George Garratty 1935–2014 Journal of Blood Group Serology and Molecular Genetics VOLUME 30, N UMBER 2, 2014 Immunohematology Journal of Blood Group Serology and Molecular Genetics Volume 30, Number 2, 2014 CONTENTS Introduction to Immunohematology Special Edition on 43 Drug-Induced Immune Cytopenias P.A. Arndt and R.M. Leger R EPORT 44 Drug-induced immune hemolytic anemia: the last 30 years of changes P. A . A r ndt R EPORT 55 Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms B.R. Curtis R EPORT 66 Drugs that have been shown to cause drug-induced immune hemolytic anemia or positive direct antiglobulin tests: some interesting findings since 2007 G. Garratty and P.A. Arndt C A SE R EPORT 80 Diagnostic pitfalls of drug-induced immune hemolytic anemia A. Salama and B. Mayer R EPORT 85 How we investigate drug-induced immune hemolytic anemia R.M. Leger, P.A. Arndt, and G. Garratty R EPORT 95 Drug-induced immune neutropenia/agranulocytosis B.R. Curtis 102 A NNOUNCEMENTS 105 A DVERT I SEMENTS 109 I NSTRUCT I ONS FOR A UTHORS E D I TOR - I N -C H I EF E D I TOR ia L B OA RD Sandra Nance, MS, MT(ASCP)SBB Philadelphia, Pennsylvania Patricia Arndt, MT(ASCP)SBB Thierry Peyrard, PharmD, PhD Pomona, California Paris, France M A N AG I NG E D I TOR Barbara J. Bryant, MD Mark Popovsky, MD Cynthia Flickinger, MT(ASCP)SBB Milwaukee, Wisconsin Braintree, Massachusetts Philadelphia, Pennsylvania Lilian Castilho, PhD S. Gerald Sandler, MD Campinas, Brazil Washington, District of Columbia TECHN I C A L E D I TORS Christine Lomas-Francis, MSc Martha R. Combs, MT(ASCP)SBB Jill R. Storry, PhD New York City, New York Durham, North Carolina Lund, Sweden Joyce Poole, FIBMS Geoffrey Daniels, PhD David F. Stroncek, MD Bristol, United Kingdom Bristol, United Kingdom Bethesda, Maryland Dawn M. Rumsey, ART(CSMLT) Anne F. Eder, MD Nicole Thornton Washington, District of Columbia Bristol, United Kingdom Norcross, Georgia Brenda J. Grossman, MD S EN I OR M ED I C A L E D I TOR St. Louis, Missouri E MER I TUS E D I TORS Ralph R. Vassallo, MD Christine Lomas-Francis, MSc Delores Mallory, MT(ASCP) SBB Philadelphia, Pennsylvania New York City, New York Supply, North Carolina Geralyn M. Meny, MD Marion E. Reid, PhD, FIBMS A SSOC iaTE M ED I C A L E D I TORS San Antonio, Texas New York City, New York P. Dayand Borge, MD Baltimore, Maryland Paul M. Ness, MD Baltimore, Maryland David Moolten, MD Philadelphia, Pennsylvania M OLECUL A R E D I TOR Margaret A. Keller Philadelphia, Pennsylvania Immunohematology is published quarterly (March, June, September, and December) by the E D I TOR ia L A SS I STA NT American Red Cross, National Headquarters, Washington, DC 20006. Sheetal Patel Immunohematology is indexed and included in Index Medicus and MEDLINE on the MEDLARS system. The contents are also cited in the EBASE/Excerpta Medica and Elsevier P RODUCT I ON A SS I STA NT BIOBASE/Current Awareness in Biological Sciences (CABS) databases. Marge Manigly The subscription price is $50 for individual, $100 for institution (U.S.) and $60 for individual, $100 for institution (foreign) per year. C OPY E D I TOR Subscriptions, Change of Address, and Extra Copies: Mary L. Tod Immunohematology, P.O. Box 40325 Philadelphia, PA 19106 P ROOFRE A DER Wendy Martin-Shuma Or call (215) 451-4902 Web site: www.redcross.org/about-us/publications/immunohematology E LECTRON I C P UBL I SHER Copyright 2014 by The American National Red Cross Paul Duquette ISSN 0894-203X O N O UR C OVER George Garratty was my boss, my mentor, and, later, my friend. He instilled in each of his staff the requirement to associate clinical findings with laboratory and serologic findings and that these aspects contributed to optimal care of patients with immune hemolytic anemias. In his preface to Immunobiology of Transfusion Medicine, published in 1994, he said, “Avoiding the immune destruction of circulating cells such as erythrocytes, leukocytes, and platelets is one of the major goals of transfusion medicine. The in vivo and in vitro reactions involved in these immune reactions provide easily studied human models for complement- and macrophage-mediated cell destruction, autoimmunity, and drug-induced immune destruction of cells. Although complement-mediated cell destruction is understood quite well, many aspects of the more common extravascular destruction of blood cells are still not understood. Over the last four decades, we have learned that important factors such as immunoglobulin class and subclass, complement-activating ability of the antibody, quantity of cell-bound antibody and complement components, affinity of the antibody, and activity of the mononuclear phagocyte system all play a role, but there are still many anomalies between the observed in vivo destruction and our in vitro results. We need to reconcile these differences before in vitro assays can be improved and to forecast accurately