Dokument: Einfluss des HPA-1-Polymorphismus des Integrins αIIbβ3 auf die Plättchenadhäsion an immobilisiertes Fibrinogen unter arteriellen und venösen Blutflussbedingungen in einem In-vitro-Modell
| Titel: | Einfluss des HPA-1-Polymorphismus des Integrins αIIbβ3 auf die Plättchenadhäsion an immobilisiertes Fibrinogen unter arteriellen und venösen Blutflussbedingungen in einem In-vitro-Modell | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=18921 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20110817-090148-4 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Opalka, Sabine [Autor] | |||||||
| Dateien: |
| |||||||
| Beitragende: | Prof. Dr. med. Scharf, Rüdiger E. [Betreuer/Doktorvater] Prof. Dr. med. Hohlfeld, Thomas [Gutachter] | |||||||
| Stichwörter: | HPA-1-Polymorphismus, Integrin αIIbβ3, Plättchenadhäsion, Scherrate | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | - Die Plättchenadhäsion an immobilisiertes Fibrinogen unter arteriellen Blutflussbedingungen wird über das Integrin αIIbβ3 gesteuert, hierbei steigt die Adhäsion sowohl im Zeitverlauf als auch bei steigender Scherrate
- Die spezifische Interaktion zwischen immobilisiertem Fibrinogen und dem Integrin αIIbβ3 wird moduliert durch den HPA-1-Polymorphismus der β-Untereinheit des Integrins αIIbβ3 - Der HPA-1b/1b Genotyp ist assoziiert mit einer erhöhten (relativen) Plättchenadhäsion an immobilisiertes Fibrinogen, dies zeigt sich in einem schnelleren Anstieg der Plättchenadhäsion im Vergleich zu den Genotypen HPA-1a/1a und HPA-1a/1b In der vorliegenden Arbeit zeigt sich, dass insbesondere die HPA-1b-Variante eine gesteigerte Plättchenthrombogenität zur Folge hat. Darüber hinaus wird festgestellt, dass speziell der Genotyp HPA-1b/1b, welcher zu Beginn der Versuche noch die geringste (absolute) Adhäsion zeigt, im Verlauf des größten Adhäsionsanstieg aufweist. Die Ergebnisse unterstützen somit die Hypothese, dass der HPA-1-Polymorphismus des Integrins αIIbβ3 die Plättchenadhäsion an immobilisiertes Fibrinogen beeinflusst und dadurch eine Rolle bei der Entstehung der arteriellen Thrombose spielt. Allerdings lässt sich eine derart starke Assoziation, wie sie in vorangegangenen klinischen Studien festgestellt worden ist, in dieser Arbeit nicht nachweisen. Möglicherweise ist der heterozygote oder homozygote HPA-1b-Genotyp kein eigener Risikofaktor für die Entstehung arterieller Thrombosen, sondern eine zusätzliche Risikodeterminante, welche nur in Kombination mit weiteren (klassischen) Risikofaktoren zum Tragen kommt. | |||||||
| Quelle: | Statistisches Bundesamt (Hrsg.)
