Ron Blezer
Maastricht University
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Featured researches published by Ron Blezer.
Journal of Biomedical Materials Research | 1997
Ron Blezer; Benedicte Fouache; George M. Willems; Theo Lindhout
It is hypothesized that immobilized heparin exerts a dual role in blood coagulation. On the one hand, the heparinized surface is because of its dense negative charge, thought to initiate the intrinsic pathway of blood coagulation. On the other hand, heparin is known as a potent anticoagulant drug. However, it remains to be seen how much contact-phase activation of factor XI contributes to thrombin formation and how this process is counterbalanced by which of the anti-protease activities of immobilized heparin. In the present study we examined the generation of factors XIa, IXa, and Xa, and thrombin in recalcified normal and antithrombin-depleted plasma exposed to polyacrylamide-graft polyurethane (PU) sheets modified by multipoint attachment of two different heparin species. One of them, HAH, contained the specific antithrombin binding sequence and the other one, NAH, had a low affinity for antithrombin and had no anticoagulant activity. Our data demonstrate that in contrast to PU, PU-NAH and PU-HAH are strong mediators of factor XIa and factor IXa formation in normal and antithrombin-deficient plasma. Interestingly, compared to PU-HAH and PU-NAH, thrombin formation was only slightly diminished in antithrombin-deficient plasma exposed to PU. In contrast, thrombin formation was dramatically delayed and diminished in normal plasma exposed to PU-HAH. These findings indicate that very low amounts of factor XIa apparently suffice to induce significant amounts of thrombin. In this sense, heparinized surfaces are highly thrombogenic, but our data also indicate that this activity is effectively counterbalanced by the anti-thrombin activity of the immobilized anti-coagulant species of heparin.
Biomaterials | 1997
Yvette B.J. Aldenhoff; Ron Blezer; Theo Lindhout; Leo H. Koole
Dipyridamole is a well-known vasodilator and a powerful inhibitor of activation and aggregation of blood platelets. Moreover, dipyridamole is essentially non-toxic. The drug is used extensively in clinical anti-coagulation regimes, for example pre- and post-coronary angioplasty procedures. Recently, we have found that photochemical, covalent coupling of dipyridamole to polyurethane surfaces leads to improved thromboresistance in vitro. This phenomenon is now studied in more detail. Both qualitative and more quantitative biochemical experiments were performed in order to characterize the in vitro blood compatibility of a set of polyurethane surfaces onto which dipyridamole was immobilized. First, scanning electron microscopy was used to examine the morphology of platelets which adhered during incubation with platelet-rich plasma. These experiments showed that immobilization of dipyridamole leads to a clearly decreased number of adherent platelets and to a largely diminished propensity of the surface to activate adherent platelets. Secondly, an in vitro thrombogenicity assay was run. These experiments showed that the thromboresistance increased with increasing surface density of immobilized dipyridamole. A short spacer chain separating dipyridamole from the polymer surface, was found to improve the thromboresistance further. Such a spacer chain apparently increases the efficacy of the immobilized drug. Collectively, the present results further substantiate the idea that dipyridamole retains its inhibitory activity with respect to activation and aggregation of blood platelets, when the compound is covalently attached to a polymer surface. The possible utility of these findings with respect to the development of an artificial blood vessel prosthesis is discussed briefly.
Biomaterials | 1996
Marc Anton B. Kruft; Abderazak Benzina; Ron Blezer; Leo H. Koole
Thrombosis and Haemostasis | 2000
Irene Salemink; Ron Blezer; George M. Willems; Monica Galli; Edouard M. Bevers; Theo Lindhout
Journal of Biomedical Materials Research | 1996
Abderazak Benzina; Marc-Anton B. Kruft; Ron Blezer; Theo Lindhout; Leo H. Koole; Frederik H. van der Veen; Frits W. Br
Journal of Biomedical Materials Research | 1994
Mab Marc-Anton Kruft; A Benzina; Fwhm Bär; van der Fh Frederik Veen; Cwm Cees Bastiaansen; Ron Blezer; Theo Lindhout; Leo Lh Koole
Thrombosis and Haemostasis | 1990
Theo Lindhout; Ron Blezer; H. Coenraad Hemker
Biochemical Journal | 1994
Theo Lindhout; George M. Willems; Ron Blezer; Hemker Hc
Journal of Biomedical Materials Research | 1995
Theo Lindhout; Ron Blezer; P. Schoen; George M. Willems; Benedicte Fouache; Michel Verhoeven; Marc Hendriks; Linda Cahalan; Patrick T. Cahalan
Thrombosis and Haemostasis | 1998
Ron Blezer; George M. Willems; Patrick Cahalan; Theo Lindhout