Willy A. Flegel, MD

MD, University of Frankfurt/Germany
Privatdozent, University of Ulm/Germany

Dr. Flegel earned his medical degree and received a Doctor of Medicine by research (Dr. med., magna cum laude) at the University of Frankfurt, trained in transfusion medicine at the University of Ulm and performed post-doctoral research at University of California at San Diego.

He was appointed head of the Immunohematology Department at the German Red Cross Blood Center in Ulm and member of the Medical Faculty, University of Ulm, as Professor (full/apl. Professor). He is Visiting Professor, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China since 2014 and Professor (adjunct), Georgetown University Medical Center, Washington DC since 2015.

Dr. Flegel has been actively involved in blood transfusion medicine since 1986 and at the forefront of research on Rh antigens since 1994. His professional activities include founding and coordinating the German Rare Donor Program 1999 – 2009; serving as a member of the International Society of Blood Transfusion (ISBT) Working Parties for Rare Donors 2000 – 2010, on Red Cell Immunogenetics and Blood Group Terminology since 2004 and on Immunohematology since 2014; inventing for patents in the field of molecular immunohematology; and organizing the oldest and largest external quality assessment (EQA) scheme for molecular immunohematology proficiency in an effort to enhance patient safety internationally.

He serves as Associate Editor of Transfusion, Senior Editor of Journal of Translational Medicine and on the editorial boards of Blood Transfusion and Chinese Medical Journal. He has published more than 175 articles in scientific journals, authored a medical-legal text book on transfusion medicine and has written several book chapters.

Dr. Flegel came to the NIH Clinical Center Department of Transfusion Medicine (DTM) in 2009 as Chief, Laboratory Services Section. In this role, he directs the Transfusion Services (TSL) and HLA Laboratories. During his tenure, the TSL expanded genotyping for red cell antigens and the HLA laboratory established KIR gene assays, including next generation sequencing technologies.

Research interests include blood group genotyping; relationship of genotype, phenotype and function of blood group proteins; stem cell surface antigens in vivo and during ex vivo expansion; and immunogenetics in hematopoietic stem cell transplantation.

• NIH Clinical Center CEO Award, 2017 (Strategic Initiative)
• NIH Clinical Center Director's Award, 2015 (Patient Care)
• NIH Clinical Center Director's Award, 2012 (Patient Care)
• NIH Clinical Center Director's Award, 2010 (Strategic Initiative)
• Honorary Member of the Swiss Association for Transfusion Medicine, 2005
• Philip Levine Award of the German Society for Transfusion Medicine and Immunohematology, 2004.

Book

Lippert H-D, Flegel WA. Kommentar zum Transfusionsgesetz (TFG) und den Hämotherapie-Richtlinien. XXXIX, 521 pages. Springer, Berlin 2002

Book Chapters

Flegel WA, Wagner FF. Blutgruppen: Alloantigene auf Erythrozyten. In: Kiefel V (Ed.) Transfusionsmedizin und Immunhamatologie. Springer, Berlin 2010, 4th edition

Flegel WA. Transfusion. In: Delves PJ, Roitt IM (Eds.) Encyclopedia of Immunology. Academic Press, London 1999, 2nd edition

Journal Reviews and Editorials

Flegel WA, Chen Q, Castilho L, Keller MA, Klapper EB, Lane WJ, Pirenne F, Stack G, St-Louis M, Tormey CA, Waxman DA, Weinstock C, Wendel S, Denomme GA. Molecular immunohaematology round table discussions at the AABB Annual Meeting, Orlando 2016. Blood Transfus 2018: in press.

Flegel WA, Peyrard T, Chiaroni J, Tournamille C, Jamet D, Pirenne F. A proposal for a rational transfusion strategy in patients of European and North African descent with weak D type 4.0 and 4.1 phenotypes. Blood Transfus 2018: in press.

Denomme GA, Anani WQ, Avent ND, Bein G, Briggs LB, Lapadat RC, Montemayor C, Rios M, St-Louis M, Uhl L, Wendel S, Flegel WA. Red cell genotyping precision medicine: a conference summary. Ther Adv Hematol 2017;8: 277-91.

Sandler SG, Chen LN, Flegel WA. Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RHD genotype. Br J Haematol 2017;179: 10-9.