Gesundheitswesen, Todesursachen Deutschland 2003 Fachserie 12 / Reihe 4 Wiesbaden 2005; Kap. 2.1.3 Lopez A.D., Murray C.C.J.L. The global burden of disease, 1990-2020 Nat Med 1998; 4: S. 1241-1243 Kroll M.H., Hellums J.D., McIntire L.V., Schafer A.I., Moake J.L. Platelets and shear stress Blood 1996; 88: S. 1525-1541 Lohr M., Keppler B. Innere Medizin - Kompendium für Studium und Klinik, 3. Auflage Urban & Fischer München Jena 2000; S. 88 Lohr M., Keppler B. Innere Medizin - Kompendium für Studium und Klinik, 3. Auflage Urban & Fischer München Jena 2000; S. 103-104 Gawaz M. Das Blutplättchen – Physiologie, Pathophysiologie, Membranrezeptoren, antithrombozytäre Wirkstoffe und Therapie bei koronarer Herzerkrankung Georg Thieme Stuttgart 1999; S. 1-2 Aarts P.A.M.M., Bolhuis P.A., Sakariassen K.S., Heethaar R.M., Sixma J.J. Red blood cell size is important for adherence of blood platelets to artery subendothelium Blood 1983; 62: S. 214-217 Joist J.H., Bauman J.E., Sutera S.P. Platelet adhesion and aggregation in pulsatile shear flow: Effects of red blood cells Thromb Res 1998; 92: S. 47-52 Hellem A.J., Borchgrevink C.F., Ames S.B. The role of red cells in haemostasis: the relation between haematocrit, bleeding time and platelet adhesiveness Brit J Haematol 1961; 7: S. 42-50 Moia M., Vizzotto L., Cattaneo M., Mannucci P.M., Casati S., Ponticelli C. Improvement in the haemostatic defect of uraemia after treatment with recombinant human Erythropoietin Lancet 1987; ii: S. 1227-1229 Weiss H.J., Turitto V.T., Baumgartner H.R. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate-dependent decrease of adhesion in von Willebrand´s disease and the Bernard-Soulier syndrome J Lab Clin Med 1978; 92: S. 750-764 Bonnefoy A., Liu Q., Legrand C., Frojmovic M.M. Efficiency of platelet adhesion to fibrinogen depends on both cell activation and flow Biophys J 2000; 78: S. 2834-2843 Turner N.A., Moake J.L., Kamat S.G., Schafer A.I., Kleiman N.S., Jordan R., McIntire L.V. Comparative real-time effects on platelet adhesion and aggregation under flowing conditions of in vivo aspirin, heparin, and monoclonal antibody fragments against glycoprotein IIb-IIIa Circulation 1995; 91: S. 1354-1362 Goldsmith H.L., Turitto V.T. Rheological aspects of thrombosis and haemostasis: Basic principles and applications Thromb Haemost 1986; 55: S. 415-435 Weiss E.J., Bray P.F., Tayback M., Schulman S.P., Kickler T.S., Becker L.C., Weiss J.L., Gerstenblith G., Goldschmidt-Clermont P.J. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis N Engl J Med 1996; 334: S. 1090-1094 Müller-Berghaus G., Pötzsch B. (Hrsg.) Hämostaseologie - Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik Springer Berlin Heidelberg 1999; S. 15-16 Zotz R.B., Winkelmann B.R., Nauck M., Giers G., Maruhn-Debowski B., März W., Scharf R.E. Polymorphism of platelet membrane glycoprotein IIIa: Human platelet antigen 1b (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in coronary artery disease Thromb Haemost 1998; 79: S. 731-735 Gawaz M. Das Blutplättchen – Physiologie, Pathophysiologie, Membranrezeptoren, antithrombozytäre Wirkstoffe und Therapie bei koronarer Herzerkrankung Georg Thieme Stuttgart 1999; S. 9-10 Alevriadou B.R., Moake J.L., Turner N.A., Ruggeri Z.M., Folie B.J., Phillips M.D., Schreiber A.B., Hrinda M.E., McIntire L.V. Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand Factor binding to platelets Blood 1993; 81: S. 1263-1276 Nieswandt B., Watson S.P. Platelet-collagen interaction: is GPVI the central receptor? Blood 2003; 102: S. 449-461 Massberg S., Gawaz M., Grüner S., Schulte V., Konrad I., Zohlnhöfer D., Heinzmann U., Nieswandt B. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo J Exp Med 2003; 197: S. 41-49 Moroi M., Jung S.M., Nomura S., Sekiguchi S., Ordinas A., Diaz-Ricart M. Analysis of the involvement of the von Willebrand Factor – glycoprotein Ib interaction in platelet adhesion to a collagen-coated surface under flow conditions Blood 1997; 90: S. 4413-4424 Siljander P.R-M., Munnix I.C.A., Smethurst P.A., Deckmyn H., Lindhout T., Ouwehand W.H., Farndale R.W., Heemskerk J.W.M. Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood Blood 2004; 103: S. 1333-1341 Kulkarni S., Dopheide S.M., Yap C.L., Ravanat C., Freund M., Mangin P., Heel K.A., Street A., Harper I.S., Lanza F., Jackson S.P. A revised model of platelet aggregation J Clin Invest 2000; 105: S. 783-791 Gawaz M. Das Blutplättchen – Physiologie, Pathophysiologie, Membranrezeptoren, antithrombozytäre Wirkstoffe und Therapie bei koronarer Herzerkrankung Georg Thieme Stuttgart 1999; S. 30-35 Phillips D.R., Charo I.F., Parise L.V., Fitzgerald L.A. The platelet membrane glycoprotein IIb-IIIa complex Blood 1988; 71: S. 831-843 Kunicki T.J., Pidard D., Rosa J-P., Nurden A.T. The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis Blood 1981; 58: S. 268-278 Fujimura K., Phillips D.R. Calcium cation regulation of glycoprotein IIb-IIIa complex formation in platelet plasma membranes J Biol Chem 1983; 258: S. 10247-10252 Kunicki T.J., Newman P.J. The molecular immunology of human platelet proteins Blood 1992; 80: S. 1386-1404 Lefkovits J., Plow E.F., Topol E.J. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine N Engl J Med 1995; 332: S. 1553-1559 Zotz R.B., Klein M., Dauben H.P., Moser C., Gams E., Scharf R.E. Prospective analysis after coronary-artery bypass grafting: Platelet GP IIIa polymorphism (HPA-1b/PlA2) is a risk factor for bypass occlusion, myocardial infarction, and death Thromb Haemost 2000; 83: S. 404-407 Carter A.M., Ossei-Gerning N., Wilson I.J., Grant P.J. Association of the platelet PlA polymorphism of glycoprotein IIb/IIIa and the fibrinogen Bβ 448 polymorphism with myocardial infarction and extent of coronary artery disease Circulation 1997; 96: S. 1424-1431 Goodall A.H., Curzen N., Panesar M., Hurd C., Knight C.J., Ouwehand W.H., Fox K.M. Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease Eur Heart J 1999; 20: S. 742-747 Woods V.L., Wolff L.E., Keller D.M. Resting platelets contain a substantial centrally located pool of glycoprotein IIb-IIIa complex which may be accessible to some but not other extracellular proteins J Biol Chem 1986; 261: S. 15242-15251 Niiya K., Hodson E., Bader R., Byers-Ward V., Koziol J.A., Plow E.F., Ruggeri Z.M. Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation Blood 1987; 70: S. 475-483 McEver R.P., Baenziger J.U., Majerus P.W. Isolation and structural characterization of the polypeptide subunits of membrane glycoprotein IIb-IIIa from human platelets Blood 1982; 59: S. 80-85 Poncz M., Eisman R., Heidenreich R., Silver S.M., Vilaire G., Surrey S., Schwartz E., Bennett J.S. Structure of the platelet membrane glycoprotein IIb J Biol Chem 1987; 262: S. 8476-8482 McEver R.P., Baenziger N.L., Majerus P.W. Isolation and quantitation of the platelet membrane glycoprotein deficient in thrombasthenia using a monoclonal hybridoma antibody J Clin Invest 1980; 66: S. 1311-1318 Ruoslahti E., Pierschbacher M.D. New perspectives in cell adhesion: RGD and integrins Science 1987; 238: S. 491-497 Weisel J.W., Nagaswami C., Vilaire G., Bennett J.S. Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy J Biol Chem 1992; 267: S. 16637-16643 Farrell D.H., Thiagarajan P., Chung D.W., Davie E.W. Role of fibrinogen α and γ chain sites in platelet aggregation Proc Natl Acad Sci USA 1992; 89: S. 10729-10732 Prasad K.S.S., Andre P., He M., Bao M., Manganello J., Phillips D.R. Soluble CD40 ligand induces β3 integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling Proc Natl Acad Sci USA 2003; 100: S. 12367-12371 Bray P.F. Integrin polymorphisms as risk factors for thrombosis Thromb Haemost 1999; 82: S. 337-344 von dem Borne A.E.G., Décary F. Nomenclature of platelet-specific antigens Transfusion 1990; 30: S. 477 Newman P.J., Derbes R.S., Aster R.H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/ proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing J Clin Invest 1989; 83: S. 1778-1781 Müller-Berghaus G., Pötzsch B. (Hrsg.) Hämostaseologie - Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik Springer Berlin Heidelberg 1999; S. 99 Streifler J.Y., Rosenberg N., Chetrit A., Eskaraev R., Sela B.A., Dardik R., Zivelin A., Ravid B., Davidson J., Seligsohn U., Inbal A. Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism Stroke 2001; 32: S. 2753-2758 Ardissino D., Mannucci P.M., Merlini P.A., Duca F., Fetiveau R., Tagliabue L., Tubaro M., Galvani M., Ottani F., Ferrario M., Corral J., Margaglione M. Prothrombotic genetic risk factors in young survivors of myocardial infarction Blood 1999; 94: S. 46-51 Walter D.H., Schächinger V., Elsner M., Dimmeler S., Zeiher A.M. Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis Lancet 1997; 350: S. 1217-1219 Herrmann S-M., Poirier O., Marques-Vidal P., Evans A., Arveiler D., Luc G., Emmerich J., Cambien F. The leu33/pro polymorphism (PlA1/PlA2) of the glycoprotein IIIa (GPIIIa) receptor is not related to myocardial infarction in the ECTIM study Thromb Haemost 1997; 77: S. 1179-1181 Ridker P.M., Hennekens C.H., Schmitz C., Stampfer M.J., Lindpaintner K. PlA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis Lancet 1997; 349: S. 385-388 Scaglione L., Bergerone S., Gaschino G., Imazio M., Maccagnani A., Gambino R., Cassader M., Di Leo M., Macchia G., Brusca A., Pagano G., Cavallo-Perin P. Lack of relationship between the PlA1/PlA2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction Eur J Clin Invest 1998; 28: S. 385-388 Böttiger C., Kastrati A., Koch W., Mehilli J., Seidl H., Schömig K., von Beckerath N., Schömig A. HPA-1 and HPA-3 polymorphisms of the platelet fibrinogen receptor and coronary artery disease and myocardial infarction Thromb Haemost 2000; 83: S. 559-562 Durante-Mangoni E., Davies G.J., Ahmed N., Ruggiero G., Tuddenham E.G. Coronary thrombosis and the platelet glycoprotein IIIa gene PlA2 polymorphism Thromb Haemost 1998; 80: S. 218-219 Samani N.J., Lodwick D. Glycoprotein IIIa polymorphism and risk of myocardial infarction Cardiovasc Res 1997; 33: S. 693-697 Scharf R.E., Zotz R.B. Blood platelets and myocardial infarction: Do hyperactive platelets really exist? Transfus Med Hemother 2006; 33: S. 189-199 Sajid M., Vijayan K.V., Souza S., Bray P.F. PlA polymorphism of integrin β3 differentially modulates cellular migration on extracellular matrix proteins Arterioscler Thromb Vasc Biol 2002; 22: S. 1984-1989 Stoldt V.R., Peveling J., Loncar R., Beck A., Aurich V., Scharf R.E. Evaluation of platelet thrombus formation under flow Blood 2005; 106: S. 3954 Zotz