Search

Your search keyword '"Pabinger I."' showing total 31 results
Start Over Author "Pabinger I." Journal annals of hematology
31 results on '"Pabinger I."'

13. Abstract

Author

Mache, Ch., Urban, Ch., Sauer, H., Brandesky, G., Meßner, H., Grienberger, H., Becker, H., Slave, I., Hauer, Ch., Pakisch, B., Oberbauer, R., Mokry, M., Ebner, F., Kleinert, R., Schiller, D., Kasparu, H., Schneider, G., Sega, W., Lutz, D., Mader, R. M., Steger, G. G., Sieder, A. E., Ovissi, L., Roth, E., Hamilton, G., Jakesz, R., Rainer, H., Schenk, T., Kornek, G., Schulz, F., Depisch, D., Rosen, H., Sebesta, Ch., Scheithauer, W., Locker, G. J., Czernin, J., Derfler, K., Gnant, M., Schiessel, R., Petru, E., Pickel, H., Heydarfadai, M., Lahousen, M., Haas, J., Sagaster, P., Flamm, J., Umek, H., Essl, R., Teich, G., Micksche, M., Ludwig, H., Ambros, P. F., Lestou, V., Strehl, S., Mann, G., Gadner, H., Eibl, B., Greiter, E., Grünewald, K., Gastl, G., Thaler, J., Aulitzky, W., Lion, T., Henn, T., Gaiger, A., Hofmann, J., Wolf, A., Spitaler, M., Ludescher, Christof, Grunicke, H., Mitterbauer, G., Stangl, E., Geissler, K., Jäger, U., Lechner, K., Mannhalter, C., Haas, Oskar A., Tirita, Anthi, Kahls, P., Haas, O., Hinterberger, W., Linkesch, W., Pober, Michael, Fae, Ingrid, Kyrle, Alexander, Neumeister, Andrea, Panzer, Simon, Kandioler, D., End, A., Grill, R., Karlic, H., Inhauser, T., Chott, A., Pirc-Danoewinata, H., Klepetko, W., Heinz, R., Hopfinger-Limberger, G., Koller, E., Schneider, B., Pittermann, E., Lorber, C., Eichinger, S., Neumann, E., Weidinger, J., Gisslinger, H., Bedford P., Jones D., Cawley J., Catovsky D., Bevan P., Scherrer, R., Bettelheim, P., Knöbl, P., Kyrie, P. A., Lazcika, K., Schwarzinger, I., Sillaber, C., Watzke, H., Dávid, M., Losonczy, H., Matolcsy, A., Papp, M., Prischl, F. C., Schwarzmeier, J. D., Zoubek, Andreas, Harbott, Jochen, Ritterbach, Jutta, Ritter, Jörg, Sillaber, Ch., Agis, H., Spanblöchl, E., Sperr, W. R., Valent, P., Czerwenka, K., Virgolini, I., Li, S. R., Müller, M., Wrann, M., Gaggl, S., Fasching, B., Herold, M., Geissler, D., Nachbaur, D., Huber, Ch., Schwaighofer, H., Pichl, M., Niederwieser, D., Gilly, B., Weissel, H., Lorber, Ch., Schwarzmeier, J., Gasché, C., Reinisch, W., Hilgarth, M., Keil, F., Thomssen, C., Kolb, H. J., Holler, E., Wilmanns, W., Tilg, H., Gächter, A., Panzer-Grümayer, E. R., Majdic, O., Kersey, J. H., Petzer, A. L., Bilgeri, R., Zilian, U., Geisen, F. H., Haun, M., Konwalinka, G., Fuchs, D., Zangerle, R., Artner-Dworzak, E., Weiss, G., Fritsch, P., Tilz, G. P., Dierich, M. P., Wachter, H., Schüller, J., Czejka, M. J., Jäger, W., Meyer, B., Weiss, C., Schernthaner, G., Marosi, Ch., Onderka, E., Schlögl, B., Maca, T., Hanak, R., Mannhalter, Ch., Brenner, B., Mayer, R., Langmann, A., Langmann, G., Slave, J., Poier, E., Stücklschweiger, G., Hackl, A., Fritz, A., Pabinger, I., Willfort, A., Groiss, E., Bernhart, M., Waldner, R., Krieger, O., Nowotny, H., Strobl, H., Michlmayr, G., Mistrik, M., lstvan, L., Kapiotis, S., Laczika, K., Speiser, W., Granena, A., Hermans, J., Zwaan, F., Gratwohl, A., Labar B., Mrsić M., Nemet D., Bogdanić V., Radman I., Zupančić-Šalek Silva, Kovačević-Metelko Jasna, Aurer I., Forstinger, C., Scholten, C., Kier, P., Kalhs, P., Schwinger, W., Slavc, I., Lackner, H., Nussbaumer, W., Fritsch, E., Fink, M., Zechner, O., Kührer, I., Kletter, V., Frey, S., Leitgeb, C., Fritz, E., Silly, H., Brezinschek, R., Kuss, I., Stöger, H., Schmid, M., Samonigg, H., Wilders-Truschnig, M., Schmidt, F., Bauernhofer, T., Kasparek, A. K., Ploner, F., Stoeger, H., Moser, R., Leikauf, W., Klemm, F., Pfeffel, F., Niessner, H., Poschauko, H., Pojer, E., Locker, G. J., Braun, J., Gnant, M. F. X., Michl, I., Pirker, R., Liebhard, A., Zielinski, C., Dittrich, C., Bernát, S. I., Pongrácz, E., Kastner, J., Raderer, M., Jorbenyi, Z., Yilmaz, A., Suardet, L., Lahm, H., Odartchenko, N., Varga, Gy., Sréter, L. A., Oberberg, D., Berdel, W. E., Budiman, R., Brand, C., Berkessy, S., Radványi, G., Pauker, Zs., Nagy, Zs., Karádi, Å., Serti, S., Hainz, R., Kirchweger, P., Prager, C., Prada, J., Neifer, S., Bienzle, U., Kremsner, P., Kämmerer, B., Vetterlein, M., Pohl, W., Letnansky, K., Imre, S. G., Parkas, T., Lakos, Zs., Kiss, A., Telek, B., Felszeghy, E., Kelemen, E., Rak, K., Pfeilstöcker, M., Reisner, R., Salamon, J., Georgopoulos, A., Feistauer, S., Georgopoulos, M., Graninger, W., Klinda, F., Hrubisko, M., Sakalova, A., Weißmann, A., Röhle, R., Fortelny, R., Gutierrez, F., Fritsch, G., Printz, D., Buchinger, P., Buchinger, P., Hoecker, P., Peters, C., Gebauer, E., Katanić, D., Nagy, Á., Szomor, Á., Med. J., Batinić D., Užaervić B., Marušić M., Kovačoević-Metelko Jasminka, Jakić-Razumović Jasminka, Kovačević-Metelko Jasminka, Zuoancić-Šalek Silva, Ihra, G. C., Reinisch, W. W., Hilgarth, M. F., Schwarzmeier, I. D., Várady, E., Molnár, Z. S., Fleischmann, T., Borbényi, Z., Bérczi, M., István, L., Szerafin, L., Jakó, J., Bányai, A., Dankó, K., Szegedi, Gy., Neubauer, M., Frudinger, A., Scholten, Ch., Forstinger, Ch., Dobrić I., Willheim, M., Szépfalusi, Z., Mader, R., Boltz, G., Schwarzmeier, J. D., Nahajevszky, S., Téri, N., Póth, I., Nagy, P., Smanykó, D., Babicz, T., Ujj, Gy., Iványi, J. L., Tóth, F. D., Kiss, J., Konja, J., Petković, I., Kardum, I., Kaštelan, M., Kelečić, J., Feminić, R., Djermanović, M., Bilić, E., Jakovljević, G., Peter, B., Gredelj, G., Senji, P., Thalhammer, F., Floth, A., Etele-Hainz, A., Kainberger, F., Radaszkiewicz, T., Kierner, H., Mód, Anna, Pitlik, E., Gottesman, M., Magócsi, Mária, Sarkadi, B., Knapp, S., Purtscher, B., DelleKarth, G., Jaeger, U., Krieger, O., Berger, W., Elbling, L., Ludescher, C., Hilbe, W., Eisterer, W., Preuß, E., Izraeli, S., Janssen, J. W. G., Walther, J. U., Kovar, H., Ludwig, W. D., Rechavi, G., Bartram, C. R., Rehberger, A., Mittermayer, F., Schauer, E., Kokoschka, E. M., Kammerer, B., Kokron, E., Desser, L., Abdul-Hamid, G., Kroschinksky, F., Luther, Th., Fischer, H., Nowak, R., Wolf, H., Fleischer, J., Wichmann, G., Albercht, S., Adorf, D., Kaboth, W., Nerl, C., Aman, J., Rudolf, G., Peschel, C., Anders, O., Burstein, Ch., Ernst, B., Steiner, H., Konrad, H., Annaloro, U. P., Mozzana, C., Butti, R., Della, C., Volpe A., Soligo D., Uderzo