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1. First world consensus conference on pancreas transplantation: Part I-Methods and results of literature search

Author

Boggi, U., Vistoli, F., Marchetti, P., Kandaswamy, R., Berney, T., Andres, A., Arbogast, H. P., Badet, L., Baronti, W., Bartlett, S. T., Benedetti, E., Branchereau, J., Burke, G. W. 3., Buron, F., Caldara, R., Cardillo, M., Casanova, D., Cipriani, F., Cooper, M., Cupisti, A., de Koning, E. J. P., Davide, J., Drachenberg, C., Ettorre, G. M., Fernandez Cruz, L., Fridell, J. A., Friend, P. J., Furian, L., Gaber, O. A., Gruessner, A. C., Gruessner, R. W. G., Gunton, J. E., Han, D. -J., Iacopi, S., Kauffmann, E. F., Kaufman, D., Kenmochi, T., Khambalia, H. A., Lai, Q., Langer, R. M., Maffi, P., Marselli, L., Menichetti, F., Miccoli, M., Mittal, S., Morelon, E., Napoli, N., Neri, F., Oberholzer, J., Odorico, J. S., Ollinger, R., Oniscu, G., Orlando, G., Ortenzi, M., Perosa, M., Perrone, V. G., Redfield, R. R., Ricci, C., Rigotti, P., Robertson, R. P., Ross, L. F., Rossi, M., Saudek, F., Scalea, J. R., Schenker, P., Secchi, A., Socci, C., Sousa Silva, D., Squifflet, J. P., Stock, P. G., Stratta, R. J., Terrenzio, C., Uva, P., Watson, C. C. E., White, S. A., Boggi U., Vistoli F., Marchetti P., Kandaswamy R., Berney T., Andres A., Arbogast H.P., Badet L., Baronti W., Bartlett S.T., Benedetti E., Branchereau J., Burke G.W., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., de Koning E.J.P., Davide J., Drachenberg C., Ettorre G.M., Fernandez Cruz L., Fridell J.A., Friend P.J., Furian L., Gaber O.A., Gruessner A.C., Gruessner R.W.G., Gunton J.E., Han D.-J., Iacopi S., Kauffmann E.F., Kaufman D., Kenmochi T., Khambalia H.A., Lai Q., Langer R.M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J.S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V.G., Redfield R.R., Ricci C., Rigotti P., Robertson R.P., Ross L.F., Rossi M., Saudek F., Scalea J.R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J.P., Stock P.G., Stratta R.J., Terrenzio C., Uva P., Watson C.C.E., and White S.A.

Subjects
clinical research / practice, diabetes, pancreas / simultaneous pancreas-kidney transplantation, survey, Consensus, Humans, Pancreas Transplantation, medicine.medical_treatment, media_common.quotation_subject, Delphi method, Consensu, Pancreas transplantation, Session (web analytics), Jury, Voting, medicine, Immunology and Allergy, Pharmacology (medical), Grading (education), media_common, Transplantation, Medical education, business.industry, pancreas / simultaneous pancreas‐kidney transplantation, Systematic review, diabete, Special Articles, Original Article, First World, business, Human
Abstract

Comprehensive evidence‐based guidelines for the practice of pancreas transplantation are yet to be established. The First World Consensus Conference on Pancreas Transplantation was convened for this purpose. A steering committee selected the participants and defined the questions to be addressed. A group of literature reviewers identified 597 studies to be included in summaries for guidelines production. Expert groups formulated the first draft of recommendations. Two rounds of discussion and voting occurred online, using the Delphi method (agreement rate ≥85%). After each round, critical responses of experts were reviewed, and recommendations were amended accordingly. Recommendations were finalized after live discussions. Each session was preceded by expert presentations and a summary of results of systematic literature review. Up to three voting rounds were allowed for each recommendation. To avoid potential conflicts of interest, deliberations on issues regarding the impact of pancreas transplantation on the management of diabetes were conducted by an independent jury. Recommendations on technical issues were determined by experts and validated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Quality of evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. Each recommendation received a GRADE rating (Grading of Recommendations, Assessment, Development and Evaluations)., This article presents the results of literature search and the methods used to provide evidence‐based guidelines for the practice of pancreas transplantation at the First World Consensus Conference on Pancreas Transplantation.

