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Hirudin versus heparin for use in whole blood in vitro biocompatibility models
Högskolan i Kalmar, Naturvetenskapliga institutionen.
Högskolan i Kalmar, Naturvetenskapliga institutionen. (Kristina Nilsson Ekdahl)
Högskolan i Kalmar, Naturvetenskapliga institutionen.
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2009 (Engelska)Ingår i: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 89A, nr 4, s. 951-959Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Heparin has traditionally been a widely used anticoagulant in blood research, but has been shown to be inappropriate for work with the complement system because of its complement-interacting properties. In this work, we have compared the effects of heparin with those of the specific thrombin inhibitor hirudin on complement and blood cells in vitro.

Methods: Whole blood collected in the presence of hirudin (50 µg/mL) or heparin (1 IU/mL) was incubated in the slide chamber model. The plasma was analyzed for complement activation markers C3a and sC5b-9, and the polyvinylchloride test slides were stained for adhering cells. The integrity of the complement system was tested by incubating serum and hirudin-treated plasma in the presence of various activating agents.

Results: In contrast to heparin, the addition of hirudin generally preserved the complement reactivity, and complement activation in hirudin plasma closely resembled that in normal serum. Importantly, immunochemical staining of surface-bound cells demonstrated the inducible expression of tissue factor on bound monocytes from hirudin-treated blood, an effect that was completely abolished in heparin-treated blood.

Conclusion: Our results indicate that hirudin as an anticoagulant produces more physiological conditions than heparin, making hirudin well-suited for in vitro studies, especially those addressing the regulation of cellular processes.

Ort, förlag, år, upplaga, sidor
Hoboken, NJ, US: John Wiley & Sons Inc , 2009. Vol. 89A, nr 4, s. 951-959
Nyckelord [en]
biocompatibility, complement, heparin, hirudin, whole blood models
Nationell ämneskategori
Immunologi inom det medicinska området
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:hik:diva-2786DOI: 10.1002/jbm.a.32034OAI: oai:DiVA.org:hik-2786DiVA, id: diva2:298336
Tillgänglig från: 2010-04-07 Skapad: 2010-02-22 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
Ingår i avhandling
1. Biomaterials and Hemocompatibility
Öppna denna publikation i ny flik eller fönster >>Biomaterials and Hemocompatibility
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.

This thesis includes five projects.

In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.

In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.

In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.

In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).

Ort, förlag, år, upplaga, sidor
Kalmar, Växjö: Linnaeus University Press, 2010. s. 167
Serie
Linnaeus University Dissertations ; 2/2010
Nyckelord
Complement, Coagulation, Whole blood, Biomaterials, Polymers and Hemocompatibility
Nationell ämneskategori
Immunologi inom det medicinska området
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-5437 (URN)978-91-86491-01-7 (ISBN)
Disputation
2010-01-29, N2007, Smålandsgatan 26, Kalmar, 09:30 (Engelska)
Opponent
Handledare
Tillgänglig från: 2010-04-30 Skapad: 2010-04-29 Senast uppdaterad: 2018-04-19Bibliografiskt granskad

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Bexborn, FredrikEngberg, Anna E.Sandholm, KerstinNilsson Ekdahl, Kristina

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Journal of Biomedical Materials Research. Part A
Immunologi inom det medicinska området

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