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Thromb Haemost 2008; 100(04): 663-669
DOI: 10.1160/TH07-10-0602
Cellular Proteolysis and Oncology
Schattauer GmbH

Platelet-derived microparticles and coagulation activation in breast cancer patients

Bettina Toth
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Susanne Liebhardt
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Kerstin Steinig
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Nina Ditsch
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Andreas Rank
2   Department of Internal Medicine III – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Ingo Bauerfeind
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Michael Spannagl
3   Department of Transfusion Medicine and Haemostaseology, Clinic of Anaesthesiology, Ludwig-Maximilians-University, Munich, Germany
,
Klaus Friese
1   Department of Obstetrics and Gynecology – Großhadern, Ludwig-Maximilians-University, Munich, Germany
,
Armin J. Reininger
3   Department of Transfusion Medicine and Haemostaseology, Clinic of Anaesthesiology, Ludwig-Maximilians-University, Munich, Germany
› Author Affiliations Financial support: Bettina Toth was supported by grants of the “Friedrich Baur Stiftung”, the “Förderung für Forschung und Lehre” (FöFoLe) Program, the “Hochschul-Wissenschafts-Programm“, and the LMUexcellent Mentoring Program, all Ludwig-Maximilians-University, Munich, Germany.
Further Information

Publication History

Received 10 October 2007

Accepted after major revision 10 July 2008

Publication Date:
22 November 2017 (online)

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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 = 5,637×106/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.

Keywords

Platelet-derived microparticles - prothrombin fragment 1+2 - thrombin generation - electron microscopy - breast cancer

Footnote: This work contains part of the doctoral thesis of Kerstin Steinig and Susanne Liebhardt.


 

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