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1. Contributors

Author

Omar Abdel-Wahab, Janet L. Abrahm, Sharon Adams, Adeboye H. Adewoye, Carl Allen, Richard F. Ambinder, Claudio Anasetti, John Anastasi, Julia A. Anderson, Joseph H. Antin, Aśok C. Antony, David J. Araten, Philippe Armand, Gillian Armstrong, Scott A. Armstrong, Donald M. Arnold, Andrew S. Artz, Farrukh T. Awan, Trevor P. Baglin, Don M. Benson, Edward J. Benz, Nancy Berliner, Govind Bhagat, Nina Bhardwaj, Ravi Bhatia, Smita Bhatia, Mihir D. Bhatt, Vijaya Raj Bhatt, Menachem Bitan, Craig D. Blinderman, Catherine M. Bollard, Benjamin S. Braun, Malcolm K. Brenner, Gary M. Brittenham, Robert A. Brodsky, Myles Brown, Hal E. Broxmeyer, Kathleen Brummel-Ziedins, Andrew M. Brunner, Francis K. Buadi, Birgit Burkhardt, Melissa Burns, John C. Byrd, Paolo F. Caimi, Michael A. Caligiuri, Michelle Canavan, Alan B. Cantor, Manuel Carcao, Michael C. Carroll, Shannon A. Carty, Jorge J. Castillo, Anthony K.C. Chan, John Chapin, April Chiu, John P. Chute, David B. Clark, Thomas D. Coates, Christopher R. Cogle, Nathan T. Connell, Elizabeth Cooke, Sarah Cooley, Paolo Corradini, Mark A. Creager, Richard J. Creger, Caroline Cromwell, Mark A. Crowther, Melissa M. Cushing, Corey Cutler, Chi V. Dang, Nika N. Danial, Sandeep S. Dave, James A. DeCaprio, Mary C. Dinauer, Shira Dinner, Reyhan Diz-Küçükkaya, Roger Y. Dodd, Michele L. Donato, Kenneth Dorshkind, Gianpietro Dotti, Yigal Dror, Kieron Dunleavy, Christopher C. Dvorak, Benjamin L. Ebert, Michael J. Eck, John W. Eikelboom, Narendranath Epperla, William B. Ershler, William E. Evans, Stefan Faderl, James L.M. Ferrara, Alexandra Hult Filipovich, Martin Fischer, James C. Fredenburgh, Kenneth D. Friedman, Ephraim Fuchs, Stephen J. Fuller, David Gailani, Jacques Galipeau, Patrick G. Gallagher, Karthik A. Ganapathi, Lawrence B. Gardner, Adrian P. Gee, Stanton L. Gerson, Morie A. Gertz, Patricia J. Giardina, Christopher J. Gibson, Karin Golan, Todd R. Golub, Matthew J. Gonzales, Jason Gotlib, Stephen Gottschalk, Marianne A. Grant, Timothy A. Graubert, Xylina T. Gregg, John G. Gribben, Dawn M. Gross, Tanja A. Gruber, Joan Guitart, Sandeep Gurbuxani, Shiri Gur-Cohen, Alejandro Gutierrez, Mehdi Hamadani, Parameswaran N. Hari, John H. Hartwig, Suzanne R. Hayman, Catherine P.M. Hayward, Robert P. Hebbel, Helen E. Heslop, Christopher Hillis, Christopher D. Hillyer, Karin Ho, David M. Hockenbery, Ronald Hoffman, Kerstin E. Hogg, Shernan G. Holtan, Hans-Peter Horny, Yen-Michael S. Hsu, Zachary R. Hunter, James A. Huntington, Camelia Iancu-Rubin, Ali Iqbal, David E. Isenman, Sara J. Israels, Joseph E. Italiano, Elaine S. Jaffe, Iqbal H. Jaffer, Sundar Jagannath, Ulrich Jäger, Nitin Jain, Paula James, Sima Jeha, Michael B. Jordan, Cassandra D. Josephson, Moonjung Jung, Leo Kager, Taku Kambayashi, Jennifer A. Kanakry, Hagop M. Kantarjian, Jason Kaplan, Matthew S. Karafin, Aly Karsan, Randal J. Kaufman, Richard M. Kaufman, Frank G. Keller, Kara M. Kelly, Craig M. Kessler, Nigel S. Key, Alla Keyzner, Alexander G. Khandoga, Arati