Early changes of a novel APC-dependent thrombin generation assay during chemotherapy independently predict venous thromboembolism in cancer patients—a pilot study

2012 ◽  
Vol 20 (11) ◽  
pp. 2713-2720 ◽  
Author(s):  
Patrizia Ferroni ◽  
Francesca Martini ◽  
Ilaria Portarena ◽  
Italia Grenga ◽  
Silvia Riondino ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pilot Study ◽  
Cancer Patients ◽  
Thrombin Generation ◽  
Thrombin Generation Assay

An activated protein C-dependent thrombin generation assay predicts chemotherapy-associated venous thromboembolism in cancer patients

2011 ◽  
Vol 105 (05) ◽  
pp. 931-932 ◽  
Author(s):  
Francesca Martini ◽  
Ilaria Portarena ◽  
Italia Grenga ◽  
Silvia Riondino ◽  
Francesca La Farina ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Thrombin Generation Assay

Effectiveness of a multidisciplinary care program for the management of venous thromboembolism in cancer patients: a pilot study

2021 ◽  
Author(s):  
Ilham Benzidia ◽  
Benjamin Crichi ◽  
Claire Montlahuc ◽  
Hanadi Rafii ◽  
Arlette N’Dour ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pilot Study ◽  
Cancer Patients ◽  
Care Program ◽  
Multidisciplinary Care

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.

Evaluation of the procoagulant activity in the plasma of cancer patients using a thrombin generation assay

2010 ◽  
Vol 126 (6) ◽  
pp. 531-535 ◽  
Author(s):  
France Debaugnies ◽  
Marie-Agnès Azerad ◽  
Denis Noubouossié ◽  
Laurence Rozen ◽  
H. Coenraad Hemker ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Thrombin Generation ◽  
Procoagulant Activity ◽  
Thrombin Generation Assay

Comparison of the Use of TFPI Inhibition and Plasma Dilution to Increase the Sensitivity of Thrombin Generation Assay to Measure the Procoagulant Activity of Microvesicles

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4392-4392
Author(s):  
Damien DG Gheldof ◽  
François Mullier ◽  
Bernard Chatelain ◽  
jean-Michel Dogne ◽  
Christian Chatelain
Keyword(s):  
Venous Thromboembolism ◽  
Tissue Factor ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Surrogate Marker ◽  
Predictive Biomarker ◽  
Procoagulant Activity ◽  
Assay Sensitivity ◽  
Thrombin Generation Assay ◽  
Increased Risk

Abstract Abstract 4392 Introduction: Patients with cancer have a 7- to 10- fold increased risk of developing venous thromboembolism. Circulating microvesicles (MVs) could be a predictive biomarker for venous thromboembolism in cancer. Thrombin generation assay is a useful technique to detect procoagulant activity of MVs. However, thrombin generation assay suffers from a lack of sensitivity due to the presence of Tissue Factor Pathway Inhibitor (TFPI) in plasma. Aims: To improve the sensitivity of thrombin generation assay to tissue factor (TF) by limiting the interference of TFPI. Methods: Serial dilutions of MDA-MB231 cells were incubated for 45 min at 37°C to generate MVs. Samples were then centrifuged and supernatants which contain MVs were used for thrombin generation assay. Normal pooled plasma was incubated with inhibitor of TFPI or was diluted twice to decrease plasma level of TFPI. Lagtime was used as a surrogate marker of thrombin generation assay to detect procoagulant activity of MVs. Results: i) Inhibition of TFPI decreased twice the cell concentration needed for a significant reduction of lagtime and decreased 2.4-fold the intra-assay variability. ii) Plasma dilution had no impact on the thrombin generation assay sensitivity when thrombin generation assay was triggered by MVs derived from MDA-MB-231. Conclusions: Thrombin generation is a very sensitive method to study the procoagulant activity of TF-MVs. The sensitivity can be increased by inhibition of TFPI with specific monoclonal antibody against its Kunitz Domain I. A twice plasma dilution is an interesting alternative to study the procoagulant activity of MVs by thrombin generation assay with a good sensitivity, especially when low plasma quantities are available. Disclosures: No relevant conflicts of interest to declare.

