Universität zu Köln

Ruehl, Heiko, Schroeder, Lars, Mueller, Jens, Sukhitashvili, Shorena, Welz, Julia, Kuhn, Walther C., Oldenburg, Johannes, Rudlowski, Christian and Poetzsch, Bernd (2014). Impact of Hormone-Associated Resistance to Activated Protein C on the Thrombotic Potential of Oral Contraceptives: A Prospective Observational Study. PLoS One, 9 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Introduction: The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Patients and Methods: Blood samples were collected prospectively from healthy women (n = 21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. Results: All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. Conclusions: In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk.

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 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:38-431982
DOI:	10.1371/journal.pone.0105007
Journal or Publication Title:	PLoS One
Volume:	9
Number:	8
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RANDOMIZED CROSS-OVER; APC-RESISTANCE; FRAGMENT 1+2; COAGULATION; GENERATION; MUTATION; FIBRINOLYSIS; SENSITIVITY; PLASMA; BLOOD Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43198