the survival of transfused cellular components.” We miss his presence among us. Sandra Nance, MS, MT(ASCP)SBB Senior Director, Immunohematology Reference Laboratory (IRL)/ National Reference Laboratory for Blood Group Serology (NRLBGS), American Red Cross Biomedical Services Introduction to Immunohematology Special Edition on Drug-Induced Immune Cytopenias This issue of Immunohematology on drug-induced of the changes seen with DIIHA during the last 30 years. The immune cytopenias (hemolytic anemia, thrombocytopenia, article by Gina Leger, Pat Arndt, and Dr. Garratty describes and neutropenia) was organized and guest edited by the late in detail how Dr. Garratty’s laboratory investigates DIIHA; Dr. George Garratty. Dr. Garratty started writing regular there are differences in how laboratories perform testing for reviews for Immunohematology on drug-induced immune DIIHA (e.g., gel vs. tube; untreated vs. enzyme-treated red hemolytic anemia (DIIHA) and positive direct antiglobulin blood cells), which could affect the results. The article by Dr. tests in 1985. His first review covered “some controversies, Abdulgabar Salama and Dr. Beate Mayer covers some of the unusual aspects, or subjects that have not been thoroughly pitfalls and errors they have observed that occur both clinically discussed before” and included a table with 45 drugs. The and in the laboratory that can result in misdiagnosis or lack second review 4 years later concentrated on mechanisms and of serologic evaluation for DIIHA. Rounding out the drug- ended with the statement “[i]t seems to me that in 1989 we induced cytopenias are two thorough reviews by Dr. Brian still have more questions than answers.” In his 1994 review, Curtis on drug-induced immune thrombocytopenia (DIIT) Dr. Garratty updated information on current theories about and drug-induced immune neutropenia (DIIN). Some of the DIIHA and included a table with 76 drugs. In 2004, about 100 same drugs are found in association with DIIHA, DIIT, and drugs had been associated with DIIHA, but a large number of DIIN, but usually not in the same patients. Other similarities DIIHAs were associated with cephalosporins so they were the can be seen among these three different types of drug-induced emphasis of the review that year. With regard to mechanisms immune cytopenias. of DIIHA, Dr. Garratty stated that “personally I do not think Unfortunately, Dr. Garratty passed away during the final that, in 2004, we have any better explanations tha[n] we did preparation of this issue. His reviews and other publications in 1994!” The most recent review in 2007 was by Dr. Garratty on DIIHA have been a valuable source of information for and Pat Arndt and included three tables: the first table clinicians and laboratory scientists for almost 40 years. It is contained information on 108 drugs associated with drug- fitting that this issue ofImmunohematology is published as a dependent antibodies, the second table listed 17 drugs possibly tribute to him. or probably associated with drug-independent antibodies (autoantibodies), and the third table showed 9 drugs that had Patricia A. (Pat) Arndt been shown to cause nonimmunologic protein adsorption. Regina M. (Gina) Leger This issue contains the final installment of this series of Immunohematology Research Laboratory reviews by Dr. Garratty. The review by Dr. Garratty and Pat American Red Cross Blood Services Arndt updates the three previous tables and summarizes new Southern California Region information on drugs currently associated with DIIHA. In 100 Red Cross Circle addition, in this issue, there are three others articles on DIIHA. Pomona, CA 91768 The article by Pat Arndt is a written version of her Sally Frank Award Lecture given at the 2012 AABB meeting; it covers some IMMUNOHEMATOLOGY, Volume 30, Number 2, 2014 43 R EPO R T Sally Frank Memorial Award and Lectureship* Drug-induced immune hemolytic anemia: the last 30 years of changes P.A. Arndt Drug-induced immune hemolytic anemia (DIIHA) is a rare time saw many changes relating to DIIHA. This presentation condition that occurs primarily as a result of drug-induced will review some of those changes. antibodies, either drug-dependent or drug-independent. Drug- dependent antibodies can be detected by testing drug-treated red blood cells (RBCs) or untreated RBCs in the presence of Background a solution of drug. Drug-independent antibodies react with untreated RBCs (no drug added) and cannot be distinguished The incidence of DIIHA is unknown, but Dr. Garratty from warm autoantibodies. Many changes have occurred during 1 the last 30 years, such as which drugs most commonly cause suggested that it may be about 1 in a million. Causes of DIIHA DIIHA, the optimal testing methods for identifying them, and can be classified into two broad categories: drug-induced the theories behind the mechanisms by which they react.