Platelet-derived microparticles and coagulation activation in breast cancer patients

Summary In 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 patien...

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Veröffentlicht in:Thrombosis and haemostasis 2008-10, Vol.100 (4), p.663-669
Hauptverfasser: Toth, Bettina, Liebhardt, Susanne, Steinig, Kerstin, Ditsch, Nina, Rank, Andreas, Bauerfeind, Ingo, Spannagl, Michael, Friese, Klaus, Reininger, Armin J.
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container_issue 4
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container_title Thrombosis and haemostasis
container_volume 100
creator Toth, Bettina
Liebhardt, Susanne
Steinig, Kerstin
Ditsch, Nina
Rank, Andreas
Bauerfeind, Ingo
Spannagl, Michael
Friese, Klaus
Reininger, Armin J.
description Summary In 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 = 5,637×10 6 /l; range = 2,852–8,613) and patients with distant metastases (M1; median = 6,102×10 6 /l; range = 3,350–7,445), and differed significantly from patients with insitu tumor (Tis; median = 3,220×10 6 /l; range = 2,277–4,124; p = 0.019), small tumor size (T1; median = 3,281×10 6 /l; range 2,356–4,861; p = 0.043) and women with benign breast tumor (median = 4,108×10 6 /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.
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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 = 5,637×10 6 /l; range = 2,852–8,613) and patients with distant metastases (M1; median = 6,102×10 6 /l; range = 3,350–7,445), and differed significantly from patients with insitu tumor (Tis; median = 3,220×10 6 /l; range = 2,277–4,124; p = 0.019), small tumor size (T1; median = 3,281×10 6 /l; range 2,356–4,861; p = 0.043) and women with benign breast tumor (median = 4,108×10 6 /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. 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Blood cells ; Blood Platelets - pathology ; Blood Platelets - ultrastructure ; breast cancer ; Breast Neoplasms - complications ; Case-Control Studies ; Cellular Proteolysis and Oncology ; electron microscopy ; Endothelial Cells - pathology ; Endothelial Cells - ultrastructure ; Female ; Flow Cytometry ; Fundamental and applied biological sciences. 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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 = 5,637×10 6 /l; range = 2,852–8,613) and patients with distant metastases (M1; median = 6,102×10 6 /l; range = 3,350–7,445), and differed significantly from patients with insitu tumor (Tis; median = 3,220×10 6 /l; range = 2,277–4,124; p = 0.019), small tumor size (T1; median = 3,281×10 6 /l; range 2,356–4,861; p = 0.043) and women with benign breast tumor (median = 4,108×10 6 /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. 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Psychology</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukocytes - pathology</subject><subject>Leukocytes - ultrastructure</subject><subject>Medical sciences</subject><subject>Microscopy, Electron</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Neoplasms - complications</subject><subject>Particle Size</subject><subject>Peptide Fragments - metabolism</subject><subject>Platelet diseases and coagulopathies</subject><subject>Platelet-derived microparticles</subject><subject>Prospective Studies</subject><subject>Prothrombin - metabolism</subject><subject>prothrombin fragment 1+2</subject><subject>Thrombin - metabolism</subject><subject>thrombin generation</subject><subject>Thrombosis - complications</subject><subject>Thrombosis - pathology</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNq9kc-L1TAQx4Mo7tvVm2fpRS9rNemPpDkui7rCgh6e4C1M03k2j7apmXTF_96UPlZBvInkkEz4MJ_MN4w9E_y1EJK_2d9wlQuec8mLB2xX1FLlstFfHrIdLyuey6Kqz9g50ZFzIStdP2ZnomkqUWi-Y_tPA0QcMOYdBneHXTY6G_wMITo7IGUwdZn18HVJnPNTBja6u-3opqwNCBQzC5PFkM3pHqdIT9ijAwyET0_7Bfv87u3--ia__fj-w_XVbW5lzWN6NK9kJbpGSdBC1oXSNXRWtxXXhW7SOiAiV1UJZaewVg1YwbXuWim0qKG8YC-3vnPw3xakaEZHFocBJvQLGanTvCUXCXy1gWk0ooAHMwc3QvhhBDdrimZNcS3WFBP-_NR3aUfsfsGn2BLw4gQAWRgOIc3v6J4ruOKqKKvEXW5c7B2OaI5-CVNK5G_a40aT7SFGWDDct4x98GPrKVnSj5gecPQUYa2tn-KauoFg-_SFxhEtaFShzAjTQja4OSZJUTeGev_d9HEckqz7hzKa0ToY_hAmzfQfNL_N9ROX6QUW</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>Toth, Bettina</creator><creator>Liebhardt, Susanne</creator><creator>Steinig, Kerstin</creator><creator>Ditsch, Nina</creator><creator>Rank, Andreas</creator><creator>Bauerfeind, Ingo</creator><creator>Spannagl, Michael</creator><creator>Friese, Klaus</creator><creator>Reininger, Armin J.