Khanna-Gupta, Eman Khatib-Massalha, Harvey G. Klein, Birgit Knoechel, Orit Kollet, Barbara A. Konkle, Dimitrios P. Kontoyiannis, John Koreth, Gary A. Koretzky, Dipak Kotecha, Marina Kremyanskaya, Anju Kumari, Timothy M. Kuzel, Ralf Küppers, Martha Q. Lacy, Elana Ladas, Wendy Landier, Kfir Lapid, Tsvee Lapidot, Peter J. Larson, Marcel Levi, Russell E. Lewis, Howard A. Liebman, David Lillicrap, Wendy Lim, Judith C. Lin, Robert Lindblad, Gregory Y.H. Lip, Jane A. Little, Jens G. Lohr, José A. López, Francis W. Luscinskas, Jaroslaw P. Maciejewski, Navneet S. Majhail, Olivier Manches, Robert J. Mandle, Kenneth G. Mann, Catherine S. Manno, Andrea N. Marcogliese, Guglielmo Mariani, Francesco M. Marincola, John Mascarenhas, Steffen Massberg, Rodger P. McEver, Emer McGrath, Matthew S. McKinney, Rohtesh S. Mehta, William C. Mentzer, Giampaolo Merlini, Reid Merryman, Marc Michel, Anna Rita Migliaccio, Jeffrey S. Miller, Martha P. Mims, Traci Heath Mondoro, Paul Moorehead, Luciana R. Muniz, Nikhil C. Munshi, Vesna Najfeld, Lalitha Nayak, Ishac Nazy, Anne T. Neff, Paul M. Ness, Luigi D. Notarangelo, Sarah H. O'Brien, Owen A. O'Connor, Martin O'Donnell, Amanda Olson, Stuart H. Orkin, Menaka Pai, Sung-Yun Pai, Michael Paidas, Sandhya R. Panch, Reena L. Pande, Thalia Papayannopoulou, Rahul Parikh, Effie W. Petersdorf, Shane E. Peterson, Stefania Pittaluga, Doris M. Ponce, Laura Popolo, Josef T. Prchal, Ching-Hon Pui, Pere Puigserver, Janusz Rak, Carlos A. Ramos, Jacob H. Rand, Margaret L. Rand, Dinesh S. Rao, Farhad Ravandi, David J. Rawlings, Pavan Reddy, Mark T. Reding, Andreas Reiter, Lawrence Rice, Matthew J. Riese, Arthur Kim Ritchey, David J. Roberts, Elizabeth Roman, Cliona M. Rooney, Steven T. Rosen, David S. Rosenthal, Marlies P. Rossmann, Antal Rot, Scott D. Rowley, Jeffrey E. Rubnitz, Natalia Rydz, Mohamed E. Salama, Steven Sauk, Yogen Saunthararajah, William Savage, David Scadden, Kristen G. Schaefer, Fred Schiffman, Robert Schneidewend, Stanley L. Schrier, Edward H. Schuchman, Bridget Fowler Scullion, Kathy J. Selvaggi, Keitaro Senoo, Montaser Shaheen, Beth H. Shaz, Samuel A. Shelburne, Elizabeth J. Shpall, Susan B. Shurin, Deborah Siegal, Leslie E. Silberstein, Lev Silberstein, Roy L. Silverstein, Steven R. Sloan, Franklin O. Smith, James W. Smith, Katy Smith, David P. Steensma, Martin H. Steinberg, Wendy Stock, Jill R. Storry, Susan L. Stramer, Ronald G. Strauss, David F. Stroncek, Justin Taylor, Swapna Thota, Steven P. Treon, Anil Tulpule, Roberto Ferro Valdes, Peter Valent, Suresh Vedantham, Gregory M. Vercellotti, Michael R. Verneris, Elliott P. Vichinsky, Ulrich H. von Andrian, Julie M. Vose, Andrew J. Wagner, Ena Wang, Jia-huai Wang, Theodore E. Warkentin, Melissa P. Wasserstein, Ann Webster, Daniel J. Weisdorf, Jeffrey I. Weitz, Connie M. Westhoff, Allison P. Wheeler, Page Widick, James S. Wiley, Basem M. William, David A. Williams, Wyndham H. Wilson, Joanne Wolfe, Lucia R. Wolgast, Deborah Wood, Jennifer Wu, Joachim Yahalom, Donald L. Yee, Anas Younes, Neal S. Young, and Michelle P. Zeller

