Richard H. Aster, M.D.
Richard H. Aster, M.D. Senior Investigator
Blood Research Institute
BloodCenter of Wisconsin Professor
Departments of Medicine and Pathology
Medical College of Wisconsin Postdoctoral Training
Massachusetts General Hospital
National Institutes of Health
Thorndike Laboratory, Harvard Medical School
Doctoral Training M.D., University of Michigan, 1957
Selected Publications
Grant Support
Invited Lectures
Patents
Laboratory Staff
Contact Information Research Interests
Immune Disorders of the Blood Blood cells are targeted for destruction by antibodies in many clinically important disorders. Some of these conditions have an autoimmune etiology; others are caused by alloantibodies, isoantibodies or drug sensitivity. We are engaged in studies to improve the understanding of this family of disorders. Areas of current research interest are the drug-immune cytopenias, neonatal alloimmune thrombocytopenia and immune disorders that affect neutrophils. Current studies are aimed at characterizing the basis for the aberrant immune response that leads to these conditions, mechanism(s) by which drugs promote binding of drug-induced antibodies to their targets and molecular characteristics of antigens recognized by pathogenic antibodies. We expect these studies will lead to improved methods to diagnose, treat and prevent hematologic diseases associated with autoimmunity, alloimmunity and drug sensitivity. Selected Publications - Bougie DW, Wilker PR, Wuitschick ED, Curtis BR, Malik M, LaVine S, Lind RN, Pereira J, Aster RH: Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa. Blood 100: 2071-6, 2002
- Peterson JA, Nyree CE, Newman PJ, Aster RH: A site involving the "hybrid" and PSI homology domains of GPIIIa (beta 3 integrin subunit) is a common target for antibodies associated with quinine-induced immune thrombocytopenia. Blood 101: 937-942, 2003
- Curtis BR, Divgi A, Garritty M, Aster RH. Delayed thrombocytopenia after treatment with abciximab: A distinct clinical entity associated with the immune response to the drug. J Thromb Haemost, 2:985-992, 2004
- Davoren A, Saving K, McFarland JG, Aster RH, Curtis BR. Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion 44:1041-46, 2004
- Aster RH. Drug-induced immune cytopenias. Toxicology; 209: 149-153, 2005
- Liu CY, Battaglia M, Lee, SH, Sun QH, Aster RH, Visentin GP. Platelet factor 4 (PF4) differentially modulates CD4+CD25+ (regulatory) vs. CD4+CD25+. J immunol, 174: 2680-2686, 2005
- Peterson JA, Balthazor SM, Curtis BR, McFarland JG, Aster RH. Maternal alloimmunization against the rare platelet-specific antigen Maxa (HPA-9b) is an important cause of neonatal alloimmune thrombocytopenia. Transfusion. 45:1487-95, 2005
- Curtis BR, Reno R, Aster RH. Neonatal Alloimmune Neutropenia Due to Maternal IgG Antibodies Against the Neutrophil Alloantigen HNA-1c (SH): A report of 5 cases. Transfusion 45:1308-1313, 2005
- Curtis BR, Aster RH, Cooling LL. Expression of ABH antigens on platelets. Blood 107:842-93, 2006
- Curtis BR, Aster RH. ABH antigens on platelets. Blood 107:842-3, 2006
- Bougie DW, Wilker P, Aster RH. Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies. Blood 108:922-927, 2006
- Von Drygalski A, Curtis BR, Bougie DW, McFarland JG, Ahl S, Limbu I, Baker KR, Aster RH. Immune thrombocytopenia in patients treated with vancomycin. New Engl J Med 356: 904-910, 2007
- Aster RH and Bougie DW. Current Concepts: Drug-induced immune thrombocytopenia. N Engl J Med 357: 580-587, 2007
- Bougie, DW, Benito AI, Sanchez-Albarca, LI, Torres, R, Birenbaum J, Aster RH. Immune thrombocytopenia induced by a metabolite of acetaminophen. Blood 109: 3609-3610, 2007
- Newman PJ, Aster RH, Boylan B. Human platelets circulating in mice: applications for interrogating platelet function and survival, the efficacy of antiplatelet therapeutics, and the molecular basis of platelet immunological disorders. J Thromb Haemost. 5 (Suppl 1) 305-309, 2007
- Warkentin TE, Maurer BT, Aster RH. Heparin-Induced Thrombocytopenia, Bilateral Adrenal Necrosis, and Deep-Vein Thrombosis Associated with Fondaparinux Thromboprophylaxis. N Engl J Med; 356: 2653-55, 2007
- Visentin GP, Liu CY, Aster RH: Molecular immunopathogenesis of heparin-induced thrombocytopenia (HIT). In Heparin-Induced Thrombocytopenia and Thrombosis., 3rd Ed, TW Warkentin et al. eds Marcel-Dekker Inc, NY, 2007
- Curtis BR, Fick A, Lochowicz AJ, McFarland JG, Ball RH, Peterson J, Aster RH. Neonatal Alloimmune Thrombocytopenia (NAIT) Associated with Maternal-Fetal Incompatibility for Blood Group B. Transfusion, 48: 358-364, 2008
- Peterson JA, Nelson T, Aster RH. Fine specificity of drug-dependent antibodies reactive with a restricted domain of GPIIIa. Blood, 111: 1234-1239, 2008
- Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH. Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 113:1105-1111, 2009