</creator><general>Schattauer Verlag für Medizin und Naturwissenschaften</general><general>Schattauer GmbH</general><general>Schattauer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20081001</creationdate><title>Platelet-derived microparticles and coagulation activation in breast cancer patients</title><author>Toth, Bettina ; Liebhardt, Susanne ; Steinig, Kerstin ; Ditsch, Nina ; Rank, Andreas ; Bauerfeind, Ingo ; Spannagl, Michael ; Friese, Klaus ; Reininger, Armin J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c650t-1004641d876a91652795adc9b409298989feee0743a3d7e578ac1099db61915a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation - physiology</topic><topic>Blood coagulation. Blood cells</topic><topic>Blood Platelets - pathology</topic><topic>Blood Platelets - ultrastructure</topic><topic>breast cancer</topic><topic>Breast Neoplasms - complications</topic><topic>Case-Control Studies</topic><topic>Cellular Proteolysis and Oncology</topic><topic>electron microscopy</topic><topic>Endothelial Cells - pathology</topic><topic>Endothelial Cells - ultrastructure</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukocytes - pathology</topic><topic>Leukocytes - ultrastructure</topic><topic>Medical sciences</topic><topic>Microscopy, Electron</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Neoplasms - complications</topic><topic>Particle Size</topic><topic>Peptide Fragments - metabolism</topic><topic>Platelet diseases and coagulopathies</topic><topic>Platelet-derived microparticles</topic><topic>Prospective Studies</topic><topic>Prothrombin - metabolism</topic><topic>prothrombin fragment 1+2</topic><topic>Thrombin - metabolism</topic><topic>thrombin generation</topic><topic>Thrombosis - complications</topic><topic>Thrombosis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toth, Bettina</creatorcontrib><creatorcontrib>Liebhardt, Susanne</creatorcontrib><creatorcontrib>Steinig, Kerstin</creatorcontrib><creatorcontrib>Ditsch, Nina</creatorcontrib><creatorcontrib>Rank, Andreas</creatorcontrib><creatorcontrib>Bauerfeind, Ingo</creatorcontrib><creatorcontrib>Spannagl, Michael</creatorcontrib><creatorcontrib>Friese, Klaus</creatorcontrib><creatorcontrib>Reininger, Armin J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toth, Bettina</au><au>Liebhardt, Susanne</au><au>Steinig, Kerstin</au><au>Ditsch, Nina</au><au>Rank, Andreas</au><au>Bauerfeind, Ingo</au><au>Spannagl, Michael</au><au>Friese, Klaus</au><au>Reininger, Armin J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet-derived microparticles and coagulation activation in breast cancer patients</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2008-10-01</date><risdate>2008</risdate><volume>100</volume><issue>4</issue><spage>663</spage><epage>669</epage><pages>663-669</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary In 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 = 5,637×10 6 /l; range = 2,852–8,613) and patients with distant metastases (M1; median = 6,102×10 6 /l; range = 3,350–7,445), and differed significantly from patients with insitu tumor (Tis; median = 3,220×10 6 /l; range = 2,277–4,124; p = 0.019), small tumor size (T1; median = 3,281×10 6 /l; range 2,356–4,861; p = 0.043) and women with benign breast tumor (median = 4,108×10 6 /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.</abstract><cop>Stuttgart</cop><pub>Schattauer Verlag für Medizin und Naturwissenschaften</pub><pmid>18841290</pmid><doi>10.1160/TH07-10-0602</doi><tpages>7</tpages></addata></record>
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source MEDLINE; Thieme Connect Journals
subjects Adult
Aged
Aged, 80 and over
Biological and medical sciences
Blood Coagulation - physiology
Blood coagulation. Blood cells
Blood Platelets - pathology
Blood Platelets - ultrastructure
breast cancer
Breast Neoplasms - complications
Case-Control Studies
Cellular Proteolysis and Oncology
electron microscopy
Endothelial Cells - pathology
Endothelial Cells - ultrastructure
Female
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Hematologic and hematopoietic diseases
Humans
Leukocytes - pathology
Leukocytes - ultrastructure
Medical sciences
Microscopy, Electron
Middle Aged
Molecular and cellular biology
Neoplasms - complications
Particle Size
Peptide Fragments - metabolism
Platelet diseases and coagulopathies
Platelet-derived microparticles
Prospective Studies
Prothrombin - metabolism
prothrombin fragment 1+2
Thrombin - metabolism
thrombin generation
Thrombosis - complications
Thrombosis - pathology
title Platelet-derived microparticles and coagulation activation in breast cancer patients
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