Published
2018
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3. Procoagulant Platelet Subpopulation Formation in Whole Blood: Correlation with Whole Blood Clotting Time and 5-Year Mean Bleeding Score in Individuals with Factor VIII Deficiency

Author

Aimee K. Paradis, Georges E. Rivard, Kathleen Brummel Ziedins, and Beth A. Bouchard

Subjects
medicine.medical_specialty, biology, business.industry, Immunology, Factor V, Cell Biology, Hematology, Biochemistry, Endocrinology, Prothrombinase, Internal medicine, Hemostasis, biology.protein, medicine, Platelet, Platelet activation, Mean platelet volume, business, Factor IX, medicine.drug, Whole blood
Abstract

Abstract 4022 Poster Board III-958 Different clinical phenotypes are often observed among individuals with hemorrhagic or thrombotic disorders despite the presence of the same mutation and/or factor levels suggesting that additional genetic and/or environmental factors influence clinical presentation. As thrombin plays a central role in hemostasis, factors that affect an individual's ability to generate thrombin may lead to an increased risk of hemorrhage or thrombosis. The goal of this study was to assess procoagulant platelet formation in individuals with hemophilia A using a rapid, whole blood flow cytometric assay of prothrombinase complex assembly on platelets described previously. In this assay, Ca2+-dependent factor Xa binding to activated platelets is used as a marker of thrombin generating potential as it has been shown previously to correlate with platelet prothrombinase activity in a washed platelet system. Procoagulant platelet subpopulation formation in 15 men with varying degrees of factor VIII-deficiency was evaluated and compared to two independent measures of hemostatic competence: a 5-year mean bleeding score and whole blood clot time. In these individuals, the % activated platelets binding factor Xa in whole blood varied from 2.35 – 9.0% (n = 30), which is consistent with what is observed in unaffected individuals (1.5 – 41.5%, n = 136). Bleeding was scored independently by two experienced hemophilia nurses and one hematologist at Centre Hospitalier Universitaire Sainte Justine based on each individual's bleeding history, including hemarthroses, soft tissue hematoma, and annual factor VIII usage, and averaged. The 5-year mean bleeding scores in these individuals ranged from 0 – 20.4. Linear regression analyses indicated that in this population the % activated platelets binding factor Xa correlated indirectly with the 5-year mean bleeding score, where individuals with lower bleeding scores (i.e. less bleeding episodes and/or factor VIII usage) generated larger procoagulant platelet subpopulations. The time to clot formation in a tissue factor-dependent, contact pathway-suppressed whole blood clotting assay described previously, was also determined. The clot time, which was determined visually, and ranged from ∼3 – 7 min, also correlated indirectly, though less well, with the % activated platelets binding factor Xa in whole blood (r = -0.23). Thus, consistent with what was observed with the bleeding score, those individuals who clotted more quickly (i.e. exhibited a greater degree of hemostatic competence) generated more proacoagulant platelets. Platelet procoagulant subpopulation formation was also compared to other hematological measures. An inverse correlation was observed between the % activated platelets binding factor Xa and mean platelet volume (r = -0.347), suggesting that in this population, individuals with smaller platelets (i.e. platelets with fewer prothrombinase binding sites) may generate a greater number of platelets capable of assembling prothrombinase. In contrast, no correlation was observed between whole blood platelet number and % activated platelets binding factor Xa. Interestingly, factor Xa binding was also negatively correlated with plasma levels of factor IX (r = -0.56) and factor V (r = -0.62). Platelet subpopulation formation was also weakly and negatively associated with the aPTT (r = - 0.28). In this small population of individuals with hemophilia A, whole blood platelet factor Xa binding correlates with bleeding phenotype. These observations support the notion that this measurement can be used to predict an individuals propensity to bleed or clot. Disclosures: No relevant conflicts of interest to declare.

Published
2009
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