Published
2021

3. First world consensus conference on pancreas transplantation: Part I—Methods and results of literature search

Author

Boggi, U, Vistoli, F, Marchetti, P, Kandaswamy, R, Berney, T, Andres, A, Arbogast, H, Badet, L, Baronti, W, Bartlett, S, Benedetti, E, Branchereau, J, Burke, G, Buron, F, Caldara, R, Cardillo, M, Casanova, D, Cipriani, F, Cooper, M, Cupisti, A, de Koning, E, Davide, J, Drachenberg, C, Ettorre, G, Fernandez Cruz, L, Fridell, J, Friend, P, Furian, L, Gaber, O, Gruessner, A, Gruessner, R, Gunton, J, Han, D, Iacopi, S, Kauffmann, E, Kaufman, D, Kenmochi, T, Khambalia, H, Lai, Q, Langer, R, Maffi, P, Marselli, L, Menichetti, F, Miccoli, M, Mittal, S, Morelon, E, Napoli, N, Neri, F, Oberholzer, J, Odorico, J, Ollinger, R, Oniscu, G, Orlando, G, Ortenzi, M, Perosa, M, Perrone, V, Redfield, R, Ricci, C, Rigotti, P, Robertson, R, Ross, L, Rossi, M, Saudek, F, Scalea, J, Schenker, P, Secchi, A, Socci, C, Sousa Silva, D, Squifflet, J, Stock, P, Stratta, R, Terrenzio, C, Uva, P, Watson, C, White, S, Boggi U., Vistoli F., Marchetti P., Kandaswamy R., Berney T., Andres A., Arbogast H. P., Badet L., Baronti W., Bartlett S. T., Benedetti E., Branchereau J., Burke G. W. 3., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., de Koning E. J. P., Davide J., Drachenberg C., Ettorre G. M., Fernandez Cruz L., Fridell J. A., Friend P. J., Furian L., Gaber O. A., Gruessner A. C., Gruessner R. W. G., Gunton J. E., Han D. -J., Iacopi S., Kauffmann E. F., Kaufman D., Kenmochi T., Khambalia H. A., Lai Q., Langer R. M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J. S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V. G., Redfield R. R., Ricci C., Rigotti P., Robertson R. P., Ross L. F., Rossi M., Saudek F., Scalea J. R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J. P., Stock P. G., Stratta R. J., Terrenzio C., Uva P., Watson C. C. E., White S. A., Boggi, U, Vistoli, F, Marchetti, P, Kandaswamy, R, Berney, T, Andres, A, Arbogast, H, Badet, L, Baronti, W, Bartlett, S, Benedetti, E, Branchereau, J, Burke, G, Buron, F, Caldara, R, Cardillo, M, Casanova, D, Cipriani, F, Cooper, M, Cupisti, A, de Koning, E, Davide, J, Drachenberg, C, Ettorre, G, Fernandez Cruz, L, Fridell, J, Friend, P, Furian, L, Gaber, O, Gruessner, A, Gruessner, R, Gunton, J, Han, D, Iacopi, S, Kauffmann, E, Kaufman, D, Kenmochi, T, Khambalia, H, Lai, Q, Langer, R, Maffi, P, Marselli, L, Menichetti, F, Miccoli, M, Mittal, S, Morelon, E, Napoli, N, Neri, F, Oberholzer, J, Odorico, J, Ollinger, R, Oniscu, G, Orlando, G, Ortenzi, M, Perosa, M, Perrone, V, Redfield, R, Ricci, C, Rigotti, P, Robertson, R, Ross, L, Rossi, M, Saudek, F, Scalea, J, Schenker, P, Secchi, A, Socci, C, Sousa Silva, D, Squifflet, J, Stock, P, Stratta, R, Terrenzio, C, Uva, P, Watson, C, White, S, Boggi U., Vistoli F., Marchetti P., Kandaswamy R., Berney T., Andres A., Arbogast H. P., Badet L., Baronti W., Bartlett S. T., Benedetti E., Branchereau J., Burke G. W. 3., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., de Koning E. J. P., Davide J., Drachenberg C., Ettorre G. M., Fernandez Cruz L., Fridell J. A., Friend P. J., Furian L., Gaber O. A., Gruessner A. C., Gruessner R. W. G., Gunton J. E., Han D. -J., Iacopi S., Kauffmann E. F., Kaufman D., Kenmochi T., Khambalia H. A., Lai Q., Langer R. M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J. S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V. G., Redfield R. R., Ricci C., Rigotti P., Robertson R. P., Ross L. F., Rossi M., Saudek F., Scalea J. R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J. P., Stock P. G., Stratta R. J., Terrenzio C., Uva P., Watson C. C. E., and White S. A.

