Impact of Chemotherapy on Thrombin Generation and on the Protein C Pathway in Breast Cancer Patients

2009 ◽  
Vol 37 (2-4) ◽  
pp. 88-97 ◽  
Author(s):  
Som D. Mukherjee ◽  
Laura L. Swystun ◽  
Nigel Mackman ◽  
Jian-Guo Wang ◽  
Gregory Pond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Protein C ◽  
Thrombin Generation ◽  
Breast Cancer Patients

Platelet-derived microparticles and coagulation activation in breast cancer patients

2008 ◽  
Vol 100 (10) ◽  
pp. 663-669 ◽  
Author(s):  
Bettina Toth ◽  
Susanne Liebhardt ◽  
Kerstin Steinig ◽  
Nina Ditsch ◽  
Andreas Rank ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Patients ◽  
Tumor Size ◽  
Thrombin Generation ◽  
Annexin V ◽  
Distant Metastases ◽  
Breast Cancer Patients ◽  
Cancer Associated Thrombosis

SummaryIn the mid 1800s Trousseau observed cancer-associated thrombosis, of which the underlying pathogenesis still remains unknown. We performed a prospective study on platelet-derived microparticles (PMP) and their procoagulant potential in breast cancer patients. Fifty-eight breast cancer patients and 13 women with benign breast tumors were included in the study. Microparticles (MP) were examined by electron microscopy and FACS analysis using labels for annexinV (total numbers), CD61 (PMP), CD62P and CD63 (activated platelets), CD62E (endothelial cells), CD45 (leukocytes) as well as CD142 (tissue factor). Prothrombin fragment 1+2 (F1+2) and thrombin generation were measured as blood coagulation markers. Numbers of annexin V+-MP were highest in breast cancer patients with larger tumor size (T2; median = 5,637×106/l; range = 2,852–8,613) and patients with distant metastases (M1; median = 6,102×106/l; range = 3,350–7,445), and differed significantly from patients with insitu tumor (Tis; median = 3,220×106/l; range = 2,277–4,124; p = 0.019), small tumor size (T1; median = 3,281×106/l; range 2,356–4,861; p = 0.043) and women with benign breast tumor (median = 4,108×106/l; range = 2,530–4,874; p = 0.040). A total of 82.3% of MP were from platelets,14.6 % from endothelial cells and 0.3% from leukocytes. Less than 10% of PMP showed degranulation markers. Larger tumor size (T2) and metastases correlated with high counts of PMP and with highest F1+2 levels. Since prothrombin levels and thrombin generation did not parallel MP levels, we speculate that MP act in the microenvironment of tumor tissue and may thus not be an exclusive parameter reflecting in-vivo procoagulant activity.

scholarly journals Acquired resistance to activated protein C in breast cancer patients

2002 ◽  
Vol 120 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Marten R. Nijziel ◽  
Rene Van Oerle ◽  
M. Christella ◽  
L. G. D. Thomassen ◽  
Elisabeth C. M. Van Pampus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Protein C ◽  
Acquired Resistance ◽  
Activated Protein C ◽  
Breast Cancer Patients

scholarly journals Effect of CMF-chemotherapy on blood coagulation in patients with breast cancer

2002 ◽  
Vol 10 (2) ◽  
pp. 61-66
Author(s):  
Dragana Petrovic
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Protein C ◽  
Antithrombin Iii ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
At Iii ◽  
D Dimer

BACKGROUND: Influences of CMF (cyclophosphamide, methotrexate,5-fluorouracil) chemotherapy on blood coagulation were investigated in 30 patients receiving adjuvant chemotherapy and in 30 patients receiving chemotherapy for metastatic breast cancer. METHODS: In plasma samples of 60 patients (median age 49.5), we evaluated the following parameters 1)Markers of in vivo clotting activation thrombin-antithrombin complex (ELISA) and D-dimer (ELISA), 2) Natural anticoagulants (protein C [PC] and antithrombin III [AT III] by chromogenic methods). The coagulation studies were performed at the beginning and at the end of the first cycle of CMF protocol. RESULTS: Before CMF therapy, significant difference was observed between patients with early stage and patients with metastatic breast cancer in the PC (p<0.01), AT III (p<0.01) and TAT (p<0.01) levels. After CMF therapy, patients with stage II (adjuvant) disease manifested a significant decrease in the level of PC and AT III activity (p<0.01) and an increase in TAT level (p<0.01). In patients with disseminated breast cancer CMF therapy provoked an increased level of TAT and D-dimer with a decreased activity of protein C and antithrombin III. There was significant difference in value of TAT, D- dimer, protein C and antithrombin III between the patients with adjuvant and metastatic breast cancer patients after CMF chemotherapy CONCLUSION: Our results suggest that the application of cytotoxic therapy provokes hypercoagulable condition in breast cancer patients. This effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.

