Immunohematology and Transfusion Medicine

Mark T. Friedman • Kamille A. WestPeyman Bizargity • Kyle AnnenJeffrey S. Jhang

Immunohematology and Transfusion MedicineA Case Study Approach

Second Edition

ISBN 978-3-319-90959-2 ISBN 978-3-319-90960-8 (eBook)https://doi.org/10.1007/978-3-319-90960-8

Library of Congress Control Number: 2018946662

© Springer International Publishing AG, part of Springer Nature 2018, corrected publication 2018This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer International Publishing AG part of Springer NatureThe registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Mark T. FriedmanIcahn School of MedicineMount Sinai Health SystemNew York, NY USA

Peyman BizargityDepartment of Molecular & Human GeneticsBaylor College of MedicineHouston, TX USA

Jeffrey S. JhangIcahn School of MedicineMount Sinai Health SystemNew York, NY USA

Kamille A. WestDepartment of Transfusion MedicineNational Institutes of Health Clinical CenterBethesda, MD USA

Kyle AnnenDepartment of PathologyChildren’s Hospital ColoradoAurora, CO USA

The authors proudly dedicate this workbook to those who have tirelessly invested their professional careers and lives working to advance the science, knowledge, and practice of blood banking, immunohematology, and transfusion medicine: to those who pioneered; to those who continue to discover and build on the foundations; and to those who will inherit the wisdom to become the innovators and educators of tomorrow…

vii

Preface

Pretransfusion testing, including ABO/Rh typing, identification of unexpected anti-bodies, and compatibility testing, is an important measure in the provision of blood that may be transfused to the patient in the safest possible manner. This brief intro-duction is not intended to give the trainee a detailed instruction on solving immuno-hematology cases; rather, it is intended to give an overview on how to approach the immunohematology problems (Chaps. 1–36) of this workbook. The authors of this workbook presume that the reader has had at least basic instruction in immunohe-matology before engaging in these cases.

Although one may be tempted to jump right to the antibody panel after noting a positive antibody screen in the presented cases, it is recommended to review the clinical history for important clues that may be helpful in solving the case. For example, a history of prior transfusions suggests that the patient could have made clinically significant alloantibodies (i.e., warm-reactive immunoglobulin [Ig]G allo-antibodies capable of causing hemolytic transfusion reactions or hemolytic disease of the fetus or newborn). Alternatively, the use of phrases such as “routine clinic visit” may suggest that the patient is clinically stable despite significant anemia. In these practice cases, as in the real medical world, obtaining clinical history is an important step not to be overlooked, though in some of these cases (as sometimes occurring in actual practice), scant history is provided.

After reviewing the medical history, the next step is to interpret the ABO/Rh typ-ing results. In most cases, this will be straightforward, though one should be alert to any discrepancy in the forward and reverse typing results. For example, noting a positive result with the A1 cell in the back type may be the result of anti-A1 antibody in an individual of A2 blood type or the result of a cold allo- or autoantibody.

Next, one should review the antibody screen. It should be noted that in this work-book, we present a two-cell screen in either standard tube or gel (column agglutina-tion) method. Although typically the antibody screen is interpreted simply as positive or negative, limited additional information can be gleaned by noting differ-ences in reactions between the two cells (i.e., whether both cells or only one cell reacting) or differences in the testing phases (i.e., if tube method is used, differences in reactions between 37 °C vs. antihuman globulin [AHG] phase). Additionally, the

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antigen profiles of the antibody screen cells are listed in the beginning, which may also provide useful information when ruling out antibodies.After review of the clinical history, ABO/Rh typing, and antibody screen, one is ready to move on to the antibody panels if performed in the case (see Fig.  1). Although traditionally one is taught to interpret the antibody panels through a pro-cess of crossing out antigens, it is prudent to first take a moment to get a “landscape” view of the panel reactions. That is, one should look to see whether there are reac-tions at cold temperatures (i.e., 4 °C, room temperature [RT], immediate spin [IS]) or warm temperatures (37 °C, IgG), whether there are many cells that are positive (perhaps all cells are positive as in a panagglutinin reaction) or only few, and whether the autocontrol is positive or negative. Such consideration may help to nar-row the possible specificities of the present antibodies. In that light, for example, if reactions are only evident at 4 °C in the panel, then warm-reactive antibodies (such as anti-D, -K, -Jka) can promptly be excluded. Finally, after this initial review, one should then move on to the methodical exclusion of antibody specificities. This is traditionally taught as “crossing out” antigens in which the reactions are negative with attention toward dosage (i.e., homozygous vs. heterozygous antigen expres-sion). Figure 2 demonstrates crossing out with respect to negative reactions, dosage, and the patient’s RBC antigen phenotype. The effect of enzyme treatment (e.g., papain or ficin) may also be of value as antibody reactivity to some antigens may be enhanced or destroyed. Ultimately, after consideration of all of the clinical informa-tion and antibody identification testing, the identity of the antibody or antibodies may be determined so that the most compatible blood can be provided for the patient in case transfusion is necessary.

