Universität zu Köln

Ruehl, Heiko, Schroeder, Lars, Mueller, Jens, Fimmers, Rolf, Sukhitashvili, Shorena, Welz, Julia, Kuhn, Walther C., Oldenburg, Johannes, Rudlowski, Christian and Poetzsch, Bernd (2014). Tamoxifen induces resistance to activated protein C. Thromb. Res., 133 (5). S. 886 - 892. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 0049-3848

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Abstract

Introduction: The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Materials and Methods: Blood samples were collected prospectively from women with breast cancer before (n= 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. Results: APC sensitivity decreased by 41% (p= 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p= 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. Conclusions: This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. (C) 2014 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ruehl, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Fimmers, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Sukhitashvili, Shorena UNSPECIFIED UNSPECIFIED UNSPECIFIED Welz, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhn, Walther C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oldenburg, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudlowski, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Poetzsch, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-439478
DOI:	10.1016/j.thromres.2014.02.004
Journal or Publication Title:	Thromb. Res.
Volume:	133
Number:	5
Page Range:	S. 886 - 892
Date:	2014
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	0049-3848
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HORMONE-THERAPY HT; ORAL-CONTRACEPTIVES; APC-RESISTANCE; VENOUS THROMBOEMBOLISM; THROMBIN GENERATION; ADJUVANT TAMOXIFEN; BREAST-CANCER; DIFFERENTIAL IMPACT; FRAGMENT 1+2; RISK Multiple languages Hematology; Peripheral Vascular Disease Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43947