Flegel WA. Red cell alloimmunisation: incidence and prevention. Lancet Haematology 3: e260 – e261, 2016

Klein HG, Flegel WA, Natanson C. Red blood cell transfusion: precision vs imprecision medicine. JAMA 314: 1557 – 1558, 2015

Flegel WA, Natanson C, Klein HG. Does prolonged storage of red blood cells cause harm? Br J Haematol 165: 3 – 16, 2014

Flegel WA, Roseff SD, Tholpady A. Phasing-in RHD genotyping. Arch Path Clin Lab 138: 585 – 588, 2014

Flegel WA, Johnson ST, Keller MA, Klapper EB, Khuu HM, Moulds JM, Seltsam AW, Stack G, St-Louis M, Tormey CA, Wagner FF, Weinstock C, Yazer MH, Denomme GA. Molecular immunohematology round table discussions at the AABB Annual Meeting, Boston 2012. Blood Transfusion 12: 280 – 286, 2014

Flegel WA. Molecular genetics and clinical applications for RH. Transf Apher Sci 44, 81 – 91, 2011

Flegel WA. Immunogenicity reloaded. Blood 114, 3979 – 3980, 2009

Denomme GA, Flegel WA. Applying molecular immunohematology discoveries to standards of practice in blood banks: now is the time. Transfusion 48, 2461 – 2475, 2008

Flegel WA. Will MICA glitter for recipients of kidney transplants? N Engl J Med 357, 1337 - 1339, 2007

Flegel WA. Homing in on D antigen immunogenicity. Transfusion 45, 466 – 468, 2005

Northoff H, Flegel WA. Genotyping and phenotyping: the two sides of one coin. Infusionsther Transfusionsmed 26, 5, 1999

Journal Articles

Yin Q, Srivastava K, Gebremedhin A, Makuria AT, Flegel WA. Long-range haplotype analysis of the malaria parasite receptor gene ACKR1 in an East-African population. Human Genome Variation 2018;5: 26.

Charles BA, Hsieh MM, Adeyemo AA, Shriner D, Ramos E, Chin K, Srivastava K, Zakai NA, Cushman M, McClure LA, Howard V, Flegel WA, Rotimi CN, Rodgers GP. Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia. PLoS One 2018;13: e0194400.

Ou GJ, Su PC, Yu H, Ji X, Liu F, Wang SL, Kong YJ, Li L, Wang J, Liu Z, Flegel WA. HNA-3a and HNA-3b antigens among 9 ethnic populations and the Han population in Southwest China. J Transl Med 2018;16: 67.

Ouchari M, Srivastava K, Romdhane H, Jemni Yacoub S, Flegel WA. Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia. Transfusion 2018;58: 306-12.

Srivastava K, Stiles DA, Wagner FF, Flegel WA. Two large deletions extending beyond either end of the RHD gene and their red cell phenotypes. J Human Genetics 63: 27 – 35, 2018

Allen ES, Srivastava K, Hsieh MM, Fitzhugh CD, Klein HG, Tisdale JF, Flegel WA. Immunohematologic complications in patients with sickle cell disease undergoing hematopoietic progenitor cell transplantation. Lancet Haematol 4: e553- e561, 2017

Srivastava K, Lee E, Owens E, Rujirojindakul P, Flegel WA. Full length nucleotide sequence of ERMAP alleles encoding Scianna (SC) antigens. Transfusion 56: 3-47 – 3054, 2016

Srivastava K, Polin H, Sheldon SL, Wagner FF, Grabmer C, Gabriel C, Denomme GA, Flegel WA. The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens. Transfusion 56: 2520 – 2531, 2016

Chen Q, Srivastava K, Ardinski SC, Lam K, Huvard MJ, Schmid P, Flegel WA. Full-length nucleotide sequence of 30 common SLC44A2 alleles encoding human neutrophil antigen-3 (HNA-3). Transfusion 56: 729 – 736, 2016

Flegel WA, Gottschall JL, Denomme GA. Integrating red cell genotyping into the blood supply chain: a population-based study. Lancet Haematol 2: e282 – e288, 2015

Flegel WA, Gottschall JL, Denomme GA. Implementing mass-scale red cell genotyping at a blood center. Transfusion 55: 2610 – 2615, 2015

Srivastava K, Almarry NS, Flegel WA. Genetic variation of the whole ICAM4 gene in Caucasians and African Americans. Transfusion 54: 2315 – 2324, 2014

Rujirojindakul P, Flegel WA. Applying molecular immunohematology to regularly transfused thalassemic patients in Thailand. Blood Transfusion 12: 28 – 35, 2014

Flegel WA, Chiosea I, Sachs UJ, Bein G. External quality assessment in molecular immunohematology: the INSTAND proficiency test program. Transfusion 53: 2850 – 2858, 2013

Schmid P, Flegel WA. Codon usage in vertebrates is optimized for a low risk of acquiring nonsense mutations. J Transl Med 9: 87, 2011

Schäfer R, Schnaidt M, Klaffschenkel RA, Siegel G, Schüle M, Rädlein MA, Hermanutz-Klein U, Ayturan M, Buadze M, Gassner C, Danielyan L, Kluba T, Northoff H, Flegel WA. Expression of blood group genes by mesenchymal stem cells. Br J Haematol 153: 520 – 528, 2011