R.B., Winkelmann B.R., Müller C., Boehm B.O., März W., Scharf R.E. Association of polymorphisms of platelet membrane integrins αIIbβ3 (HPA-1b/PlA2) and α2β1 (α2807TT) with premature myocardial infarction J Thromb Haemost 2005; 3: S. 1522-1529 Vijayan K.V., Goldschmidt-Clermont P.J., Roos C., Bray P.F. The PlA2 polymorphism of integrin β3 enhances outside-in signaling and adhesive functions J Clin Invest 2000; 105: S. 793-802 Meiklejohn D.J., Urbaniak S.J., Greaves M. Platelet glycoprotein IIIa polymorphism HPA 1b (PlA2): No association with platelet fibrinogen binding Brit J Haematol 1999; 105: S. 664-666 Bennett J.S., Vilaire G., Catella-Lawson F., Rut A.R., FitzGerald G. The PlA2 alloantigen does not alter the affinity of GPIIb-IIIa for fibrinogen or RGD-containing peptides Blood 1997; 90: S. 154a Michelson A.D., Furman M.I., Goldschmidt-Clermont P., Mascelli M.A., Hendrix C., Coleman L., Hamlington J., Barnard M.R., Kickler T., Christie D.J., Kundu S., Bray P.F. Platelet GP IIIa PlA polymorphisms display different sensitivities to agonists Circulation 2000; 101: S. 1013-1018 Feng D.L., Lindpaintner K., Larson M.G., Rao V.S., O´Donnell C.J., Lipinska I., Schmitz C., Sutherland P.A., Silbershatz H., D´Agostino R.B., Muller J.E., MyersR.H., Levy D., Tofler G.H. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism The Framingham offspring study Arterioscler Thromb Vasc Biol 1999; 19: S. 1142-1147 Dise C.A., Burch J.W., Goodman D.B.P. Direct interaction of mepacrine with erythrocyte and platelet membrane phospholipid J Biol Chem 1982; 257: S. 4701-4704 Müller-Berghaus G., Pötzsch B. (Hrsg.) Hämostaseologie - Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik Springer Berlin Heidelberg 1999; S. 65 Grabowski E.F. Platelet aggregation in flowing blood at a site of injury to an endothelial cell monolayer: Quantitation and real-time imaging with the TAB monoclonal antibody Blood 1990; 75: S. 390-398 Skaer R.J., Flemans R.J., McQuilkan S. Mepacrine stains the dense bodies of human platelets and not platelet lysosomes Brit J Haematol 1981; 49: S. 435-438 Wall J.E., Buijs-Wilts M., Arnold J.T., Wang W., White M.M., Jennings L.K., Jackson C.W. A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents Brit J Haematol 1995; 89: S. 380-385 Robinson M., Machin S., Mackie I., Harrison P. In vivo biotinylation studies: Specificity of labelling of reticulated platelets by thiazole orange and mepacrine Brit J Haematol 2000; 108: S. 859-864 Lorez H.P., Da Prada M., Rendu F., Pletscher A. Mepacrine, a tool for investigating the 5-hydroxytryptamine organelles of blood platelets by fluorescence microscopy J Lab Clin Med 1977; 89: S. 200-206 Da Prada M., Pletscher A. Accumulation of basic drugs in 5-hydroxytryptamine storage organelles of rabbit blood platelets Eur J Pharmacol 1975; 32: S. 179-185 Read N.G., Trist D.G. The uptake of mepacrine by horse polymorphonuclear leucocytes in vitro J Pharm Pharmacol 1982; 34: S. 711-714 Balasubramanian V., Grabowski E., Bini A., Nemerson Y. Platelets, circulating tissue factor, and fibrin colocalize in ex vivo thrombi: Real-time fluorescence images of thrombus formation and propagation under defined flow conditions Blood 2002; 100: S. 2787-2792 Greco N.J., Tenner T.E. Jr., Tandon N.N., Jamieson G.A. PPACK-thrombin inhibits thrombin-induced platelet aggregation and cytoplasmic acidification but does not inhibit platelet shape change Blood 1990; 75: S. 1983-1990 Kettner C., Shaw E. D-Phe-Pro-ArgCH2Cl – A selective affinity label for thrombin