M., Lambertenghi-Deliliers G., Ansari, H., Dickson, D., Hasford, J., Hehlmann, R., Anyanwu, E., Krysa, S., Bülzebrück, H., Vogt-Moykopf, I., Arning, M., Südhoff, Th., Kliche, K. O., Wehmeier, A., Schneider, W., Arnold, R., Bunjes, D., Hertenstein, B., Hueske, D., Stefanic, M., Theobald, M., Wiesneth, M., Heimpel, H., Waldmann, H., Arseniev, L., Bokemeyer, C., Andres, J., Könneke, A., Papageorgiou, E., Kleine, H. -D., Battmer, K., Südmeyer, I., Zaki, M., Schmoll, H. -J., Stangel, W., Poliwoda, H., Link, H., Aul, C., Runde, V., Heyll, A., Germing, U., Gattermann, N., Ebert, A., Feinendegen, L. E., Huhn, D., Bergmann, L., Dönner, H., Hartlapp, J. H., Kreiter, H., Schuhmacher, K., Schalk T., Sparwasser C., Peschel U., Fraaß C. Huber, HIadik, F., Kolbe, K., Irschick, E., Bajko, G., Wozny, T., Hansz, J., Bares, R., Buell, U., Baumann, I., Harms, H., Kuse, R., Wilms, K., Müller-Hermelink, H. K., Baurmann, H., Cherif, D., Berger, R., Becker, K., Zeller, W., Helmchen, U., Hossfeld, D. K., Bentrup, I., Plusczyk, T., Kemkes-Matthes, B., Matthes, K., Bentz, M., Speicher, M., Schröder, M., Moos, M., Döhner, H., Lichter, P., Stilgenbauer, S., Korfel, A., Harnoss, B. -M., Boese-Landgraf, J., May, E., Kreuser, E. -D., Thiel, E., Karacas, T., Jahn, B., Lautenschläger, G., Szepes, S., Fenchel, K., Mitrou, P. S., Hoelzer, D., Heil, G., Lengfelder, E., Puzicha, E., Martin, H., Beyer, J., Kleiner, S., Strohscheer, I., Schwerdtfeger, R., Schwella, N., Schmidt-Wolf, I., Siegert, W., Weyer, C., arzen, G., Risse, G., Miksits, K., Farshidfar, G., Birken, R., Schilling, C. v., Brugger, W., Holldack, J., Mertelsmann, R., Kanz, L., Blanz, J., Mewes, K., Ehninger, G., Zeller, K. -P., Böhme. A., Just G., Bergmann. L., Shah P., Hoelzer D., Stille W., Bohlen, H., Hopff, T., Kapp, U., Wolf, J., Engert, A., Diehl, V., Tesch, H., Schrader, A., van Rhee, J., Köhne-Wömpner, H., Bokemeyer', C., Gonnermann, D., Harstrick, A., Schöffski, P., van Rhee, J., Schuppert, F., Freund, M., Boos, J., Göring, M., Blaschke, G., Borstel, A., Franke, A., Hüller, G., Uhle, R., Weise, W., Brach, Marion A., Gruss, Hans-Jürgen, Herrmann, Friedhelm, deVos, Sven, Brennscheidt, Ulrich, Riedel, Detlev, Klch, Walter, Bonlfer, Renate, Mertelsmann, Roland, Brieaer, J., Appelhans, H., Brückner, S., Siemens, HJ., Wagner, T., Moecklin, W., Mertelsmann, R., Bertz, H., Hecht, T., Mertelsmann, R., Bühl, K., Eichelbaum, M. G., Ladda, E., Schumacher, K., Weimer, A., Bühling, F., Kunz, D., Lendeckel, U., Reinhold, D., Ulmer, A. J., Flad, H. -D., Ansorge, S., Bühring, Hans-Jörg, Broudy¶, Virginia C., Ashman§, Leonie K., Burk, M., Kunecke, H., Dumont, C., Meckenstock, G., Volmer, M., Bucher, M., Manegold, C., Krenpien, B., Fischer, J. R., Drings, P., Bückner, U., Donhuijsen-Ant, R., Eberhardt, B., Westerhausen, M., Busch, F. W., Jaschonek, K., Steinke, B., Calavrezos, A., Hausmann, K., Solbach, M., Woitowitz, H. -P., Hilierdal, G., Heilmann, H. -P., Chen, Z. J., Frickhofen, N., Ellbrück, D., Schwarz, T. F., Körner, K., Wiest, C., Kubanek, B., Seifried, E., Claudé, R., Brücher, J., Clemens, M. R., Bublitz, K., Bieger, O., Schmid, B., Clemetson, K. J., Clemm, Ch., Bamberg, M., Gerl, A., Weißbach, L., Danhauser-Riedl, S., Schick, H. D., Bender, R., Reuter, M., Dietzfelbinger, H., Rastetter, J., Hanauske, A. -R., Decker, Hans-Jochen, Klauck, Sabine, Seizinger, Bernd, Denfeld, Ralf, Pohl, Christoph, Renner, Christoph, Hombach, Andreas, Jung, Wolfram, Schwonzen, Martin, Pfreundschuh, Michael, Derigs, H. Günter, Boswell, H. Scott, Kühn, D., Zafferani, M., Ehrhardt, R., Fischer, K., Schmitt, M., Witt, B., Ho, A. D., Haas, R., Hunstein, W., Dölken, G., Finke, J., Lange, W., Held, M., Schalipp, E., Fauser, A. A., Mertelsmann, R., Donhuijsen, K., Nabavi, D., Leder, L. D., Haedicke, Ch., Freund, H., Hattenberger, S., Dreger, Peter, Grelle, Karen, Schmitz, Norbert, Suttorp, Meinolf, Müller-Ruchholtz, Wolfgang, Löffler, Helmut, Dumoulin, F. L., Jakschies, D., Walther, M., Hunger, P., Deicher, H., von Wussow, P., Dutcher, J. P., Ebell, W., Bender-Götze, C., Bettoni, C., Niethammer, D., Reiter, A., Sauter, S., Schrappe, M., Riehm, H., Niederle, N., Heidersdorf, H., Müller, M. R., Mengelkoch, B., Vanhoefer, U., Stahl, M., Budach, V., loehren, B., Alberti, W., Nowrousian, M. R., Seeber, S., Wilke, H., Stamatis, G., Greschuchna, D., Sack, H., Konietzko, N., Krause, B., Dopfer, R., Schmidt, H., Einsele, H., Müller, C. A., Goldmann, S. F., Grosse-Wilde, H., Waller, H. D., Libal, B., Hohaus, S., Gericke, G., von Eiff, M., Oehme, A., Roth, B., van de Loo, J., von Eiff, K., Pötter, R., Weiß, H., Suhr, B., Koch, P., Roos, H., van de Loo, J., Meuter, V., Heissig, B., Schick, F., Duda, S., Saal, J. G., Klein, R., Steidle, M., Eisner, S., Ganser, A., Seipelt, G., Leonhardt, M., Engelhard, M., Brittinger, G., Gerhartz, H., Meusers, P., Aydemir, Ü., Tintrup, W., Tiemann, H., Lennert, K., Esser, B., Hirsch, F. W., Evers, C., Riess, H., Lübbe, A., Greil, R., Köchling, A., Digel, D., Bross, K. J., Dölken, G., Mertelsmann, R., Gencic S., Ostermann, M., Baum, R. P., Fiebig, H. H., Berger, D. P., Dengler, W. A., Winterhalter, B. R., Hendriks, H., Schwartsmann, G., Pinedo, H. M., Ternes, P., Mertelsmann, R., Dölken, G., Fischbach, W., Zidianakis, Z., Lüke, G., Kirchner, Th., Mössner, J., Fischer, Thomas, Haque, Saikh J., Kumar, Aseem, Rutherford, Michael N., Williams, Bryan R. G., Flohr, T., Decker, T., Thews, A., Hild, F., Dohmen, M., von Wussow, P., Grote-Metke, A., Otremba, B., Fonatsch, C., Binder, T., Imhof, C., Feller, A. C., Fruehauf, S., Moehle, R., Hiddemann Th., Büchner M. Unterhalt, Wörmann, B., Ottmann, O. G., Verbeek, G. W., Seipelt A. Maurer, Geissler, G., Schardt, C., Reutzel, R., Hiddemann, W., Maurer, A., Hess, U., Lindemann, A., Frisch, J., Schulz, G., Mertelsmann, R., Hoelzer, P., Gassmann, W., Sperling, C., Uharek, L., Becher, R., Weh, H. J., Tirier, C., Hagemann, F. G., Fuhr, H. G., Wandt, H., Sauerland, M. C., Gause, A., Spickermann, D., Klein, S., Pfreund-schuh, M., Gebauer, W., Fallgren-Gebauer, E., Geissler, R. G., Mentzel, U., Kleiner, K., Rossol, R., Guba, P., Kojouharoff, G., Gerdau, St., Körholz, D., Klein-Vehne, A., Burdach, St., Gerdemann M., Maurer