In the end, these cases are not necessarily meant to be difficult (though they do become more challenging as one progresses through the workbook) but are selected based on principle to introduce the practical concepts of and methods used in immu-nohematology antibody identification. Once the learner has grasped these basic techniques, he/she can apply them to more interesting cases that may be presented to them within the actual clinical practice of the transfusion service.

Finally, Chaps. 37–56 are designed to engage the learner in other aspects encom-passing transfusion medicine including coagulation, hematopoietic stem cell trans-plantation, granulocyte transfusion, massive transfusion, therapeutic apheresis, factor concentrates, transfusion complications, patient blood management, and the approach to the bloodless patient.

New York, NY, USA Mark T. Friedman Bethesda, MD, USA Kamille A. West Houston, TX, USA Peyman BizargityAurora, CO, USA Kyle Annen New York, NY, USA Jeffrey S. Jhang

Preface

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Preface

xi

Authors’ Note

This case-based immunohematology workbook, now in its second edition with added cases and enhanced information and references, has been developed over many years and was created in response to the need to teach learners in the practical art of interpreting red cell antibody studies. Though there have been many textbook resources, both in print and more recently online, which have been published for learning facts about blood banking and transfusion medicine, there are few available resources for studying and practicing immunohematology cases. The cases pre-sented in this workbook are based on realistic clinical scenarios that one may encounter in the blood bank laboratory and transfusion service. Thus, this work-book is an excellent companion to reference texts for the practical application of learned immunohematology techniques to case-based studies in the identification of red cell antibodies and in the clinical management of patient transfusions. Educators will find this workbook to be a valuable resource among their collection of teaching tools. The questions accompanying each case are presented in an open-ended for-mat rather than in the traditional single-best-answer multiple-choice format; though some may prefer the latter format for convenience, it is wise to remember that patients do not come with multiple-choice answers. Furthermore, the open-ended style should hopefully encourage learners to engage in further reading and discus-sion of the subject matter. Over the years, many trainees in clinical pathology and hematology have benefitted from the use of this type of workbook problem-solving learning, both in the preparation for their board certification exam and for their careers, and since the publication of the first edition, the workbook has achieved international acclaim.

The authors are indebted to Sandra Gilmore, Sr. Director of Patient Blood Management/Bloodless Care in the Mount Sinai Health System, New York, NY, for her expertise on the approach to the “bloodless patient” and patient blood manage-ment in the preparation of this workbook.

xii

For questions or comments, please send e-mail to Dr. Mark Friedman at mark.friedman@mountsinai.org or follow us on our facebook page.

Table of laboratory normal values

Laboratory test Normal range

White blood cells (WBC) 3.8–9.8 K/μLHemoglobin (Hgb) 12.5–17.0 g/dLHematocrit (Hct) 34–46%Mean corpuscular volume (MCV) 80–100 fLPlatelets 150–450 K/μL (150,000–450,000/μL)Reticulocyte count 0.5–1.5%Haptoglobin 30–200 mg/dLLactate dehydrogenase (LDH) 300–600 U/LTotal bilirubin 0.2–1.3 mg/dLCreatinine 0.6–1.3 mg/dLProthrombin time (PT) 11.0–14.0 sInternational normalized ratio (INR) 1.0–1.2Activated partial thromboplastin time (aPTT) 32.0–40.0 sUrinalysis Color/Turbidity Yellow/Clear

Red blood cells (RBCs) 0–3/High power fieldUrine hemoglobin NegativeUrine myoglobin Negative

Table of RBC antigen frequencies

Blood group system AntigenFrequency (%)

