Integrin genetic variants and risk of thromboembolic events in patients with colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 462-462
Author(s):  
Gerald Prager ◽  
Alexandra Schuler ◽  
Cihan Ay ◽  
Clemens Pausz ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Tumor Biology ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Direct Dna Sequencing ◽  
Increased Risk ◽  
Colorectal Cancer Patients ◽  
Integrin Beta 3

462 Background: Patients with colorectal cancer are at increased risk of venous thromboembolism (VTE). Integrin beta-3 are involved in tumor biology as well as platelet aggregation, thus, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in the integrin beta-3 gene could predict the risk of VTE in colorectal cancer patients. Methods: The study population comprises patients recruited into the Vienna Cancer and Thrombosis Study (CATS) (Ay, C et al; JCO 2011 vol. 29 no. 15), an ongoing prospective observational cohort study initiated in October 2003 at the Medical University of Vienna. In 114 out of 139 patients diagnosed with colon cancer DNA was assessable for integrin beta-3 germline SNPs rs3809865, rs5918, rs4642 characterization. Whole blood samples were analyzed using PCR-RFLP or direct DNA-sequencing. VTE events were statistical analyzed using one-way Anova testing. Results: The patient’s demographics and tumor characteristics were balanced between groups. VTE occurred in 14 patients (12.28%). In colorectal cancer patients with an rs3809865 A/A allele profile a statistical significant (p=0.0015) increased risk of VTE events was observed as 12 (25%) of 48 patients experienced VTE. Only 2 of 52 patients (3.85%) harboring an A/T allele VTE was diagnosed. None (0%) of the T/T subgroup had any VTE. Other SNPs revealed no predictive value for VTE. In multivariable analysis including age, sex, chemotherapy, and anti-VEGF therapy rs3809865 A/A allele profile remained a statistical significant risk factor for VTE. Conclusions: This study identifies germline polymorphisms in integrin genes as independent prognostic markers for VTE in colorectal cancer. These data may help to select subgroups of patients who may benefit from an enforced prophylaxis of venous thromboembolism (VTE).

scholarly journals Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients

2015 ◽  
Vol 136 (5) ◽  
pp. 865-869 ◽  
Author(s):  
Daniela Bianconi ◽  
Alexandra Schuler ◽  
Clemens Pausz ◽  
Angelika Geroldinger ◽  
Alexandra Kaider ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Genetic Variants ◽  
Colorectal Cancer Patients ◽  
Integrin Beta 3

High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2703-2708 ◽  
Author(s):  
Cihan Ay ◽  
Ralph Simanek ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Guelay Alguel ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cumulative Probability ◽  
Increased Risk ◽  
Soluble P

Abstract Cancer patients are at high risk for venous thromboembolism (VTE). Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups. The cell adhesion molecule P-selectin was recently identified as risk factor for VTE. To investigate soluble P-selectin (sP-selectin) in cancer patients as risk predictor for VTE, we performed a prospective cohort study of 687 cancer patients and followed them for a median (IQR) of 415 (221-722) days. Main tumor entities were malignancies of the breast (n = 125), lung (n = 86), gastrointestinal tract (n = 130), pancreas (n = 42), kidney (n = 19), prostate (n = 72), and brain (n = 80); 91 had hematologic malignancies; 42 had other tumors. VTE occurred in 44 (6.4%) patients. In multivariable analysis, elevated sP-selectin (cutoff level, 53.1 ng/mL, 75th percentile of study population) was a statistically significant risk factor for VTE after adjustment for age, sex, surgery, chemotherapy, and radiotherapy (hazard ratio = 2.6, 95% confidence interval, 1.4-4.9, P = .003). The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin above and 3.7% in those below the 75th percentile (P = .002). High sP-selectin plasma levels independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE.

scholarly journals VEGF Inhibitors Do Not Increase D-dimer Levels in Colorectal Cancer Patients Without Venous Thromboembolism : A Retrospective Non-inferiority Analysis

In Vivo ◽  
2019 ◽  
Vol 33 (6) ◽  
pp. 2117-2123
Author(s):  
HIROKAZU TOSHIMA ◽  
TOSHIKAZU IKUSUE ◽  
ATSUSHI HISAMATSU ◽  
KOUJI KOBAYASHI ◽  
HIROO ISHIDA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vegf Inhibitors ◽  
Colorectal Cancer Patients ◽  
D Dimer

Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3824-3824
Author(s):  
Cihan Ay ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Ralph Simanek ◽  
Alexandru-Laurentiu Chiriac ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Predictive Value ◽  
Significant Risk ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Diagnosis Of Cancer ◽  
D Dimer

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.