J., Gerhartz, H. H., Schmetzer, H., Mayer, P., Clemm, C., Hentrich, M., Hartenstein, R., Kohl, P., Gieseler, F., Boege, F., Enttmann, R., Meyer, P., Glass, B., Zeis, M., Loeffler, H., Mueller-Ruchholtz, W., Görg, C., Schwerk, W. B., Köppler, H., Havemann, K., Goldschmitt, J., Goldschmidt, H., Nicolai, M., Richter, Th., Blau, W., Hahn, U., Kappe, R., Leithäuser, F., Gottstein, Claudia, Schön, Gisela, Dünnebacke, Markus, Berthold, Frank, Gramatzki, M., Eger, G., Geiger, M., Burger, R., Zölch, A., Bair, H. J., Becker, W., Griesinger, F., Elfers, H., Griesser, H., Grundner-Culemann, E., Neubauer, V., Fricke, D., Shalitin, C., Benter, T., Mertelsmann, R., Dölken, Gottfried, Mertelsmann, Roland, Günther, W., Schunmm, M., Rieber, P., Thierfelder, S., Gunsilius, E., Kirstein, O., Bommer, M., Serve, H., Hülser, P. -J., Del Valle F., Fischer J. Th., Huberts H., Kaplan E., Haase, D., Halbmayer, W. -M., Feichtinger, Ch., Rubi, K., Fischer, M., Hallek, M., Lepislo, E. M., Griffin, J. D., Emst, T. J., Druker, B., Eder, M., Okuda, K., D.Griffin, J., Kozłowska-Skrzypczak, K., Meyer, B., Reile, D., Scharnofske, M., Hapke, G., Aulenbacher, P., Havemann, K., Becker, N., Scheller, S., Zugmaier, G., Pralle, H., Wahrendorf, J., Heide, Immo, Thiede, Christian, de Kant, Eric, Neubauer, Andreas, Herrmann, Richard, Rochlitz, Christoph, Heiden, B., Depenbrock, H., Block, T., Vogelsang, H., Schneider, P., Fellbaum, Ch., Heidtmann, H. -H., Blings, B., Havemann, K., Fackler-Schwalbe, E., Schlimok, G., Lösch, A., Queißer, W., Löffler, B., Kurrle, E., Chadid, L., Lindemann, A., Mertelsmann, R., Nicolay, U., Gaus, W., Heinemann, V., Jehn, U., Gleixner, B., Wachholz, W., Scholz, P., Plunkett, W., Heinze, B., Novotny, J., Hess, Georg, Gamm, Heinold, Seliger, Barbara, Heuft, H. G., Oettle, H., Zeiler, T., Eckstein, R., Heymanns, J., Havemann, K., Hladik, F., Hoang-Vu, C., Horn, R., Cetin, Y., Scheumann, G., Dralle, H., Köhrle, J., von zur Mühlen, A., Brabant, G., Hochhaus, A., Mende, S., Simon, M., Fonatsch, Ch., Heinze, B., Georgii, A., Hötzl, Ch., Hintermeier-Knabe, R., Kempeni, J., Kaul, M., Hoetzl, Ch., Clemm, Ch., Lauter, H., Hoffknecht, M. M., Eckardt, N., Hoffmann-Fezer, G., Gall, C., Kranz, B., Zengerle, U., Pfoersich, M., Birkenstock, U., Pittenann, E., Heinz, B., Hosten, N., Schörner, W., Kirsch, A., Neumann, K., Felix, R., Humpe, A., Kiss, T., Trümper, L. H., Messner, H. A., Hundt, M., Zielinska-Skowronek, M., Schubert, J., Schmidt, R. E., Huss, R., Storb, R., Deeg, H. J., Issels, R. D., Bosse, D., Abdel-Rahman, S., Jaeger, M., Söhngen, D., Weidmann, E., Schwulera, U., Jakab, I., Fodor, F., Pecze, K., Jaques, G., Schöneberger, H. -J., Wegmann, B., Grüber, A., Bust, K., Pflüger, K. -H., Havemann, K., Faul, C., Wannke, B., Scheurlen, M., Kirchner, M., Dahl, G., Schmits, R., Fohl, C., Kaiser, U., Tuohimaa, P., Wollmer, E., Aumüller, G., Havemann, K., Kolbabek, H., Schölten, C., Popov-Kraupp, B., Emminger, W., Hummel, M., Pawlita, M., v.Kalle, C., Dallenbach, F., Stein, H., Krueger, G. R. F., Müller-Lantzsch, N., Kath, R., Höffken, K., Horn, G., Brockmann, P., Keilholz, U., Stoelben, E., Scheibenbogen, C., Manasterski, M., Tilgen, W., Schlag, P., Görich, J., Kauffmann, G. W., Kempter, B., Rüth, S., Lohse, P., Khalil, R. M., Hültner, L., Mailhammer, R., Luz, A., Hasslinger, M. -A., Omran, S., Dörmer, P., Kienast, J., Kister, K. P., Seifarth, W., Klaassen, U., Werk, S., Reiter, W. W., Klein, G., Beck-Gessert, S., Timpl, R., Hinrichs, H., Lux, E., Döring, G., Scheinichen, D., Döring, G., Wernet, P., Vogeley, K. T., Richartz, G., Südhoff, T., Horstkotte, D., Klocker, J., Trotsenburg, M. v., Schumer, J., Kanatschnig, M., Henning, K., Knauf, W. U., Pottgießer, E., Raghavachar, A., Zeigmeister, B., Bollow, M., Schilling, A., König, H., Koch, M., Volkenandt, M., Seger, Andrea, Banerjee, D., Vogel, J., Bierhoff, E., Heidi, G., Neyses, L., Bertino, J., Kocki, J., Rozynkowa, D. M., M.Rupniewska, Z., Wojcierowski, J., König, V., Hopf, U., Koenigsmann, M., Streit, M., Koeppen, K. M., Martini, I., Poppy, U., Hardel, M., Havemann, K., Havemann, K., Clemm, Ch., Wendt, Th., Gauss, J., Kreienberg, R., Hohenfellner, R., Krieger, O., Istvan, L., Komarnicki, M., Kazmierczak, M., Haertle, D., Korossy, P., Haus, S. Kotlarek, Gabryś, K., Kuliszkiewicz-Janus, M., Krauter, J., Westphal, C., Werner, K., Lang, P., Preissner, K. T., Völler, H., Schröder, K., Uhrig, A., Behles, Ch., Seibt-Jung, H., Besserer, A., Kreutzmann, H., Kröning, H., Kähne, T., Eßbach, U., Kühne, W., Krüger, W. H., Krause, K., Nowicki, B., Stockschläder, M., Peters, S. O., Zander, A. R., Kurowski, V., Schüler, C., Höher, D., Montenarh, M., Lang, W., Schweiger, H., Dölken, Gottfried, Lege, H., Dölken, G., Wex, Th., Frank, K., Hastka, J., Bohrer, M., Leo, R., Peest, D., Tschechne, B., Atzpodien, J., Kirchner, H., Hein, R., Hoffmann, L., Stauch, M., Franks, C. R., Palmer, P. A., Licht, T., Mertelsmann, R., Liersch, T., Vehmeyer, K., Kaboth, U., Maschmeyer, G., Meyer, P., Helmerking, M., Schmitt, J., Adam, D., Prahst, A., Hübner, G., Meisner, M., Seifert, M., Richard, D., Yver, A., Spiekermann, K., Brinkmann, L., Battmer, K., Krainer, M., Löffel, J., Stahl, H., Wust, P., Lübbert, M., Schottelius, A., Mertelsmann, R., Henschler, R., Mertelsmann, R., Mapara, M. Y., Bargou, R., Zugck, C., Krammer, P. H., Dörken, B., Maschek, Hansjörg, Kaloutsi, Vassiliki, Maschek, Hansjörg, Gormitz, Ralf, Meyer, P., Kuntz, B. M. E., Mehl, B., Günther, I., Bülzebruck, H., Menssen, H. D., Mergenthaler, H. -G., Dörmer, P., Heusers, P., Zeller, K. -P., Enzinger, H. M., Neugebauer, T., Klippstein, T., Burkhardt, K. L., Putzicha, E., Möller, Peter, Henne, Christof, Eichelmann, Anette, Brüderlein, Silke, Dhein, Jens, Möstl, M., Krieger, O., Mucke, H., Schinkinger, M., Moiling, J., Daoud, A., Willgeroth, Ch., Mross K., Bewermeier P., Krüger W., Peters S., Berger C., Bohn, C., Edler, L., Jonat, W., Queisser, W., Heidemann, E., Goebel, M., Hamm, K., Markovic-Lipkovski, J., Bitzer, G., Müller, H., Oethinger, M., Grießhammer, M., Tuner, I., Musch E., Malek, M., Peter-Katalinic, J., Hügl, E., Helli, A., Slanicka, M., Filipowicz, A., Nissen, C., Speck, B., Nehls, M. C., Grass, H. -J., Dierbach, H., Mertelsmann, R., Thaller, J., Fiebeler, A., Schmidt, C. A., O'Bryan, J. P., Liu, E., Ritter, M., de