PO-32 Prediction of venous thromboembolism in cancer patients by measuring thrombin generation – Results from the Vienna Cancer and Thrombosis Study (CATS)

2010 ◽  
Vol 125 ◽  
pp. S174-S175
Author(s):  
C. Ay ◽  
R. Simanek ◽  
D. Dunkler ◽  
J. Thaler ◽  
S. Koder ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Thrombin Generation

scholarly journals Exploring the utility of a novel point‐of‐care whole blood thrombin generation assay following trauma: A pilot study

2021 ◽  
Author(s):  
Michael J. Ferrara ◽  
Taleen A. MacArthur ◽  
Saulius Butenas ◽  
Kenneth G. Mann ◽  
Joseph M. Immermann ◽  
...  
Keyword(s):  
Pilot Study ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Point Of Care ◽  
Thrombin Generation Assay

scholarly journals Low Molecular Weight Heparin Modulates Thrombin Generation in Cancer Patients Undergoing Antithrombotic Therapy for Overt Venous Thromboembolism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1539-1539
Author(s):  
Anna Falanga ◽  
Carmen J Tartari ◽  
Marina R Marchetti ◽  
Laura Russo ◽  
Kim WFM Lambregts ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Procoagulant Activity ◽  
Low Molecular Weight ◽  
Cancer Associated Thrombosis ◽  
D Dimer

Abstract Introduction The incidence and recurrence rate of venous thromboembolism (VTE) are increased in the cancer compared to the non-cancer population. Low molecular weight heparin (LMWH) is recommended for both initial and long-term anticoagulant therapy for cancer-associated thrombosis, being more effective and safer than vitamin K antagonist therapy. However, failure of anticoagulation with LMWH in cancer-associated thrombosis still remains significantly elevated (VTE recurrence = 9-15%). In this study we tested whether thrombin generation (TG), a global hemostatic assay, may represent a modality to evaluate the LMWH anticoagulant level in vivo and help identifying patients at high risk for VTE recurrences. In a prospective cohort of cancer patients with VTE receiving LMWH nadroparin 200 U.I./Kg once a day, we evaluated whether LMWH treatment modulated the plasma TG capacity, together with other hemostatic parameters, i.e. microparticle (MP)-associated procoagulant activity (PCA) and D-dimer levels. Second we wished to explore whether these parameters may predict for VTE recurrence and/or bleeding. Methods Fifty eight consecutive cancer patients with acute VTE were enrolled into the study. Plasma samples were obtained at the following time intervals: at the thrombotic event (T0), at 1 month LMWH therapy (T1), and at discontinuation (T2), i.e. 6 months after VTE. Patients were followed up clinically for a total 9 months to detect overt thrombotic or bleeding events. TG was measured by the CAT assay, MP-associated procoagulant activity (PCA) by the STA Procoag PPL assay, and D-dimer by HemosIL D-dimer test. Results In this study cohort, the most represented malignancies were colon (25.9%), breast (15.5%), lung (15.5%), and gastric cancer (13.8%). Thirty six patients had metastatic disease, 22 had a limited disease. The VTE sites were: subclavian (36.2%), femoro-popliteal (20.7%), pulmonary (13.8%), jugular (8.6%), and brachial (6.9%) veins. Six patients had simultaneous femoro-popliteal venous thrombosis and pulmonary embolism. At T0 patients were characterized by a procoagulant phenotype as reflected by increased TG potential, and elevated MP-associated PCA and D-dimer compared to controls. In particular, cancer patients displayed a higher levels (p<0.01) of endogenous thrombin potential (ETP) and peak of thrombin vs controls (ETP: 1612±538 vs 1210±344 nMol*min and peak: 305±123 vs 182±84 mMol). These data were accompanied by a significant increase in MP-associated PCA (i.e. shorter clotting time 58±18 vs controls 89±12 sec; p<0.01), and D-dimer plasma levels (1430±1615 vs controls 90±96 ng/ml; p<0.01). During LMWH nadroparin therapy, a significant reduction in both TG potential (ETP-T1: 1254±810 nMol*min) and D-dimer levels (397±697 ng/ml) occurred, and after LMWH discontinuation (T2), TG potential as well as D-Dimer levels rose back, becoming similar to the control values. Differently, no reduction in MP-associated PCA was observed during LMWH therapy. Twenty-seven patients (46.6%) died during follow-up because of cancer disease. No patients had VTE recurrence. The analysis according to the stage of disease showed a significant difference with a higher mortality rate among those with a metastatic stage (p < 0.01). No correlations were observed according to chemotherapy. Conclusion Our results show that LMWH therapy modulates the global thrombin generation capacity and affects the hypercoagulable state of cancer patients, whereas MP-PCA is insensitive to it. In this cohort LMWH treatment was effective (0% VTE recurrences) and safe (1 major bleeding episode). As no recurrences were observed, it was not possible to identify a predictive value for the biological parameters. It is worth to define in a large trial the clinical utility of the TG global coagulation assay to monitor LMWH anticoagulation levels in this high risk population. Disclosures No relevant conflicts of interest to declare.

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