Caucasian African American Asian

Rh D 85 92 99C 68 27 93c 80 96 47E 29 22 39e 98 98 96

Kell K 9 2 –k >99 >99 –

Duffy Fya 66 10 99Fyb 83 23 18.5

Kidd Jka 77 92 73Jkb 74 49 76

MNS M 78 74 –N 72 75 –S 55 31 –s 89 93 –

Kyle Annen Peyman Bizargity Mark T. Friedman Jeffrey S. Jhang Kamille A. West

Authors’ Note

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xv

1 Basic Single Antibody Identification: How Hard Can It Be? . . . . . . . 1

2 Rhesus Pieces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

3 Crossmatch Crisscross . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

4 Cold Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

5 Buried Treasure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

6 I Can “See” Clearly Now . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

7 You Really “Oughta” Get This . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

8 What the Kell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

9 EeeeeK!!! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

10 Are You Kidding? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

11 G-Force . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

12 Hide and Seek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

13 The Transfusion Reaction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

14 What’s This Junk? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

15 Playing with Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

16 The Platelet Transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

17 Differential Alloadsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

18 Hey, How Did That Antibody Get There? . . . . . . . . . . . . . . . . . . . . . . . 103

19 I Can’t Stop the Hemolysis! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

20 Just Another Autoantibody . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115

Contents

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21 I Got You Baby . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

22 “You” Got that Right . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

23 The Case of Low Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

24 The Perils of Transfusing the Sickle Cell Patient . . . . . . . . . . . . . . . . . 135

25 To KB or Not to KB, That Is the Question . . . . . . . . . . . . . . . . . . . . . . 143

26 It May Do Harm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

27 Fuggedaboutit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

28 Decisions, Decisions! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

29 Oh! Are You My Type? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

30 Gene Genius . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

31 Bad Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

32 Passengers and Hitchhikers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

33 In the Clouds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

34 How “Dara” You! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

35 Polly Wants a Cracker! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207

36 Hot and Cold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

37 Mix and Match . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

38 Golden Grans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

39 I “Pitty” Thee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233

40 All Washed Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

41 The Red Pee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

42 Baby Fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

43 Thromboelastography, My Dear Doctor . . . . . . . . . . . . . . . . . . . . . . . . 257

44 Spoiled Rotten! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263

45 Bad Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269

46 Emergency! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

47 Time to Change the Plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281

48 Do the Math! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

49 Eight is Enough! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291

50 It’s So “Vonderful” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293

Contents

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51 Cruising for a Bruising . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

52 Help, I Cannot Stop the Bleeding! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301

53 Saving Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305

54 Of Wind and Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

55 The “Unfraction” Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317

56 Holy Cow! (“I’m Bloodless”) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323

Correction to: Immunohematology and Transfusion Medicine . . . . . . . . . E1

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

Contents

xix

List of Abbreviations

ACT Activated clotting timeADAMTS13 A disintegrin and metalloproteinase with a thrombospondin type

1 motif, member 13ADSOL Additive solutionAFIA Arrayed fluorescence immunoassayAHG Antihuman globulinAIHA Autoimmune hemolytic anemiaaHUS Atypical hemolytic uremic syndromeALI Acute lung injuryAML Acute myeloid leukemiaANC Absolute neutrophil countaPTT Activated partial thromboplastin timeARDS Acute respiratory distress syndromeASFA American Society for ApheresisAST Aspartate aminotransferaseBNP Brain natriuretic peptideBPDR Biological Product Deviation ReportCABG Coronary artery bypass graftC3b, C3d, C4b Complement components 3b, 3d, 4bCBER Center for Biologics Evaluation and ResearchCC Coombs control/Check cellsCCI Corrected count incrementCDC Centers for Disease Control and PreventionCFR Code of Federal RegulationsCGD Chronic granulomatous diseaseCHF Congestive heart failureCLL Chronic lymphocytic leukemiaCMV CytomegalovirusCPB Cardiopulmonary bypassCPDA Citrate–phosphate–dextrose–adenineCPOE Computer physician order entry