Kant, E., Brendel, C., He, M., Dodge, R., George, S., Davey, F., Silver, R., Schiffer, C., Mayer, R., Ball, E., Bloomfield, C., Ramschak, H., Tiran, A., Truschnig-Wilders, M., Nizze, H., Bühring, U., Oelschlägel, U., Jermolow, M., Oertel, J., Weisbach, V., Zingsem, J., Wiens, M., Jessen, J., Osthoff, K., Timm, H., Wilborn, F., Bodak, K., Langmach, K., Bechstein, W., Blumhardt, G., Neuhaus, P., Olek, K., Ottinger, H., Kozole, G., Belka, C., Meusers, P., Hense, J., Papadileris, Stefan, Pasternak, G., Pasternak, L., Karsten, U., Pecherstorfer, M., Zimmer-Roth, I., Poloskey, A., Petrasch, S., Kühnemund, O., Uppenkamp, M., Lütticken, R., Kosco, M., Schmitz, J., Petrides, Petro E., Dittmann, Klaus H., Krieger, O., Pflueger, K. -H., Grueber, A., Schoeneberger, J., Wenzel, E., Havemann, K., Pies, A., Kneba, M., Edel, G., Pohl, S., Bulgay-Mörschel, M., Polzin, R., Issing, W., Clemm, Ch., Schorn, K., Ponta, H., Zöller, M., Hofmann, M., Arch, R., Heider, K. -H., Rudy, W., Tölg, C., Herrlich, P., Prümmer, O., Scherbaum, W. A., Porzsolt, F., Prümmer, O., Krüger, A., Schrezenmeier, H., Schlander, H., Pineo, G., Marin, P., Gluckman, E., Shahidi, N. T., Bacigalupo, A., Ratajczak, M. Z., Gewirtz, A. M., Ratei, R., Borner, K., Bank, U., Bühling, F., Reisbach, G., Bartke, L., Kempkes, B., Kostka, G., Ellwart, X., Birner, A., Bornkamm, G. W., Ullrich, A., Dörmer, P., Henze, G., Parwaresch, R., Müller-Weihrich, S. T., Klingebiel, Th., Odenwald, E., Brandhorst, D., Tsuruo, T., Wetter, O., Renner, C., Pohl, C., Sahin, U., Renner, U., Zeller, K. -P., Repp, R., Valerius, Th., Sendler, A., Kalden, J. R., PIatzer, E., Reuss-Borst, M. A., Bühring, H. J., Reuter, C., der Landwehr, II, U. Auf, der Landwehr, II, U. Auf, Schleyer, E., Rolf, C., Ridwelski, K., Matthias, M., Preiss, R., Riewald, M., Puzo, A., Serke, S., Rohrer, B., Pfeiffer, D., Hepp, H., Romanowski, R., Schött, C., Rüther, U., Rothe, B., Pöllmann, H., Nunnensiek, C., Schöllhammer, T., Ulshöfer, Th., Bader, H., Jipp, P., Müller, H. A. G., Rupp, W., Lüthgens, M., Eisenberger, F., Afflerbach, C., Höller, A., Schwamborn, J. S., Daus, H., Krämer, K., Pees, H., Salat, C., Reinhardt, B., Düll, T., Knabe, H., Hiller, E., Sawinski, K., Schalhorn, A., Kühl, M., Heil, K., Schardt, Ch., Drexler, H. G., Scharf, R. E., Suhijar, D., del Zoppo, G. J., Ruggeri, Z. M., Roll, T., Möhler, T., Giselinger, H., Knäbl, P., Kyrie, P. A., Lazcíka, K., Lechner, X., Scheulen, M. E., Beelen, D. W., Reithmayer, H., Daniels, R., Weiherich, A., Quabeck, K., Schaefer, U. W., Reinhardt J., Grimm M., Unterhalt M., Schliesser, G., Lohmeyer, J., Schlingheider, O., von Eiff, M., Schulze, F., Oehme, C., van de Loo, J., Schlögl E., Bemhart M., Schmeiser, Th., Rozdzinski, E., Kern, W., Reichle, A., Moritz, T., Merk, Bruno, Schmid, R. M., Perkins, N. D., Duckett, C. S., Leung, K., Nabel, G. J., Pawlaczyk-Peter, B., Kellermann-Kegreiß, Schmidt E., Steiert, I., Schmidt-Wolf, G., Schmidt-Wolf, I. G. H., Schlegel, P., Blume, K. G., Chao, N. J., Lefterova, P., Laser, J., Schmitz, G., Rothe, G., Schönfeld, S., Schulz, S., Nyce, J. W., Graf, N., Ludwig, R., Steinhauser, I., Brommer, A. E., Qui, H., Schroeder, M., Grote-Kiehn, J., Bückner, U., Rüger, I., Schröder, J., Meusers, P., Weimar, Ch., Schoch, C., Schröter, G., Stern, H., Buchwald, B., Schick, K., Avril, N., Flierdt, E. v. d., Langhammer, H. R., Pabst, H. W., Alvarado, M., Witte, T., Vogt, H., Schuler, U., Brammer, K., Klann, R. C., Schumm, M., Hahn, J., Günther, W., Wullich, B., Moringlane, J. R., Schöndorf, S., Schwartz, S., Bühring, H. -J., Notter, M., Böttcher, S., Martin, M., Schmid, H., Lübbe, A. S., Leib-Mösch C., Wankmüller, H., Eilbrück, D., Funke, I., Cardoso, M., Duranceyk, H., Seitz, R., Rappe, N., Kraus, H., Egbring, R., Haasberg, M., Havemann, K., Seibach, J., Wollscheid, Ursula, Serke, St., Zimmermann, R., Shirai, T., Umeda, M., Anno, S., Kosuge, T., Katoh, M., Moro, S., Su, C. -Y., Shikoshi, K., Arai, N., Schwieder, G., Silling-Engelhardt, G., Zühlsdorf, M., Aguion-Freire-Innig, E., van de Loo, J., Stockdreher, K., Gatsch, L., Tischler, H. -J., Ringe, B., Diedrich, H., Franzi, A., Kruse, E., Lück, R., Trenn, G., Sykora, J., Wen, T., Fung-Leung, W. P., Mak, T. W., Brady, G., Loke, S., Cossman, J., Gascoyne, R., Mak, T., Urasinski, I., Zdziarska, B., Usnarska-Zubkiewicz, L., Kotlarek-Haus, S., Sciborskl, R., Nowosad, H., Kummer, G., Schleucher, N., Preusser, P., Niebel, W., Achterrath, W., Pott, D., Eigler, F. -W., Venook, A., Stagg, R., Frye, J., Gordon, R., Ring, E., Verschuer, U. v., Baur, F., Heit, W., Corrons, J. L. L. Vives, Vogel, M., Nekarda, H., Remy, W., Bissery, M. C., Aapro, M., Buchwald-Pospiech, A., Kaltwasser, J. P., Jacobi, V., de Vos, Sven, Asano, Yoshinobu, Voss, Harald, Knuth, Alexander, Wiedemann, G., Komischke, B., Horisberger, R., Wussow, P. v., Wanders, L., Senekowitsch, R., Strohmeyer, S., Emmerich, B., Selbach, J., Gutensohn, K., Wacker-Backhaus, G., Winkeimann, M., Send, W., Rösche, J., Weide, R., Parviz, B., Havemann, K., Weidmann, B., Henss, H., Engelhardt, R., Bernards, P., Zeidler, D., Jägerbauer, E., Colajori, E., Kerpel-Fronius, S., Weiss, A., Buchheidt, D., Döring, A., D.Saeger, H., Weissbach, L., Emmler, J., Wermes, R., Meusers, P., Flasshove, M., Skorzec, M., Käding, J., Platow, S., Winkler, Ute, Thorpe, Philip, Winter, S. F., Minna, J. D., Nestor, P. J., Johnson, B. E., Gazdar, A. F., Havemann, K., Carbone, D. P., Wit, M. de, Bittner, S., Hossfeld, D., Wittmann, G., Borchelt, M., Steinhagen-Thiessen, E., Koch, K., Brosch, T., Haas, N., Wölfel, C., Knuth, A., Wölfel, T., Safford, M., Könemann, S., Zurlutter, K., Schreiber, K., Piechotka, K., Drescher, M., Toepker, S., Terstappen, L. W. M. M., Bullerdiek, J., Jox, A., zur Hausen, H., Wolters, B., Stenzinger, W., Woźny, T., Sawiński, K., Kozłowska-Skrzypczak, M., Wussow, P. v., Hochhaus, T., Ansarl, H., Prümmer, O., Zapf, H., Thorban, S., Präuer, H., Zeller, W., Stieglitz, J. v., Dürken, M., Greenshaw, C., Kabisch, H., Reuther, C., Knabbe, C., Lippman, M., Havemann, K., Wellstein, A., Degos, L., Castaigne, S., Fenaux, P., Chomienne, C., Raza, A., Preisler, H. D., PEG Interventional Antimicrobial Strategy Study Group, Interventional Antimicrobial Strategy Study Group of the Paul Ehrlich Society (PEG), and H. Riehm for the BFM study group