Abstract

Comprehensive evidence-based guidelines for the practice of pancreas transplantation are yet to be established. The First World Consensus Conference on Pancreas Transplantation was convened for this purpose. A steering committee selected the participants and defined the questions to be addressed. A group of literature reviewers identified 597 studies to be included in summaries for guidelines production. Expert groups formulated the first draft of recommendations. Two rounds of discussion and voting occurred online, using the Delphi method (agreement rate ≥85%). After each round, critical responses of experts were reviewed, and recommendations were amended accordingly. Recommendations were finalized after live discussions. Each session was preceded by expert presentations and a summary of results of systematic literature review. Up to three voting rounds were allowed for each recommendation. To avoid potential conflicts of interest, deliberations on issues regarding the impact of pancreas transplantation on the management of diabetes were conducted by an independent jury. Recommendations on technical issues were determined by experts and validated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Quality of evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. Each recommendation received a GRADE rating (Grading of Recommendations, Assessment, Development and Evaluations).

Published
2021

4. First World Consensus Conference on pancreas transplantation: Part II – recommendations

Author

Boggi, U, Vistoli, F, Andres, A, Arbogast, H, Badet, L, Baronti, W, Bartlett, S, Benedetti, E, Branchereau, J, Burke, G, Buron, F, Caldara, R, Cardillo, M, Casanova, D, Cipriani, F, Cooper, M, Cupisti, A, Davide, J, Drachenberg, C, de Koning, E, Ettorre, G, Fernandez Cruz, L, Fridell, J, Friend, P, Furian, L, Gaber, O, Gruessner, A, Gruessner, R, Gunton, J, Han, D, Iacopi, S, Kauffmann, E, Kaufman, D, Kenmochi, T, Khambalia, H, Lai, Q, Langer, R, Maffi, P, Marselli, L, Menichetti, F, Miccoli, M, Mittal, S, Morelon, E, Napoli, N, Neri, F, Oberholzer, J, Odorico, J, Ollinger, R, Oniscu, G, Orlando, G, Ortenzi, M, Perosa, M, Perrone, V, Pleass, H, Redfield, R, Ricci, C, Rigotti, P, Paul Robertson, R, Ross, L, Rossi, M, Saudek, F, Scalea, J, Schenker, P, Secchi, A, Socci, C, Sousa Silva, D, Squifflet, J, Stock, P, Stratta, R, Terrenzio, C, Uva, P, Watson, C, White, S, Marchetti, P, Kandaswamy, R, Berney, T, Boggi U., Vistoli F., Andres A., Arbogast H. P., Badet L., Baronti W., Bartlett S. T., Benedetti E., Branchereau J., Burke G. W., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., Davide J., Drachenberg C., de Koning E. J. P., Ettorre G. M., Fernandez Cruz L., Fridell J. A., Friend P. J., Furian L., Gaber O. A., Gruessner A. C., Gruessner R. W. G., Gunton J. E., Han D. -J., Iacopi S., Kauffmann E. F., Kaufman D., Kenmochi T., Khambalia H. A., Lai Q., Langer R. M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J. S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V. G., Pleass H., Redfield R. R., Ricci C., Rigotti P., Paul Robertson R., Ross L. F., Rossi M., Saudek F., Scalea J. R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J. P., Stock P. G., Stratta R. J., Terrenzio C., Uva P., Watson C. C. E., White S. A., Marchetti P., Kandaswamy R., Berney T., Boggi, U, Vistoli, F, Andres, A, Arbogast, H, Badet, L, Baronti, W, Bartlett, S, Benedetti, E, Branchereau, J, Burke, G, Buron, F, Caldara, R, Cardillo, M, Casanova, D, Cipriani, F, Cooper, M, Cupisti, A, Davide, J, Drachenberg, C, de Koning, E, Ettorre, G, Fernandez