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CS Cold storageC-section Cesarean sectionCT Computed tomographyDAT Direct antiglobulin testD-D d-dimerDDAVP Desmopressin acetate (arginine vasopressin)DIC Disseminated intravascular coagulationDIHA Drug-induced hemolytic anemiaD-L Donath–LandsteinerDNA Deoxyribonucleic aciddNTPs Deoxynucleoside triphosphatesDOB Date of birthDRVVT Dilute Russell viper venom testDTI Direct thrombin inhibitorDTT DithiothreitolD5W 5% dextrose in waterD10W 10% dextrose in waterECG ElectrocardiogramECMO Extracorporeal membrane oxygenationED Emergency departmentEDTA Ethylenediaminetetraacetic acidEGA EDTA glycine acidELISA Enzyme-linked immunosorbent assayF FactorFDA Food and Drug Administration (United States)FDP Fibrin degradation productsFFP Fresh frozen plasmaFMH Fetal-maternal hemorrhageFNAIT Fetal/neonatal alloimmune thrombocytopeniaFNHTR Febrile nonhemolytic transfusion reactionG-CSF Granulocyte colony-stimulating factorGERD Gastroesophageal reflux diseaseGI GastrointestinalG#P# Gravida #, Para #GPA, GPB Glycophorin A, BG6PD Glucose-6-phosphate dehydrogenaseGVHD Graft-versus-host-diseaseHBOC Hemoglobin-based oxygen carrierHBV Hepatitis B virusHct HematocritHCV Hepatitis C virusHDFN Hemolytic disease of the fetus/newbornHEMPAS Hereditary erythroblastic multinuclearity with positive acidified

serum testHgb HemoglobinHIT Heparin-induced thrombocytopenia

List of Abbreviations

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HIV Human immunodeficiency virusHLA Human leukocyte antigenHLA-PRA Human leukocyte antigen-panel reactive antibodyHNA Human neutrophil antigenHPA Human platelet antigenHSC Hematopoietic stem cellsHSCT Hematopoietic stem cell transplantHTLA High titer/low avidityHUS Hemolytic uremic syndromeIAT Indirect antiglobulin testICH Intracranial hemorrhageIgA Immunoglobulin AIgG Immunoglobulin GIgM Immunoglobulin MIL InterleukinIND Investigational new drugINR International normalized ratioIS Immediate spinISI International sensitivity indexITP Idiopathic (immune) thrombocytopenic purpuraIU International unitsIV IntravenousIVIG Intravenous immunoglobulinK Kinetic time (thromboelastography)KB Kleihauer–BetkeLDH Lactate dehydrogenaseLISS Low ionic strength solutionLMWH Low molecular weight heparinLY30 Lysis (clot lysis at 30 min—thromboelastography)m MicroscopicMA Maximum amplitude (thromboelastography)MACE Modified antigen-capture enzyme-linked immunosorbent assayMAIPA Monoclonal antibody immobilization of platelet antigensMCV Mean corpuscular volumemf Mixed fieldMICU Medical intensive care unitMPS Massively parallel sequencingMRN Medical record numberMSC Marrow stem cellsNAT Nucleic acid testNHSN National Healthcare Safety NetworkNGS Next-generation sequencingNOACS Novel anticoagulantsNT Not testedPAS Platelet additive solutionPBM Patient blood management

List of Abbreviations

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PBSC Peripheral blood stem cells (PBSC)PCC Prothrombin complex concentratePCH Paroxysmal cold hemoglobinuriaPCR (AS) Polymerase chain reaction (allele-specific)PEG Polyethylene glycolPF4 Platelet factor 4PFC PerfluorocarbonpHUS Pneumococcal-associated hemolytic uremic syndromePI Pathogen inactivationPICU Pediatric intensive care unitPLS Passenger lymphocyte syndromePRCA Pure red cell aplasiaPT Prothrombin timePTP Posttransfusion purpuraR Reaction time (thromboelastography)RBC Red blood cellRCo Ristocetin cofactorRESt Rabbit erythrocyte stromaRhAG Rh-associated glycoproteinRhIg Rh immune globulinRT Room temperatureS StrongSC1 Screen cell 1SC2 Screen cell 2SCD Sickle cell diseaseSe SecretorSNP Single nucleotide polymorphismSPRCA Solid-phase red cell adherenceSTEC Shiga toxin Escherichia coliSRA Serotonin release assayTACO Transfusion-associated circulatory overloadTA-GVHD Transfusion-associated graft-versus-host diseaseTJC The Joint CommissiontPA Tissue plasminogen activatorTPE Therapeutic plasma exchangeTRALI Transfusion-related acute lung injuryTryp TrypsinTTP Thrombotic thrombocytopenic purpuraUCBSC Umbilical cord blood stem cellsUFH Unfractionated heparinVWD/F von Willebrand disease/factorW WeakWAIHA Warm autoimmune hemolytic anemiaWBC White blood cellWBIT Wrong blood in tube

List of Abbreviations