Schwartz, S, Vergoulidou,M, Schreier, E, Loddenkemper,C, Reinwald,M, Schmidt-Hieber M, Flegel WA, Thiel E, Schneider T. Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood 117, 5850 – 5856, 2011

Fasano RM, Monaco A, Riehm Meier E, Pary P, Lee-Stroka AH, Otridge J, Klein HG, Marincola FM, Kamani NR, Luban NLC, Stroncek D, Flegel WA. RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management. Blood 116, 2836 – 2838, 2010

Flegel WA, von Zabern I, Doescher A, Wagner FF, Strathmann KP, Geisen C, Palfi M, Písacka M, Poole J, Polin H, Gabriel C, Avent ND. D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters. Transfusion 49, 1059 – 1069, 2009

Flegel WA, von Zabern I, Wagner FF. Six years' experience performing RHD genotyping to confirm D– red blood cell units in Germany for preventing anti-D Immunizations. Transfusion 49, 465 – 471, 2009

Lüttringhaus TA, Cho D, Ryang DW, Flegel WA. A simple RHD genotyping strategy for D– East Asian persons applied to Korean blood donors. Transfusion 46, 2128 - 2137, 2006

Wagner FF, Moulds JM, Flegel WA. Genetic mechanisms of Rhesus box variation. Transfusion 45, 338 – 344, 2005

Wagner FF, Poole J, Flegel WA. Scianna antigens including Rd are expressed by ERMAP. Blood 101, 752 - 757, 2003

Wagner FF, Eicher NI, Jørgensen JR, Lonicer CB, Flegel WA. DNB: a partial D with anti-D frequent in Central Europe. Blood 100, 2253 – 2256, 2002

Wagner FF, Ladewig B, Angert KS, Heymann GA, Eicher NI, Flegel WA. DAU allele cluster of the RHD gene. Blood 100, 306 – 311, 2002

Flegel WA, Curin-Šerbec V, Delamaire M, Donvito B, Ikeda H, Jørgensen J, Kumpel B, Le Pennec P-Y, Písacka M, Tani Y, Uchikawa M, Wendel S, Wagner FF. Rhesus index and antigen density: An analysis of the reproducibility of flow cytometric determination (Section 1B: Rh flow cytometry – Coordinator's report). Transf Clin Biol 9, 33 – 42, 2002

Wagner FF, Frohmajer A, Flegel WA. RHD positive alleles in D negative whites. BMC Genetics 2, 10, 2001

Wagner FF, Flegel WA: RHD gene deletion occurred in the Rhesus box. Blood 95, 3662 - 3668, 2000

Wagner FF, Frohmajer A, Ladewig B, Eicher NI, Lonicer CB, Müller TH, Siegel MH, Flegel WA. Weak D alleles express distinct phenotypes. Blood 95, 2699 - 2708, 2000

Flegel WA, Khull SR, Wagner FF. Primary anti-D immunization by weak D type 2 RBCs. Transfusion 40, 428 - 424, 2000

Flegel WA, Besenfelder W, Wagner FF. Predicting a donor's likelihood of donating within a preselected time interval. Transfusion Medicine 10, 181 - 192, 2000

Wagner FF, Gassner C, Müller TH, Schönitzer D, Schunter F, Flegel WA. Molecular basis of weak D phenotypes. Blood 93, 385 - 393, 1999

Wagner FF, Gassner C, Müller TH, Schönitzer D, Schunter F, Flegel WA. Three molecular structures cause Rhesus D category VI phenotypes with distinct immunohematologic features. Blood 91, 2157 - 2168, 1998

Wagner FF, Flegel WA. Polymorphism of the h allele and the population frequency of non-functional alleles. Transfusion 37, 284 - 290, 1997

Wagner, FF, Flegel, WA: Toxic epidermic necrolysis. N Engl J Med 334, 922, 1996

Wagner FF, Flegel WA. Transfusion-associated graft-versus-host disease: risk in transfusions due to homozygous HLA-haplotypes. Transfusion 35, 284 - 291, 1995

Flegel WA, Singson AW, Margolis JA, Bang AG, Posakony JW, Murre C. Dpbx, a new homeobox gene related to the human proto-oncogene pbx1: Molecular structure and developmental expression. Mech Dev 41, 155 - 161, 1993

Kniep B, Flegel WA, Northoff H, Rieber EP. CDw60 antigens of human leukocytes: Structural characterization and cellular distribution. Blood 82, 1776-1786, 1993

Flegel WA, Müller F, Däubener W, Fischer H-G, Hadding U, Northoff H. Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B. Infect Immun 59, 3659 - 3666, 1991

Flegel WA, Wölpl A, Männel DN, Northoff H. Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun 57, 2237 - 2245, 1989