Cruz, L, Fridell, J, Friend, P, Furian, L, Gaber, O, Gruessner, A, Gruessner, R, Gunton, J, Han, D, Iacopi, S, Kauffmann, E, Kaufman, D, Kenmochi, T, Khambalia, H, Lai, Q, Langer, R, Maffi, P, Marselli, L, Menichetti, F, Miccoli, M, Mittal, S, Morelon, E, Napoli, N, Neri, F, Oberholzer, J, Odorico, J, Ollinger, R, Oniscu, G, Orlando, G, Ortenzi, M, Perosa, M, Perrone, V, Pleass, H, Redfield, R, Ricci, C, Rigotti, P, Paul Robertson, R, Ross, L, Rossi, M, Saudek, F, Scalea, J, Schenker, P, Secchi, A, Socci, C, Sousa Silva, D, Squifflet, J, Stock, P, Stratta, R, Terrenzio, C, Uva, P, Watson, C, White, S, Marchetti, P, Kandaswamy, R, Berney, T, Boggi U., Vistoli F., Andres A., Arbogast H. P., Badet L., Baronti W., Bartlett S. T., Benedetti E., Branchereau J., Burke G. W., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., Davide J., Drachenberg C., de Koning E. J. P., Ettorre G. M., Fernandez Cruz L., Fridell J. A., Friend P. J., Furian L., Gaber O. A., Gruessner A. C., Gruessner R. W. G., Gunton J. E., Han D. -J., Iacopi S., Kauffmann E. F., Kaufman D., Kenmochi T., Khambalia H. A., Lai Q., Langer R. M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J. S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V. G., Pleass H., Redfield R. R., Ricci C., Rigotti P., Paul Robertson R., Ross L. F., Rossi M., Saudek F., Scalea J. R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J. P., Stock P. G., Stratta R. J., Terrenzio C., Uva P., Watson C. C. E., White S. A., Marchetti P., Kandaswamy R., and Berney T.

Abstract

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Published
2021

5. The Concept of Interactive Business Competence in English and German.

Author

Gerzymisch-Arbogast, H.

Abstract

The status of different approaches to teaching business English in West Germany are explored, and it is concluded that business profiles, business situations, and the development of language skills must be considered in designing a business language course. The concept of interactive business competence in English and German as a basis for business language instruction is based on the understanding that language is a form of interaction transcending language skills, and that interactive language teaching needs to incorporate intercultural aspects into a situational approach. The perspective taken is that of a designer of business English instruction in Germany. It is concluded that: (1) business language courses should be oriented to the roles students will assume later in their jobs, (2) teaching methods should use a business-related situational approach emphasizing formal and informal communication, and (3) the overall goals of the programs should be to prepare students to interact competently in English in their roles as managers. (MSE)

Published
1988

14. Prospective Age-Matching in Elderly Kidney Transplant Recipients-A 5-Year Analysis of the Eurotransplant Senior Program

Author

Frei, U., Noeldeke, J., Machold-Fabrizii, V., Arbogast, H., Margreiter, R., Fricke, L., Voiculescu, A., Kliem, V., Ebel, H., Albert, U., Lopau, K., Schnuelle, P., Nonnast-Daniel, B., Pietruck, F., Offermann, R., Persijn, G., and Bernasconi, C.

Abstract

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged ?65 years to recipients ?65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any OA, donor age ?65, n 446) or recipient age (any to old, AO, recipient age 60-64, n 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7 vs. OA 36.2, p 0.047) but 5-10 higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Published
2008
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19. Calcineurin inhibitor-free immunosuppressive strategy in elderly recipients of renal allografts from deceased donors: 1-year results from a prospective single center trial.

