 (95% confidence interval: 0.67-3.07) and 1.94 (1.04-3.61), respectively, and 2.01 (1.26-3.21) in those with varicose veins. In multivariable analysis including history of VTE, history of superficial thrombophlebitis, presence of varicose veins, and other patient-related factors, the presence of varicose veins (2.10 [1.29-3.41]) remained significantly associated with an increased risk of VTE. CONCLUSION: The presence of varicose veins is associated with an elevated risk of VTE in cancer patients. This clinical parameter could be useful for individual risk assessment of VTE in these patients.