Published
1992
Full Text
View/download PDF

16. Clinical relevance of protein C

Author

Pabinger, I.

Abstract

Protein C is, after activation by thrombin, a potent inhibitor of blood coagulation. An isolated deficiency of protein C increases the risk of thrombosis. The two forms of protein C deficiency, the heterozygous and the homozygous deficiency state, have different clinical features. Patients with heterozygous protein C deficiency are at a high risk to develop venous thrombosis and pulmonary embolism. In newborns with homozygous protein C deficiency with very low protein C levels (1%) a purpura fulminans like syndrome was observed. Heparin and coumarin derivatives are effective drugs in heterozygous protein C deficiency, homozygous patients may be treated either by replacement of protein C or coumarin derivatives. Decreased protein C levels were observed in various other diseases: Chronic and acute liver disease, disseminated intravascular coagulation, malignancy, postoperatively and during treatment with asparaginase. The role of protein C in these diseases to trigger thrombosis is not yet established.

Published
1986
Full Text
View/download PDF

17. Coumarin induced acral skin necrosis associated with hereditary protein C deficiency

Author

Pabinger, I., Karnik, R., Lechner, K., Slany, J., and Niessner, H.

Abstract

Hemorrhagic skin necrosis of the toes was observed in a patient with heterozygous protein C deficiency (protein C:Ag 32% and protein C activity 30%) on the 4th day of coumarin treatment overlapping with effective intravenous anticoagulation with heparin. Family studies revealed protein C deficiency in two sisters of the proposita without a history of thromboembolic disease. Immunologic studies in the proposita at the time of coumarin necrosis revealed slight depression of complement factor C4 and the presence of immune complexes. The present case and review of the literature show that the pathogenetic mechanism leading to coumarin necrosis in patients with protein C deficiency seems not yet to be fully understood.

Published
1986
Full Text
View/download PDF

18. Treatment patterns and bleeding outcomes in persons with severe hemophilia A and B in a real-world setting.

Author

Ay C, Perschy L, Rejtö J, Kaider A, and Pabinger I

Subjects
Adult, Austria epidemiology, Cohort Studies, Hemophilia A diagnosis, Hemophilia A epidemiology, Hemophilia B diagnosis, Hemophilia B epidemiology, Hemorrhage diagnosis, Hemorrhage epidemiology, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Factor IX administration & dosage, Factor VIII administration & dosage, Hemophilia A drug therapy, Hemophilia B drug therapy, Hemorrhage drug therapy, Severity of Illness Index
Abstract

The current standard of care treatment for severe hemophilia A and B (SHA and SHB) is the prophylactic intravenous replacement of coagulation factor VIII or IX (FVIII/FIX) to prevent spontaneous bleeding. Persons with hemophilia without prophylactic treatment receive therapy in case of bleeding, i.e., on demand. To assess treatment patterns, utilization of products, and bleeding outcomes in a real-world cohort of persons with SHA and SHB, defined as FVIII or FIX activity < 1%, data was retrospectively collected from hemophilia-specific patient diaries used for home treatment, medical records, and entries into the Austrian Hemophilia Registry from the year 2012 to 2017. Fifty-three male persons with SHA (n = 47) and SHB (n = 6) were included; 26 with SHA and 5 with SHB were on prophylaxis, 8 and 1 switched therapy regimen, and 13 and 0 received on-demand therapy. Persons on prophylaxis used a mean factor FVIII or FIX dose of 71.7 and 40.1 IU/kg/week. Median (IQR) annualized bleeding rates (ABR) in SHA were 28.0 (23.4-31.3) in the on-demand, 4.9 (1.6-13.5) in the prophylaxis group, and 3.0 (2.0-6.8) in the prophylactic group of SHB. Three persons with SHA had zero bleeds during the observation period. On-demand therapy and hepatitis B and C were associated with higher ABR but not age, weight, and HIV positivity. Bleeding rates and the proportion of on-demand therapy in persons with hemophilia were high in our real-world cohort. Further improvement is needed, which might be facilitated with the advent of factor products with extended half-life or non-factor therapies.

Published
2020
Full Text
View/download PDF

19. Low extracellular vesicle-associated tissue factor activity in patients with persistent lupus anticoagulant and a history of thrombosis.

Author

Hell L, Ay C, Posch F, Gebhart J, Koder S, Mackman N, Pabinger I, and Thaler J

Subjects
Adult, Female, Humans, Male, Middle Aged, Extracellular Vesicles metabolism, Lupus Coagulation Inhibitor blood, Venous Thrombosis blood
Abstract

Lupus anticoagulants (LA) are a heterogeneous group of antiphospholipid antibodies (aPLAs) that promote thrombosis. Tissue factor (TF)-bearing extracellular vesicles (EVs) might contribute to the prothrombotic state of patients with persistent LA and a history of thrombosis. To investigate if EV-associated TF activity is elevated in a well-defined group of LA-positive patients with a history of thrombosis in comparison to that of healthy controls. Adult patients (n = 94, median age 40.1 years, interquartile range (IQR) 29.9-53.4; 87% females) positive for LA and a history of thrombosis (78% venous thrombosis, 17% arterial thrombosis, 5% venous thrombosis and arterial thrombosis) and healthy age- and sex-matched controls (n = 30, median age 42.9 years, IQR 38.6-45.8, 77% females) were included in this study. EV-TF activity was determined with a factor Xa generation assay and anti-β2-glycoprotein (anti-β2GPI) and anticardiolipin (aCL) antibodies by enzyme-linked immunoassays. EV-TF activity did not differ between 94 LA-positive patients with a history of thrombosis (median 0.05 pg/mL, IQR 0.00-0.14) and 30 healthy controls (median 0.06, IQR 0.00-0.11, p = 0.7745). No correlation was found between EV-TF activity and lupus-sensitive activated partial thromboplastin time (aPTT-LA) (rho = 0.034), Rosner index (rho = - 0.056), anti-β2GPI IgG (rho = 0.05), anti-β2GPI IgM (rho = - 0.08), aCL IgG (rho = 0.12), and aCL IgM (rho = - 0.11) in LA-positive patients. We found low EV-TF activity levels in LA-positive patients and a history of thrombosis and no correlation with analyzed aPLAs. Our data indicate that circulating TF-bearing EVs do not contribute to the prothrombotic state of patients with LA.