Author

Arbogast HP, Hoffmann JN, Illner WD, Hillebrand GF, Fischereder M, Jauch KW, and Land W

Subjects
Aged, Aged, 80 and over, Animals, Antibodies, Monoclonal therapeutic use, Antilymphocyte Serum therapeutic use, Basiliximab, Cadaver, Calcineurin immunology, Calcineurin Inhibitors, Graft Rejection epidemiology, Graft Rejection prevention & control, Humans, Kidney Function Tests, Kidney Transplantation mortality, Mycophenolic Acid therapeutic use, Prospective Studies, Rabbits, Recombinant Fusion Proteins therapeutic use, Survival Rate, Time Factors, Tissue Donors, Immunosuppressive Agents therapeutic use, Kidney Transplantation immunology, Mycophenolic Acid analogs & derivatives
Abstract

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.

Published
2009
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20. [Antithrombogenicity of human endothelial cells].

Author

Arbogast HP

Subjects
Endothelium, Vascular embryology, Endothelium, Vascular growth & development, Humans, Microcirculation physiology, Thrombin physiology, Umbilical Veins physiology, Antithrombins biosynthesis, Endothelium, Vascular physiology
Abstract

Unlabelled: In the preceeding decades, our understanding of the complexity in our haemostaseologic system has been evolutionized from a purely ex vivo standpoint to an increasingly in vivo oriented approach, by more and more respecting the immense metabolic interactions of our vascular endothelium, mainly thrombin, the central serine protease in our coagulatory system. So far, investigations concerning human endothelium only relied on experiments with embryonic human endothelial cells, derived from umbilical cord veins. The underlying investigation confronts the justified question about the transferability of such embryonic results to the adult vascular system., Material, Methods: Micro- and macrovascular endothelial cells were isolated, purified and propagated in pure cultures. Integrated into an established filtration model, their potential to mediate antithrombogenicity was investigated., Results, Conclusion: Surprisingly, immense differences in thrombin-induced antithrombogenicity were demonstrated. This justifies doubts concerning the transferability of HUVEC-based results to the whole human vascular system.

Published
2005

21. [Thrombin: antithrombotic properties and pharmacological consequences].

Author

Arbogast HP

Subjects
Antithrombins pharmacokinetics, Antithrombins pharmacology, Blood Coagulation Factors physiology, Endothelium, Vascular drug effects, Endothelium, Vascular physiology, Fibrin physiology, Humans, Models, Biological, Thrombosis prevention & control, Antithrombins therapeutic use, Thrombin physiology
Abstract

During the last few years, the availability of endothelial cell cultures isolated from different vascular regions contributed to a significant increase in understanding the complex pro- and antithrombotic mechanisms in our circulatory system. The most important key enzyme is thrombin. Due to its haemostatic properties this serin protease catalyzes fibrin formation, activation of factors V, VIII and XIII as well as irreversible platelet aggregation. These processes may occur even within the circulatory system in case of endothelial stimulation (e. g. by inflammation mediators) for expression of binding sites for factors IX, IXa, X, Xa, von Willebrand protein and PAF. Thus not only catalytically activated coagulatory cascades, but also enhanced cooperation of platelets and granulocytes will occur. Paradoxically, in low intravascular concentration, thrombin, in combination with a healthy endothelial layer, may be the critical factor for the inhibition of thromboses. Respective antithrombogenic properties will mainly affect pre-venous microvascular circulation. In detail, they include thrombin-induced endothelial formation of antiaggregatory autacoids from platelet release products, anticoagulatory activation of protein C and absorption of active coagulation factors at endothelial heparan/ATIII complexes as well as release of profibrinolytic plasminogen activator of endothelial origin. The understanding of these complex regulatory functions enables not only a critical evaluation of actually discussed haemostasiologic risk factors (enhanced platelet reactivity, high concentrations of factor VII, VIII, fibrinogen, PAI, ATIII), but also the development of new pharmacologic strategies for prevention of thrombosis.

Published
2004
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