Effects of Chemotherapy on Extracellular Vesicles and Coagulation Activation in Colorectal Cancer Patients: A Pilot Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1425-1425
Author(s):  
Ludwig Traby ◽  
Hannah C. Puhr ◽  
Marietta Kollars ◽  
Kammer Michael ◽  
Gerald Prager ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Pilot Study ◽  
Cancer Patients ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Advanced Colorectal Cancer ◽  
Coagulation Activation ◽  
Colorectal Cancer Patients ◽  
D Dimer

Abstract Introduction Venous thromboembolism is a frequent complication in cancer patients and results in a considerable morbidity and mortality. The underlying mechanisms leading to the increased thrombotic risk are yet poorly understood. We have previously shown that levels of extracellular vesicles (EV) are elevated in patients with colorectal cancer compared to healthy control individuals (Hron et al, Thromb Haemost 2007;97:119-123). EV originate from blood or endothelial cells, or from the underlying tumor itself. They may contribute to coagulation activation and propagation by exposing tissue factor and by providing a surface for the interaction of coagulation factors. In that study, the number of EV was also positively correlated with levels of D-dimer, a fibrin split product and marker of coagulation activation. We hypothesize that number of EV and levels of D-dimer decline with decreasing tumor load during antineoplastic treatment. Therefore, the study aims at evaluating the long-term effect of chemotherapy on hemostatic system activation in patients with advanced colorectal cancer. Methods We conducted a pilot study including patients receiving chemotherapy because of advanced colorectal cancer. All chemotherapy regimens were based on 5-fluorouracilcombined with either oxaliplatin or irinotecan without or with an antibody (bevacizumab in 72%, cetuximab in 11%, and ramucirumab in 5% of patients, respectively). Patients were followed for 3 chemotherapy cycles. The study was approved by the local ethics committee, was conducted according to the Declaration of Helsinki and informed consent was obtained from all study patients. Venous blood was sampled at each cycle immediately before chemotherapy and was centrifuged at 2600 g for 15 minutes. The number of EV was assessed by flow cytometry using a FACSCalibur® flow cytometer with CellQuest™ software (Becton Dickinson) immediately after blood collection and centrifugation in fresh plasma. EV were defined by size (forward scatter, <1 µm) and annexin V binding. Tissue factor positive EV were characterized by an anti-CD142 antibody. Plasma was then frozen and stored at -80°C and was used for determination of markers of coagulation activation (D-dimer, prothrombin fragment f1.2) by commercially available ELISA kits. All outcome variables were log-transformed due to skewed distributions. The paired t-test was used to compare baseline (before the 1st chemotherapy) levels with measurements obtained from the 2nd and 3rd blood sampling. In order to provide a clearer legibility, all data is presented in absolute numbers and all values are given as median (quartiles) if not otherwise stated. Results 18 patients completed 3 cycles of chemotherapy. Their mean (± SD) age was 60.5 (± 12.2) years and 14 (78%) were men. None of the patients developed venous thromboembolism. Table 1 shows the levels of coagulation activation markers and the number of EV at baseline and before the 2nd and 3rd cycle of chemotherapy, respectively. D-dimer levels were 1.22 (0.42-2.31) µg mL-1 at baseline and significantly decreased over the course of treatment. D-dimer levels did not correlate with the number of EV either at baseline or at later time points. The number of EV decreased from 474 (312-617) x 103 mL-1 at baseline to 359 (239-474) x 103 mL-1 before the 3rd cycle. The proportion of tissue factor positive EV was small at baseline and throughout treatment. Levels of prothrombin fragment f1.2 did not change during treatment and did not correlate with number of EV at any time point. Conclusions In patients with advanced colorectal cancer chemotherapy attenuates coagulation activation as indicated by a decline of D-dimer levels and number of EV. These findings warrant further studies in a larger patient population and longer observation time. Table 1 Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Table 1. Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Disclosures No relevant conflicts of interest to declare.

scholarly journals Genes associated with venous thromboembolism in colorectal cancer patients

2018 ◽  
Vol 16 (2) ◽  
pp. 293-302 ◽  
Author(s):  
B. Ünlü ◽  
N. van Es ◽  
W. Arindrarto ◽  
S. M. Kiełbasa ◽  
H. Mei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Colorectal Cancer Patients

scholarly journals Influence of Tumor Thrombus on Occurrence of Distant Venous Thromboembolism and Survival in Patients With Renal Cell Carcinoma After Surgery

2019 ◽  
Vol 25 ◽  
pp. 107602961882328 ◽  
Author(s):  
Hyunkyung Park ◽  
Chang Wook Jeong ◽  
Hyeongdong Yuk ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Venous Thromboembolism ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Thrombus ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Increased Risk ◽  
The Impact

Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.

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