Thromb Res 1979; 14: S. 969-973 Lyon M.E., Fine J.S., Henderson P.J., Lyon A.W. D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK): Alternative anticoagulant to heparin salts for blood gas and electrolyte specimens Clin Chem 1995; 41: S. 1038-1041 Savage B., Shattil S.J., Ruggeri Z.M. Modulation of platelet function through adhesion receptors J Biol Chem 1992; 267: S. 11300-11306 Müller-Berghaus G., Pötzsch B. (Hrsg.) Hämostaseologie - Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik Springer Berlin Heidelberg 1999; S. 285-286 Karow T., Lang-Roth R. Allgemeine und spezielle Pharmakologie und Toxikologie - Vorlesungsorientierte Darstellung und klinischer Leitfaden 2004 Eigenverlag Pulheim 2004; S. 302-304 Loncar R. Functional relevance of HPA-1 and α2 807C/T platelet receptor polymorphisms under standardized in-vitro blood flow conditions Universität Düsseldorf, Medizinische Fakultät, Habilitationsschrift, 2006 Reiner A.P., Kumar P.N., Schwartz S.M., Longstreth W.T. Jr., Pearce R.M., Rosendaal F.R., Psaty B.M., Siscovick D.S. Genetic variants of platelet glycoprotein receptors and risk of stroke in young women Stroke 2000; 31: S. 1628-1633 Roest M., Banga J.D., Grobbee D.E., de Groot P.G., Sixma J.J., Tempelman M.J., van der Schouw Y.T. Homozygosity for 807 T polymorphism in α2 subunit of platelet α2β1 is associated with increased risk of cardiovascular mortality in high-risk women Circulation 2000; 102: S. 1645-1650 Zaidi T.N., McIntire L.V., Farrell D.H., Thiagarajan P. Adhesion of platelets to surface-bound fibrinogen under flow Blood 1996; 88: S. 2967-2972 Müller-Berghaus G., Pötzsch B. (Hrsg.) Hämostaseologie - Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik Springer Berlin Heidelberg 1999; S. 29 HPA-1 polymorphism of αIIbβ3 modulates platelet adhesion onto immobilized fibrinogen in an in-vitro flow system Loncar R., Stoldt V., Hellmig S., Zotz R.B., Mihalj M., Scharf R.E. Thromb J 2007; 5: S. 2 Steering committee of the physicians´ health study research group Final report on the aspirin component of the ongoing physicians´ health study N Engl J Med 1989; 321: S. 129-135 Lewis H.D.Jr., Davis J.W., Archibald D.G., Steinke W.E., Smitherman T.C., Doherty J.E.III., Schnaper H.W., LeWinter M.M., Linares E., Pouget J.M., Sabharwal S.C., Chesler E., DeMots H. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina Results of a Veterans Administration Cooperative Study N Engl J Med 1983; 309: S. 396-403 The RISC Group Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease Lancet 1990; 336: S. 827-830 Karow T., Lang-Roth R. Allgemeine und spezielle Pharmakologie und Toxikologie - Vorlesungsorientierte Darstellung und klinischer Leitfaden 2004 Eigenverlag Pulheim 2004; S. 299 Karow T., Lang-Roth R. Allgemeine und spezielle Pharmakologie und Toxikologie - Vorlesungsorientierte Darstellung und klinischer Leitfaden 2004 Eigenverlag Pulheim 2004; S. 552-553 Cooke G.E., Bray P.F., Hamlington J.D., Pham D.M., Goldschmidt-Clermont P.J. PlA2 polymorphism and efficacy of aspirin Lancet 1998; 351: S. 1253 Wheeler G.L., Braden G.A., Bray P.F., Marciniak S.J., Mascelli M.A., Sane D.C. Reduced inhibition by abciximab in platelets with the PlA2 polymorphism Am Heart J 2002; 143: S. 76-82 | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Hämostaseologie und Transfusionsmedizin | |||||||
| Dokument erstellt am: | 17.08.2011 | |||||||
| Dateien geändert am: | 17.08.2011 | |||||||
| Promotionsantrag am: | 07.01.2011 | |||||||
| Datum der Promotion: | 03.08.2011 |