- Gao C, Boylan B, Bougie D, Gill JC, Birenbaum J, Newman DK, Aster RH, Newman PJ. Eptiifbatide-induced thrombocytopenia and thrombosis in humans require FcgammaRIIa and the integrin beta3 cytoplasmic domain. J Clin Invest 119(3):504-11, 2009
- Rousan TA, Aldoss IT, Cowley BD Jr, Curtis BR, Bougie DW, Aster RH George JN. Recurrent acute thrombocytopenia in the hospitalized patients: sepsis, DIC, HIT, or antibiotic-induced thrombocytopenia. Am J Hematol 85(1):71-4, 2010
- Curtis BR, Cox NJ, Sullivan MJ, Konkashbaey A, Bowens K, Hansen K, Aster RH. The neutrophil alloantigen HN-3a (5b) is located on choline transporter-like protein 2 (CTL2) and appears to be encoded by an R>Q154 amino acid substitution. Blood 115(10):2073-6, 2010
- Peterson JA, Gitter, ML, Kanak A, Curtis BR, McFarland JG, Bougie D, Aster, RH. New low frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion, 50:324-333, 2010
- Curtis BR, Sullivan MJ, Holyst MT, Szabo A, Bougie DW, Aster RH. HNA-3a-specific antibodies recognize choline transporter-like protein-2 peptides containing arginine, but not glutamine at Position 154. Transfusion 51(10):2168-74, 2011
- Kowalska MA, Krishnaswamy S, Rauova L, Zhai L, Hayes V, Amirikian K, Esko JD, Bougie DW, Aster RH, Cines DB, Poncz M. Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT. Blood 118(10):2882-8, 2011
- Kanack A, Peterson JA, Sullivan MJ, Bougie DW, Curtis BR, Aster RH Full length, recombinant choline transporter-like protein 2 (CTL2) containing arginine 154 reconstitutes the epitope recognized by HNA-3a antibodies whenexpressed in HEK293 cell, Transfusion, In Press, 2012
- Peterson JA, Pechauer S, Gitter ML, Kanack A, Curtis BR, Reese J, Kamath VM, McFarland JG, Aster RH, New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia, Transfusion, In Press, 2012
- Achterbergh A, Vermeer E, Porcelijn L, Deenik W, Daemen-Gubbels K, Bowens Aster RH, Curtis BR, Immune Thrombocytopenia Associated with Consumption of English Walnuts, Lancet, In Press, 2012
Grant Support - Grant: R01HL013629 "Hemorrhagic Diseases" - National Heart Lung and Blood Institute, (Principal Investigator) 1970-2012
- Grant: R21HL106286 "Prevalence and immunogenicity of HNA-3a and -3b antibodies and antigens" - NHLBI (Principal Investigator) 2011-2012
Invited Lectures - June 16, 2006 “Immune thrombocytopenia induced by GPIIb/IIIa inhibitors”. 9th Internaitonal Symposium on Platelet and Neutrophil Immunology, Tromso, Norway
- October 7, 2006 “Drug-induced immune thrombocytopenia – An update.” Midwest Platelet Meeting, U of Illinois Chicago, Chicago IL.
- July 6, 2007 “Sensitivity and specificity of lab testing for drug-induced immune thrombocytopenia: Quinine and vancomycin as models.” Workshop on Platelet Immunology, Scientific Subcommittee (SSC) meeting, International Society of Thrombosis and Haemostasis, Geneva, Switzerland
- July 6, 2007 “Delayed-onset HIT: musings on pathogenesis.” Workshop on Platelet Immunology, Scientific Subcommittee (SSC) meeting, International Society of Thrombosis and Haemostasis, Geneva, Switzerland
- April 25, 2008, Drug-induced immune thrombocytopenia – An under-diagnosed group of disorders. Medical Grand Rounds, St Mary’s Medical Center, Chicago IL
- May 15, 2008, Drug-induced immune thrombocytopenia – new observations on pathogenesis. Ninth European Congress of Platelet and Neutrophil Immunology, Thun, Switzerland
- July 3, 2008, Drug-induced Immune Thrombocytopenia: Molecular Mechanisms. Gordon Conference on Hemostasis. Waterville Valley, NH
- July 10, 2009. Drug-induced immune thrombocytopenias: New concepts of pathogenesis. International Society Thrombosis and Haemostasis. Boston
- October 26, 27, 2009 “New approaches to detection of platelet-reactive antibodies.” AABB, New Orleans
Patents - Method of detecting heparin-induced thrombocytopenia. US Patent 5,972,718 Issued October 26, 1999
- Method and kit for detecting heparin-induced thrombocytopenia. US Patent 5,972,717 Issued October 26, 1999
- Nucleic acids for the detection of the Bak polymorphism in human platelet membrane glycoprotein IIb US Patent 5,652,357 Issued July 19, 1997
- Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof 5,091,302 Issued February 25, 1992; US Patent 5,391,714 Patent Issued February 21, 1995; US Patent 5,670,337 Issued September 23, 1997; Japanese Patent 3,221,679 Issued August 17, 2001
- Typing for the alloantigen HPA-3a (5b) and detection of HPA-3a-specific antibodies. Pending.
Laboratory Staff Platelet Immunology Group Employment Opportunities If opportunities are available, they will be listed on the Employment page.
Contact Information
Phone: (414) 937-6338 Fax: (414) 937-6284 E-Mail:
richard.aster@bcw.edu
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