title: Hemocompatibility testing according to ISO 10993-4: discrimination between pyrogen- and device-induced hemostatic activation.
abstract: Next to good hemocompatibility performance of new medical devices, which has to be tested according to the ISO 10993-4, the detection of pyrogen-contaminated devices plays a pivotal role for safe device application. During blood contact with pyrogen-contaminated devices, intense inflammatory and hemostatic reactions are feared. The aim of our study was to investigate the influence of pyrogenic contaminations on stents according to the ISO 10993-4. The pyrogens of different origins like lipopolysaccharides (LPS), purified lipoteichoic acid (LTA) or zymosan were used. These pyrogens were dried on stents or dissolved and circulated in a Chandler-loop model for 90 min at 37°C with human blood. Before and after circulation, parameters of the hemostatic system including coagulation, platelets, complement and leukocyte activation were investigated. The complement system was activated by LPS isolated from Klebsiella pneumoniae and Pseudomonas aeruginosa and by LTA. Leukocyte activation was triggered by LPS isolated from K. pneumoniae, LTA and zymosan, whereas coagulation and platelet activation were only slightly influenced. Our data indicate that pyrogen-contaminated devices lead to an alteration in the hemostatic response when compared to depyrogenized devices. Therefore, pyrogenicity testing should be performed prior to hemocompatibility tests according to ISO 10993-4 in order to exclude hemostatic activation induced by pyrogen contaminations.
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: katharina.stang@googlemail.com.
authors: Katharina
authors: K
authors: Stang
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: stefanie.krajewski@uni-tuebingen.de.
authors: Stefanie
authors: S
authors: Krajewski
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: b.neumann.71@web.de.
authors: Bernd
authors: B
authors: Neumann
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: kurzjulia@gmx.de.
authors: Julia
authors: J
authors: Kurz
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: marcell.post@gmx.de.
authors: Marcell
authors: M
authors: Post
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: Sandra.stoppelkamp@uni-tuebingen.de.
authors: Sandra
authors: S
authors: Stoppelkamp
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: stefan.fennrich@klinikum.uni-tuebingen.de.
authors: Stefan
authors: S
authors: Fennrich
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: meltem.avci-adali@uni-tuebingen.de.
authors: Meltem
authors: M
authors: Avci-Adali
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany.
authors: Doris
authors: D
authors: Armbruster
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: Christian.schlensak@med-uni-tuebingen.de.
authors: Christian
authors: C
authors: Schlensak
authors: Department of Small Animal Medicine, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 23, 04109 Leipzig, Germany. Electronic address: burgener@kleintierklinik.uni-leipzig.de.
authors: Iwan Anton
authors: IA
authors: Burgener
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: hans-peter.wendel@med.uni-tuebingen.de.
authors: Hans Peter
authors: HP
authors: Wendel
authors: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany. Electronic address: Tobias.Walker@med-uni-tuebingen.de.
authors: Tobias
authors: T
authors: Walker
mesh_terms: D001419:Bacteria / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity; D001790:Blood Physiological Phenomena / Q000187:drug effects*; D004869:Equipment Safety; D006461:Hemolysis / Q000187:drug effects; D006487:Hemostasis; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity; D008422:Materials Testing / Q000379:methods / Q000592:standards; D011749:Pyrogens / Q000737:chemistry / Q000633:toxicity
chemical_list: D001672:Biocompatible Materials; D008070:Lipopolysaccharides; D011749:Pyrogens
keywords: Hemocompatibility; ISO 10993-4; Medical devices; Pyrogens; Surface contamination