Published
2019
Full Text
View/download PDF

20. Women with homozygous AT deficiency type II heparin-binding site (HBS) are at high risk of pregnancy loss and pregnancy complications.

Author

Kraft J, Sunder-Plassmann R, Mannhalter C, Quehenberger P, Tews G, Langer M, and Pabinger I

Subjects
Adolescent, Adult, Anticoagulants therapeutic use, Binding Sites genetics, Female, Heparin metabolism, Heparin therapeutic use, Homozygote, Humans, Infant, Newborn, Live Birth, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Pregnancy, Pregnancy Complications, Hematologic drug therapy, Premature Birth, Retrospective Studies, Risk Factors, Thrombophilia drug therapy, Young Adult, Abortion, Spontaneous genetics, Antithrombin III genetics, Mutation, Pregnancy Complications, Hematologic genetics, Thrombophilia genetics
Abstract

Data regarding outcome and therapy of pregnancies in patients with homozygous antithrombin (AT) deficiency are very rare. We conducted a retrospective, descriptive investigation with emphasis on the obstetric history of eight women with homozygous AT deficiency heparin-binding site (HBS), who had at least one pregnancy. The aim of the study was to get a better insight into the outcome and identify suitable management procedures of pregnancy in this rare disease. All patients suffered from homozygous AT deficiency caused by the mutation c.391C>T p.Leu131Phe in the AT gene (SERPINC1). The women reported in total 23 pregnancies; one pregnancy was excluded because of induced abortion. We found that only seven out of the 22 analyzed pregnancies ended with a live infant, all of them were born preterm. Among the 15 negative outcomes, seven were early pregnancy losses and eight were intrauterine fetal deaths. We found no clear association between treatment protocols and outcome. Eight pregnancies were not treated at all; all of them ended with pregnancy loss. We conclude that homozygous AT deficiency HBS, a form of severe thrombophilia, is associated with high risk of pregnancy loss and preterm delivery. Rigorous anticoagulation and/or replacement of AT during pregnancy may improve the outcome.

Published
2017
Full Text
View/download PDF

21. Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause.

Author

Gebhart J, Kepa S, Hofer S, Koder S, Kaider A, Wolberg AS, Haslacher H, Quehenberger P, Eigenbauer E, Panzer S, Mannhalter C, and Pabinger I

Subjects
Adult, Cohort Studies, Female, Humans, Male, Middle Aged, Blood Coagulation Disorders blood, Blood Coagulation Disorders diagnosis, Fibrinolysis physiology, Hemorrhage blood, Hemorrhage diagnosis
Abstract

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25-75 th percentile 32-58) with BUC and 98 healthy controls (65 females, median age 47 years, 25-75 th percentile 39-55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99-10.00) and 9.11 (7.17-13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80-22.58) and 17.03 (14.02-20.02), p < 0.001) and α2-antiplasmin (102 (94-109) and 98 (90-106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75-5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48-4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01-1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86-0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC., Competing Interests: Compliance with ethical standards Ethical approval All procedures performed in the study were in accordance with the ethical standards of the institutional research committee (ethikkommission.meduniwien.ac.at) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants before inclusion in the study. Funding CSL Behring supported the studies by an unrestricted grant and Stago provided the assays for the determination of TAFI, tPA-PAI-1 complexes, and D-dimer. Conflict of interests The authors declare that they have no competing interests.

Published
2017
Full Text
View/download PDF

22. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia.

Author

Janssens A, Rodeghiero F, Anderson D, Chong BH, Boda Z, Pabinger I, Červinek L, Terrell DR, Wang X, and Franklin J

Subjects
Adult, Aged, Bone Marrow metabolism, Cohort Studies, Collagen metabolism, Female, Humans, Male, Middle Aged, Platelet Count methods, Prospective Studies, Purpura, Thrombocytopenic, Idiopathic metabolism, Recombinant Fusion Proteins adverse effects, Reticulin metabolism, Thrombopoietin adverse effects, Treatment Outcome, Bone Marrow drug effects, Bone Marrow pathology, Purpura, Thrombocytopenic, Idiopathic drug therapy, Purpura, Thrombocytopenic, Idiopathic pathology, Receptors, Fc therapeutic use, Recombinant Fusion Proteins therapeutic use, Thrombopoietin therapeutic use
Abstract

The effects of romiplostim on bone marrow morphology were evaluated in adults with immune thrombocytopenia (ITP). Patients with platelet counts <50 × 10(9)/L, ≥1 prior ITP therapies, and no collagen at baseline received weekly subcutaneous romiplostim starting at 1 μg/kg, adjusted to maintain platelet counts between 50 and 200 × 10(9)/L. Biopsies were scheduled after 1, 2, or 3 years of romiplostim (cohorts 1, 2, and 3, respectively). Irrespective of scheduled time, biopsies were performed earlier if patients discontinued or failed to achieve/maintain a response to romiplostim. Reticulin (silver stain) and collagen (trichrome stain) were graded by two hematopathologists using the modified Bauermeister scale (0-4). Of 169 patients, 131 had evaluable biopsies; 9/131 (6.9 %) had increases of ≥2 grades on the modified Bauermeister scale (cohort 1: 0/34; cohort 2: 2/39; cohort 3: 7/58), including two with collagen. Three of the nine patients had follow-up biopsies, including one patient with collagen; changes were reversible after romiplostim discontinuation. Of the nine patients, one had neutropenia detected by laboratory test and two had adverse events of anemia, both non-serious and not treatment-related. By actual exposure (as some biopsies did not occur as scheduled), the number of patients with grade increases ≥2 were year 1: 3/41, year 2: 1/38, year 3: 5/52. Twenty-four patients sustained platelet counts ≥50 × 10(9)/L for ≥6 months with no ITP medications after discontinuing romiplostim, i.e., they entered clinical remission of their ITP. In conclusion, in patients with ITP receiving romiplostim, bone marrow changes were observed in a small proportion of patients.ClinicalTrials.gov identifier: NCT#00907478.

Published
2016
Full Text
View/download PDF

23. Anti-coagulation assessment with prothrombin time and anti-Xa assays in real-world patients on treatment with rivaroxaban.

Author

Königsbrügge O, Quehenberger P, Belik S, Weigel G, Seger C, Griesmacher A, Pabinger I, and Ay C

Subjects
Aged, Aged, 80 and over, Anticoagulants chemistry, Anticoagulants pharmacology, Factor Xa analysis, Female, Heparin chemistry, Heparin pharmacology, Humans, Male, Rivaroxaban, Atrial Fibrillation blood, Atrial Fibrillation prevention & control, Factor Xa metabolism, Factor Xa Inhibitors administration & dosage, Morpholines administration & dosage, Prothrombin Time, Stroke blood, Stroke prevention & control, Thiophenes administration & dosage
Abstract

Monitoring of anti-coagulation with the direct factor Xa inhibitor rivaroxaban is considered unnecessary in a routine clinical setting. However, assessment of its anti-coagulant effect may be desirable in certain clinical situations. We assessed prothrombin time (PT) reagents and commercially available anti-Xa assays (Biophen) calibrated for rivaroxaban and heparin in comparison to liquid chromatography-mass spectrometry (LC-MS/MS) measurements of rivaroxaban concentration in samples from patients on treatment with rivaroxaban for stroke prevention in atrial fibrillation. Citrate plasma samples were obtained from 30 randomly selected patients on uninterrupted treatment with rivaroxaban for a minimum of 1 month. The anti-Xa assays, direct Xa inhibitor (DiXa-I®), and Heparin LRT® were conducted for both wide and low calibrations for rivaroxaban. Measurements were compared to LC-MS/MS using correlation, linear regression, intra-class correlation, and Bland-Altman analysis. In 30 patients (9 female) of median age 71.5 years and BMI 26.5 kg/m(2), rivaroxaban concentrations between 2.4 and 625 ng/ml (median 82 ng/ml) were measured by LC-MS/MS. PT reagents were poorly correlated with rivaroxaban concentrations (r (2) = 0.52 and 0.09). Anti-Xa assays DiXa-I (r (2) = 0.95) and Heparin LRT (r (2) = 0.97) were correlated with rivaroxaban in all concentrations, but especially in low concentrations with low calibrations (r (2) = 0.97 and 0.98, respectively). The highest agreement occurred between Heparin LRT and low rivaroxaban concentrations with a mean difference of -5.3 ng/ml (limits of agreement, 12.9 to 2.4 ng/ml). Anti-Xa assays can indirectly determine the concentration of rivaroxaban for a wide range of concentrations in real-world patients. An interpretation of anti-Xa and PT measurements in treatment with rivaroxaban requires knowledge of the local reagents.