Thrombin generation predicts early recurrence in breast cancer patients

2020 ◽  
Vol 18 (9) ◽  
pp. 2220-2231 ◽  
Author(s):  
Marina Marchetti ◽  
Cinzia Giaccherini ◽  
Giovanna Masci ◽  
Cristina Verzeroli ◽  
Laura Russo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Thrombin Generation ◽  
Early Recurrence ◽  
Breast Cancer Patients

Markers of Hypercoagulability in Breast Cancer: What Is Their Clinical Relevance?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5133-5133
Author(s):  
Mourad Chaari ◽  
Grigoris T Gerotziafas ◽  
Ines Ayadi ◽  
Vassiliki Galea ◽  
Lilia Ghorbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Thrombin Generation ◽  
Cell Activation ◽  
Conflicts Of Interest ◽  
University Hospital ◽  
Activate Factor ◽  
Breast Cancer Patients ◽  
Pronounced Increase ◽  
Increased Risk

Abstract Abstract 5133 Introduction Cancer is generally combined with an increased risk of venous thromboembolism. This risk is linked to a hypercoagulable state whose precise mechanism remains unclear. It depends on the histological type, the stage of cancer and the anti-neoplasic treatment. This study aims to identify a hypercoagulability in patients with breast cancer and to define the most relevant procoagulant markers. Materials and methods A prospective study was carried out at the day hospital in the cancer department of the University Hospital H. Bourguiba in Sfax-Tunisia, from January to June 2012, including only patients with breast cancer. The thrombin generation was carried out on a venous citrated sampling (3. 2%) according to the technique of Calibrated Automated Thrombogram assay (CAT®, Diagnostica Stago, Asnières, France). The parameters of the thrombogram were analyzed: endogenous thrombin potential (ETP), peak of thrombin (peak) and mean rate index (MRI). The rates of platelet-derived microparticles expressing phosphatidyl-serine (MPP-PS+) were determined by flow cytometry using monoclonal antibodies anti-CD41 and anti-annexin V marked respectively by phycoerythrin (PE) and fluorescein isothiocyanate (FITC). D-dimers were measured by the STA-Liatest D-DI (Diagnostica-Stago) technique. The procoagulant activity of phospholipids (PPL) was measured by STA®-Procoag-PPL (Diagnostica-Stago). The plasma levels of tissue factor (TFa) were measured in a one-stage kinetic chromogenic method. This home-assay measures the ability of TF-FVIIa to activate factor X. Results Sixty one patients were included. Their mean age was 51. 8 ± 10. 9 years old. The study of the thrombogram parameters showed a significant increase of the peak of thrombin (343. 8±79. 2 nM) and of the velocity or MRI (153±56 nM/min) in patients compared to control subjects (288±48 nM, p=0. 001 and 109±33 nM/min, p<0. 001 respectively). Only 36% of patients had a significant increase of thrombin generation. D-dimers levels reached in average 1230±1760 ng/ml and 61% of patients presented relevant high values (>500 ng/ml). MPP-PS+ in cancer patients were significantly higher (9684±7865/μl) than in controls (695±361/μl, p<0. 001) but nearly 94% of patients present particularly high levels of this parameter (≥1614/μl). PPL levels were significantly higher in patients with a shorter time compared to controls (43. 4±10. 4sec versus 72 sec ± 5. 6 sec) with 97% of cancer patients below the inferior limit (60. 8sec). Besides, TFa levels were significantly increased in patients (1. 6±1. 2 pM) compared to controls (0. 22pM ± 0. 12) with 87% of cancer patients presenting particularly high values (≥0. 46pM). Conclusion Breast cancer, considered more like a tumor with a low vascular risk, is combined with a state of cell activation and hypercoagulation, almost constant, reflected by an increase of procoagulant microparticles, TF and PPL levels. Besides, thrombin generation showed a less pronounced increase in this clinical context and could contribute to discriminate patients with high or low high risk of thrombosis in breast cancer patients. This has to be confirmed by prospective studies with a clinical follow-up of cancer patients. Disclosures: No relevant conflicts of interest to declare.

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