The Association between Tissue Factor-Exposing Microparticles and the Activation of the Coagulation System in Cancer Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2589-2589 ◽  
Author(s):  
Ansgar Weltermann ◽  
Gregor Hron ◽  
Marietta Kollars ◽  
Gabriela Kornek ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Tissue Factor ◽  
Annexin V ◽  
Coagulation System ◽  
Related Factors ◽  
Cellular Origin ◽  
Cellular Expression ◽  
D Dimer

Abstract Background: Malignancy is a major risk factor of venous thromboembolism. In addition to circumstantial factors such as chemotherapy, the pathogenesis of thrombosis in cancer patients is directly influenced by tumor related factors. In this respect, the expression of tissue factor (TF) on tumor cells is considered to play an important role. Besides its cellular expression, more recent studies focused on TF exposure on circulating microparticles. The role of these TF exposing microparticles with regard to the pathogenesis of VTE in cancer patients, however, has not yet been investigated. We therefore conducted a prospective case control study in order to determine (a) the number and cellular origin of TF exposing microparticles in cancer patients and (b) the association between these microparticles and the activation of the coagulation system. Materials and Methods: A total of 20 patients with advanced colorectal cancer (Dukes D) and 20 healthy, age- and sex-matched controls were included. Microparticles were isolated from plasma, stained with annexin V, cell-specific antibodies and analysed by flow cytometry. The activation of the coagulation system was measured by D-dimer (ELISA). Results: Compared to the controls, the total number of TF exposing microparticles was significantly higher in the patient group (32.5 ± 23.9 vs. 18.1 ± 10.0 k/ml plasma, p = 0.007). These finding was due to a higher number of TF exposing microparticles originating from thrombocytes (12.9 ± 7.9 vs. 6.5 ± 2.9 k/ml plasma, p = 0.017) and from monocytes (9.1 ± 6.5 vs. 5.5 ± 1.4 k/ml plasma, p = 0.11) in cancer patients. Likewise, D-Dimer levels were higher among cancer patients as compared to the controls (1.61 ± 1.58 vs. 0.40 ± 0.36 μg/ml, p = 0.001). The number of TF exposing microparticles correlated with D-dimer (r = 0.67, p < 0.001). Conclusion: Both the significant elevation of TF exposing microparticles in the circulation of cancer patients and the association between these microparticles and the activation of the coagulation system suggest a potential role of TF exposing microparticles in the pathogenesis of venous thromboembolism in cancer patients.

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.

Tissue factor-positive microparticles: Cellular origin and association with coagulation activation in patients with colorectal cancer

2007 ◽  
Vol 97 (01) ◽  
pp. 119-123 ◽  
Author(s):  
Gregor Hron ◽  
Marietta Kollars ◽  
Heinz Weber ◽  
Verena Sagaster ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tissue Factor ◽  
Advanced Colorectal Cancer ◽  
Coagulation Activation ◽  
Cellular Origin ◽  
Hemostatic System ◽  
System Activation ◽  
D Dimer ◽  
Age And Sex

SummaryThe pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF+ MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF+ MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF+ MPs was two-fold higher in cancer patients: 25.9 (15.4 – 42.0) × 103 /ml plasma versus 13.1 (11.9 – 19.7) × 103 /ml plasma, p = 0.007. This was mainly due to a higher amount of TF+ MPs from platelets (13.4 [5.0 – 17.4] × 103 /ml plasma vs. 5.8 [4.5 – 7.5] × 103 /ml plasma, p = 0.017). TF+ MPs correlated with D-dimer (ρ = 0.48, p = 0.002). High levels of TF+ MPs in cancer patients and their correlation with D-dimer suggest that TF+ MPs might be involved in hemostasis activation in cancer patients.

D-dimers: a most misunderstood test

2021 ◽  
Vol 82 (8) ◽  
pp. 1-5
Author(s):  
Luke Carter-Brzezinski ◽  
Scott Houston ◽  
Jecko Thachil
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Settings ◽  
Treatment Pathways ◽  
D Dimer

The role of D-dimers in the management of venous thromboembolism is well established and testing for D-dimers has become common in most acute settings. Although it has been validated for the purpose of excluding venous thromboembolism, the test is increasingly ordered to ‘diagnose’ venous thromboembolism. Furthermore, in the COVID-19 pandemic, heavy reliance has been put on this test with the inclusion of D-dimers to guide treatment pathways. This review summarises the appropriateness of D-dimer tests in these different clinical settings.

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

Significant Correlations between Tissue Factor and Thrombin Markers in Trauma and Septic Patients with Disseminated Intravascular Coagulation

1998 ◽  
Vol 79 (06) ◽  
pp. 1111-1115 ◽  
Author(s):  
Satoshi Nanzaki ◽  
Shigeyuki Sasaki ◽  
Osamu Kemmotsu ◽  
Satoshi Gando
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Thrombin Generation ◽  
Trauma Patients ◽  
Elevated Plasma ◽  
Antigen Concentration ◽  
Intravascular Coagulation ◽  
Factor Antigen ◽  
D Dimer

SummaryTo determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 ± 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

scholarly journals Should We Replace the Terms Intrinsic and Extrinsic Coagulation Pathways With Tissue Factor Pathway?

2016 ◽  
Vol 23 (8) ◽  
pp. 922-927 ◽  
Author(s):  
Jan F. Vojacek
Keyword(s):  
Tissue Factor ◽  
Coagulation Cascade ◽  
Coagulation System ◽  
Bleeding Complications ◽  
Antithrombotic Agents ◽  
Risk Of Bleeding ◽  
Tissue Factor Pathway ◽  
The Common ◽  
Coagulation Pathway

Present review highlights some new aspects of the role of individual components of blood coagulation process and proposes a modified concept of hemocoagulation cascade. The role of FXII in the initiation of the so-called intrinsic coagulation system is currently questioned. Its role has been recently demonstrated mainly in the thrombus propagation and final stabilization together with factors XI and XIII. The edited concept underlines the common part of the tissue factor (TF) in the initiation of both the intrinsic and extrinsic pathways of the coagulation system and therefore may make it not improperly be called the TF coagulation pathway. The search for new antithrombotic agents shows that the level of the coagulation system blockade depends on which step in the coagulation cascade is targeted and results in different degrees of the antithrombotic efficiency and the risk of bleeding complications.

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