Published
2015
Full Text
View/download PDF

24. Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.).

Author

Kreher S, Ochsenreither S, Trappe RU, Pabinger I, Bergmann F, Petrides PE, Koschmieder S, Matzdorff A, Tiede A, Griesshammer M, and Riess H

Subjects
Anticoagulants administration & dosage, Anticoagulants adverse effects, Anticoagulants pharmacokinetics, Disease Susceptibility, Drug Interactions, Female, Hemorrhage chemically induced, Hemorrhage prevention & control, Heparin, Low-Molecular-Weight administration & dosage, Heparin, Low-Molecular-Weight adverse effects, Heparin, Low-Molecular-Weight therapeutic use, Humans, Hydroxyurea therapeutic use, Incidence, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative blood, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative complications, Male, Myeloproliferative Disorders blood, Myeloproliferative Disorders therapy, Phlebotomy, Platelet Aggregation Inhibitors administration & dosage, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors therapeutic use, Postoperative Complications prevention & control, Pregnancy, Pregnancy Complications, Hematologic drug therapy, Pregnancy Complications, Hematologic prevention & control, Preoperative Care, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Quinazolines therapeutic use, Secondary Prevention, Thrombophilia etiology, Venous Thromboembolism epidemiology, von Willebrand Diseases etiology, von Willebrand Diseases physiopathology, Anticoagulants therapeutic use, Myeloproliferative Disorders complications, Thrombophilia drug therapy, Venous Thromboembolism prevention & control
Abstract

Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial and venous thrombosis. Strategies of prevention may consist of platelet aggregation inhibitors and/or cytoreductive agents depending on the underlying disease and the individual risk. Clinical evidence for management of acute venous thromboembolic events in MPN patients is limited. Modality and duration of therapeutic anticoagulation after venous thrombosis has to be evaluated critically with special regard to the increased risk for spontaneous bleeding events associated with the underlying diseases. Both for therapy of the acute event and for secondary prophylaxis, low-molecular-weight heparins should preferentially be used. A prolongation of the therapeutic anticoagulation beyond the usual 3 to 6 months can only be recommended in high-risk settings and after careful evaluation of potential risks and benefits for the individual patient. New direct oral anticoagulants (NOAC) should not preferentially be used due to lack of clinical experience in patients with MPN and potential drug interactions (e.g. with JAK inhibitors). Consequent treatment of the underlying myeloproliferative disease and periodical evaluation of the response to therapy is crucial for optimal secondary prophylaxis of thromboembolic events in those patients.

Published
2014
Full Text
View/download PDF

25. Platelet activation and function during eltrombopag treatment in immune thrombocytopenia.

Author

Haselboeck J, Pabinger I, Ay C, Koder S, and Panzer S

Subjects
Adult, Aged, Blood Platelets physiology, Cell Aggregation physiology, Double-Blind Method, Female, Humans, Male, Middle Aged, Monocytes cytology, Monocytes physiology, P-Selectin metabolism, Placebos, Platelet Aggregation physiology, Benzoates pharmacology, Benzoates therapeutic use, Blood Platelets drug effects, Hydrazines pharmacology, Hydrazines therapeutic use, Platelet Activation drug effects, Pyrazoles pharmacology, Pyrazoles therapeutic use, Thrombocytopenia blood, Thrombocytopenia drug therapy, Thrombocytopenia immunology
Abstract

We monitored platelet activation by means of P-selectin and platelet monocyte aggregates (PMA) and platelet function by whole blood multiple electrode aggregometry and platelet adhesion under high shear in chronic immune thrombocytopenia patients to define changes in platelet activation during treatment with eltrombopag. Overall, platelet activation and function normalized with increasing platelet counts. However, P-selectin, which was already elevated before treatment, and PMA increased further transiently during the first weeks. The increases in P-selectin and in PMA indicate ongoing platelet activation during the early period of treatment.

Published
2012
Full Text
View/download PDF

26. Thrombin generation in patients with a bleeding tendency of unknown origin.

Author

Ay C, Haselböck J, Laczkovics C, Koder S, and Pabinger I

Subjects
Adult, Blood Coagulation Tests, Case-Control Studies, Clinical Laboratory Techniques, Female, Hemorrhage metabolism, Humans, Male, Middle Aged, Hemorrhage blood, Hemorrhage diagnosis, Hemorrhage etiology, Thrombin metabolism
Abstract

There are a number of persons with a mild to moderate bleeding tendency, in whom no underlying bleeding disorder can be detected despite thorough investigation of all known heritable and acquired haemostatic abnormalities. Thrombin is the central enzyme in the coagulation cascade, which is important for sufficient haemostasis. The measurement of an individual's potential to generate thrombin has been proposed for estimating the individual coagulation potential and predicting a hyper- or hypo-coagulable phenotype. The aim of our study was to investigate in vivo thrombin generation in a case-control study of patients with a bleeding tendency of unknown origin and in age- and sex-matched healthy individuals. Bleeding tendency was classified according to a standardized bleeding score. Thrombin generation was measured with a commercially available assay (Technothrombin-TGA, Technoclone, Vienna, Austria). In total, 101 patients (76 female; median age [25th-75th percentile], 44 [35-60] years) and 102 controls (67 women; median age, 47 [38-55] years) were enrolled. The distribution of parameters of thrombin generation among patients and controls showed no statistically significant difference: lag phase (14.4 [11.1-18.1] vs. 14.1 [12.1-17.1] min, p = 0.720), peak thrombin (179.8 [135.6-242.6] vs. 175.1 [143.1-261.4] nM, p = 0.576), time to peak thrombin (23.6 [18.1-28.6] vs. 22.6 [18.6-27.1] min, p = 0.790), velocity index (19.7 [13.0-39.0] vs. 22.6 [14.5-36.5] nM/min, p = 0.233) and area under the thrombin generation curve (3,491 [3,069-3,880] vs. 3,414 [3,045-3,750] nM thrombin, p = 0.673). In conclusion, the thrombin generation potential in patients with a bleeding tendency of unknown origin was not different from that of healthy individuals.

Published
2011
Full Text
View/download PDF

27. Long-term survival of patients with a history of venous thromboembolism.

Author

Reitter SE, Waldhoer T, Mayerhofer M, Eigenbauer E, Ay C, Kyrle PA, and Pabinger I

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Austria, Cohort Studies, Female, Follow-Up Studies, Hospitals, University, Humans, Male, Middle Aged, Outpatient Clinics, Hospital, Prognosis, Retrospective Studies, Sex Characteristics, Survival Analysis, Survival Rate, Venous Thromboembolism diagnosis, Venous Thromboembolism etiology, Young Adult, Venous Thromboembolism mortality
Abstract

Limited data are available regarding long-term survival following venous thromboembolism (VTE). The objectives of this study are to evaluate long-term survival by retrospective survival analysis in patients with a history of VTE and to compare their survival with that of the general population. Patients with a history of VTE (min. 3 months after VTE) without cancer, who were referred to our department between 1994 and 2007, were included in the analysis. Information concerning mortality was available through the Austrian Central Death Register. The survival of patients was compared with that of the age- and gender-matched general Austrian population. Three thousand two hundred-nine patients (mean age, 46.2; range, 14-89 years) were included. Median time interval between the first VTE and inclusion was 14 months; median observation period was 6.6 years. During the considered time period, 169 patients (5.3%) died. The cumulative survival in patients was 0.97 and 0.87 after 5 and 10 years; men had a higher death rate than women; patients with idiopathic VTE had a less favourable survival than those with a triggering event. When patients were compared to the general population, the cumulative relative survival was 1.02 (95% CI 1.00-1.03). In none of the analysed subgroups (different sites of VTE; idiopathic vs. secondary VTE) was a reduced cumulative relative survival found. The relative survival of male patients was even slightly better, whereas that of women equalled that of the normal population. Our results indicate that after the initial phase, VTE does not seem to impair long-term survival of patients with a history of VTE without cancer.

Published
2011
Full Text
View/download PDF

28. Circulating procoagulant microparticles in cancer patients.

Author

Thaler J, Ay C, Weinstabl H, Dunkler D, Simanek R, Vormittag R, Freyssinet JM, Zielinski C, and Pabinger I

Subjects
Aged, Cohort Studies, Female, Humans, Male, Middle Aged, Neoplasms complications, Prospective Studies, Risk Factors, Venous Thromboembolism etiology, Cell-Derived Microparticles metabolism, Coagulants blood, Neoplasms blood, Venous Thromboembolism blood
Abstract

Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vienna Cancer and Thrombosis Study. Study endpoint was the occurrence of symptomatic VTE. Sixty-five age- and sex-matched healthy controls were recruited for defining the cut-off point for elevated MPs (4.62 nanomolar phosphatidylserine [nM PS]), which was set at the 95th percentile of MP levels in healthy controls. The measurement of MPs was performed after capture onto immobilized annexin V, and determination of their procoagulant activity was quantified with a prothrombinase assay. During a median observation period of 710 days, 53 patients developed VTE. MP levels (nM PS) were significantly higher in cancer patients than in healthy controls (median [25th-75th percentile], 3.95 [1.74-7.96] vs. 1.19 [0.81-1.67], p<0.001). Multivariate analysis including age, sex, surgery, chemo- and radiotherapy showed no statistically significant association of the hazard ratio of elevated MPs with VTE (0.95 [95% CI, 0.55-1.64], p=0.856). In conclusion, MP levels were elevated in cancer patients compared to healthy individuals in this study. However, elevated MP levels were not predictive of VTE.

Published
2011
Full Text
View/download PDF

29. Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate.

Author

Stasi R, Newland A, Thornton P, and Pabinger I

Subjects
Adrenal Cortex Hormones therapeutic use, Azathioprine therapeutic use, Danazol therapeutic use, Humans, Receptors, Fc therapeutic use, Recombinant Fusion Proteins therapeutic use, Risk Assessment, Thrombopoietin therapeutic use, Time Factors, Purpura, Thrombocytopenic, Idiopathic drug therapy, Purpura, Thrombocytopenic, Idiopathic surgery, Splenectomy methods
Abstract

Patients with primary immune thrombocytopenia (ITP) may require treatment to reduce the risk of serious bleeding if platelets remain consistently below 30 × 10(9)/L. While approximately 70-80% of patients respond to an initial course of corticosteroids, relapse is common. For steroid-refractory patients, there is a choice between surgical splenectomy and further medical treatments, based on many factors including the patient's bleeding history, fitness for surgery, comorbidities, tolerance of adverse events, lifestyle and preferences. Treatments that have traditionally been used (corticosteroids, azathioprine, danazol) suppress the immune system, potentially predisposing patients to infection. Recent insights into the underlying pathophysiology of the disease have allowed the development of targeted therapies, including the thrombopoietin (TPO) receptor agonists, which enhance platelet production. Phase III trials have found romiplostim and eltrombopag to be well tolerated and effective in elevating platelet counts and reducing bleeding in both splenectomised and nonsplenectomised patients with chronic ITP. The B-cell targeted monoclonal antibody rituximab has also shown some potential in this setting, although data are currently limited and there are toxicity concerns. The decision whether to proceed to splenectomy or try other medical therapies in corticosteroid-refractory patients remains patient-specific. Splenectomy has its risks (including perioperative and long-term risks), and relapse/nonresponse are relatively common, but it offers the possibility of cure in the majority of patients. However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy.

Published
2010
Full Text
View/download PDF

30. Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate: a prospective clinical trial of emergency anticoagulation reversal.

Author

Pabinger I, Tiede A, Kalina U, Knaub S, Germann R, and Ostermann H

Subjects
Aged, Anticoagulants toxicity, Antidotes therapeutic use, Atrial Fibrillation etiology, Blood Coagulation Factors adverse effects, Blood Coagulation Factors pharmacokinetics, Blood Coagulation Factors therapeutic use, Coumarins toxicity, Drug Combinations, Drug-Related Side Effects and Adverse Reactions, Factor IX administration & dosage, Factor VII administration & dosage, Factor X administration & dosage, Female, Home Infusion Therapy standards, Humans, Male, Prothrombin administration & dosage, Time Factors, Treatment Outcome, Venous Thrombosis etiology, Blood Coagulation Factors administration & dosage, Emergency Medical Services, Home Infusion Therapy methods
Abstract

Prothrombin complex concentrate (PCC) infusion is preferred for emergency reversal of coumarin therapy. Rapid infusion can potentially save crucial time; however, the possible impact of high infusion speed on PCC safety and effectiveness has not been delineated. In a prospective multinational clinical trial with 43 patients receiving PCC (Beriplex P/N) for emergency reversal of coumarin therapy, infusion speeds were selected by the investigators. In a two-phase statistical analysis, the influence of baseline patient variables and dose on selected infusion speed was assessed. Then, the effect of infusion speed on reduction in international normalized ratio (INR) and on thrombogenicity marker pharmacokinetics was evaluated. Infusion speed ranged widely from 2.0 to 40.0 mL min(-1) with a median of 7.5 mL min(-1). Selection of infusion speed was not significantly influenced by gender, age, body mass index, presence of acute bleeding, indication for coumarin therapy, baseline INR, or PCC dose. Infusion speed was higher by a median of 2.2 mL min(-1) (95% confidence interval, 1.0-4.3 mL min(-1)) among patients receiving Beriplex P/N volumes > or =80 mL compared with smaller infusion volumes. Infusion speed did not affect INR attained 30 min following PCC infusion. None of the evaluated thrombogenicity marker pharmacokinetic parameters was affected by infusion speed. Infusions in one patient with questionable hemostatic efficacy and another with a possibly PCC-related thromboembolic event were at moderate and slow speeds, respectively. This study provides the first direct evidence that Beriplex P/N can be rapidly infused for emergency coumarin therapy reversal without altering safety or effectiveness.

Published
2010
Full Text
View/download PDF

31. Platelet glycoprotein Ibalpha polymorphisms and function evaluated by the platelet function analyzer PFA-100 in patients with lupus anticoagulant: the association with thromboembolic disease.

Author

Jilma-Stohlawetz P, Jilma B, Mannhalter C, Bencur P, Pabinger I, Vormittag R, Dunkler D, and Panzer S

Subjects
Adolescent, Adult, Aged, Collagen chemistry, Epinephrine chemistry, Female, Gene Frequency genetics, Humans, Lupus Coagulation Inhibitor genetics, Lupus Coagulation Inhibitor metabolism, Male, Middle Aged, Platelet Function Tests instrumentation, Platelet Function Tests methods, Platelet Glycoprotein GPIb-IX Complex metabolism, Retrospective Studies, Risk Factors, Shear Strength, Stress, Mechanical, Thromboembolism metabolism, Alleles, Platelet Glycoprotein GPIb-IX Complex genetics, Tandem Repeat Sequences genetics, Thromboembolism genetics
Abstract

Lupus anticoagulants (LA) are a surrogate marker for the risk of thromboembolic disease (TE). However, not all individuals with LA acquire TE, and it is desirable to distinguish those at risk for TE from those without. Platelets polymorphisms may contribute to the risk of TE, mainly those of glycoprotein (GP)Ibalpha: these are the variable number of tandem repeats (VNTR) and a dimorphism in the Kozak region, which affect platelet plug formation in healthy individuals under high shear stress rates. We determined polymorphisms within the GPIbalpha in individuals with persistent LA and a history of TE (LA/TE+) and in those without TE (LA/TE-). Further, we measured platelet function, as estimated by the collagen-epinephrine closure time (CEPI-CT) of the platelet function analyzer PFA-100 and compared all data with healthy controls. There was no difference of the VNTR alleles compared to healthy controls. The (-5)C allele of the Kozak dimorphism was significantly more frequent in LA patients compared to controls (p = 0.04), as a result of its increased frequency in LA/TE+ (vs controls p = 0.04), but there was no difference between LA/TE+ and LA/TE-. The increased frequency of the (-5)C allele resulted in an overrepresentation of (-5)TC genotype in the LA/TE+ group (p = 0.02) but not in a subgroup of 18 patients with arterial disease. The CEPI-CT of the PFA-100 was shorter in LA/TE+ than in LA/TE- (p = 0.044), but this difference did not persist after exclusion of patients with low platelet counts or low ristocetin cofactor activity. Unlike in healthy individuals, the CEPI-CT was not related to any Kozak dimorphism, neither in LA/TE-, nor in LA/TE+. Thus, the Kozak dimorphism may just contribute to stronger factors disposing individuals with LA towards TE without any discernible effect on their in vitro platelet function estimated by the PFA-100.

Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results