Wednesday, May 31 2:00 PM EST (1800 GMT)

Transcription

1 Webinar: Workload Reduction in the Transfusion Service due to the Implementation of PreciseType Second Webinar Session A second session of this webinar will be hosted Wednesday, May 31 2:00 PM EST (1800 GMT) Register at the link below: Upcoming Webinar 1

2 Handouts us/pages/educational Program Handouts.aspx Continuing Education PACE, Florida and California DHS 1.0 Contact Hours Each attendee must register to receive CE at: Registration deadline is June 9, 2017 Certificates will be sent via only to those who have registered by June 23, 2017 Presentation Recording Session will be recorded and posted. Access information will be sent to each registrant when the recording becomes available No CE issued for participating in recording 2

3 Questions? You are all muted Q&A following session Type in questions Course content is for information and illustration purposes only. Immucor makes no representation or warranties about the accuracy or reliability of the information presented, and this information is not to be used for clinical or maintenance evaluations. The opinions contained in this presentation are those of the presenter and do not necessarily reflect those of Immucor. ImmuTech Webinar Immucor May 2017 Glenn Ramsey, MD Medical Director, Blood Bank Northwestern Memorial Hospital Department of Pathology, Northwestern University Chicago, IL 3

4 Introduction Winter, Wright Woods, Mettawa, IL Photos: GR 10 Objectives Review scope of BeadChip PreciseType testing Discuss published indications for RBC genotyping in patients Describe Northwestern Memorial Hospital approach Examine benefits of DNA phenotyping in subsequent workups Provide case examples Discuss questions and comments 11 RBC Antibody Workups HI STAR study Hospital Investigation of Serologic Testing and Results Mazonson P, Transfusion 2014;54:271 Four US medical centers, Boston, Dallas, Los Angeles, Richmond All serologic workups in months 79% F; 63% White/18% Af Am/10% Hisp; mean age 45 Workups per patient: 6077/3608 = 1.7 New patient / previous patient = 47% / 53% of workups Study supported by Immucor 12 4

5 Immucor BioArray PreciseType HEA Phenotypes Predicted (FDA licensed antisera available) ISBT Blood Group Antigens/Phenotypes 002 MNS M, N, S, s, U S s U S s U+ var 004 RhCE C, c, E, e, V, VS possible partial C (r S ) 005 Lutheran Lu a, Lu b 006 Kell K, k, Kp a,kp b, Js a, Js b 008 Duffy Fy a, Fy b, Fy(b+) wk Fy(a b ) (GATA 67C) 009 Kidd Jk a, Jk b 010 Diego Di a, Di b 013 Scianna SC1, SC2 014 Dombrock Do a, Do b, Hy, Jo a 015 Colton Co a, Co b 016 LW LW a, LW b 13 Immucor BioArray BeadChip TM Test DNA: Extracted Amplified Boccoz SA, Methods 2013;64: BeadChip Readout Beads with amplified DNA fluoresce Fluorescent image obtained of each patient s chip Image transmitted to BioArray to match up with bead map of that chip Analysis returned from BioArray 15 5

6 BeadChip HEA Genotyping Signal Report Rh Colton Diego Dombrock Duffy MNS Kidd Kell Lutheran LW Scianna 24 sets of probes, mostly single nucleotide polymorphism (SNP) pairs (blue/green) 16 Indications for RBC Genotyping in Transfusion Services Several centers have described various approaches Georgetown University, Washington, DC Cedars Sinai Medical Center, Los Angeles, CA Emory University, Atlanta, GA Cleveland Clinic, Cleveland, OH Pediatric hospitals Children s National Med Center, Washington, DC Children s Hospital of Boston, MA Daratumumab: Brigham & Women s, Boston, MA 17 RBC Genotyping as Reference Testing Sandler SG et al, Blood Transfus 2016;14:566 MedStar Georgetown Univ Hospital, Washington, DC Amer Red Cross National Molecular Lab, Phila, PA Send problem cases to reference lab for genotyping Examples: Rh variants with antibodies Anti e( like); anti D in D+ Transfused sickle cell patient needing matched units Anti U Ambiguous RhD typings 18 6

7 RBC Genotyping for Donor Matching to Patients Shafi H et al, Transfusion 2014;54:1212 Cedars Sinai Medical Center, Los Angeles, CA 15,000 donors/yr, 10,000 genotyped Patients genotyped: Sickle cell disease Warm or cold autoantibodies Unidentified antibodies Provide extended antigen matched units to patients at antibody risk Most such units are matched beyond CEK Including Fy, Jk, S 19 RBC Genotyping in Transfusion Recipients Fasano RM et al, Arch Pathol Lab Med 2017;141:329 Emory University & Children s Healthcare, Atlanta, GA Indications for RBC genotyping Congenital anemias Sickle cell, thalassemia, Diamond Blackfan, etc Autoantibodies obscuring alloantibody identification Multiple, unidentified or high frequency antigen alloantibodies Antibody to antigen with no typing sera (Do, Js, Kp, V) Serologic typing discrepancy or ambiguity Antibody to an apparent self antigen Unexplained Rh antibodies despite antigen matching 20 RBC Genotyping in Pretransfusion Testing Sapatnekar S, Figueroa PI, Transfusion 2014;54:1452 Cleveland Clinic, Cleveland, OH Annual: 54K RBC units, 75 80K antibody screens antibody IDs ( % of screens) 56% of extended match patients, recent txn or +DAT Indications for RBC genotyping Extended antigen match: Sickle cell, thalassemia, other chronic transfusions Autoantibodies Multiple, nonspecific or HTLA antibodies Antibodies to antigens without antisera Antibody to a self antigen 21 7

8 RBC Genotyping in Pediatric Transfusion Services Klapper E et al, in Moulds JM et al, ed, BeadChip Molecular Immunohematology, New York: Springer, 2011:57 Children s National Medical Center, Washington, DC Genotyping 1000 sickle cell patients Children s Hospital of Boston, MA Sickle cell patients and their blood donors Autoimmune hemolytic anemias 22 Daratumumab Interference in Myeloma Patients Anani WQ et al, Transfusion 2017;doi: /trf BloodCenter of Wisconsin, Milwaukee, WI Brigham & Women s Hospital, Boston, MA Workup of pretransfusion samples with anti CD38 Transfusion service approach to anti CD38 patients RBC genotyping on all new patients 23 Workload Study: Donor Testing Time study Batch testing of donors Serological phenotyping for 14 antigens Vs. BioArray DNA based phenotyping for 32 antigens 60% reduction in technologist time with BioArray 51% reduction in reagents cost LifeShare Blood Center, Shreveport, LA Allen T et al, Transfusion 2009;49(3S):135A 24 8

9 Workload/Cost Estimates: Patient Phenotyping Sickle cell patients Serological typing, antigens Vs. molecular typing for 35 antigens New York Blood Center: molecular costs 15% less Casas J, Transfusion 2015;55:1388 Puget Sound Blood Center: molecular costs 25% more Wilkinson K, Transfusion 2012;52:381 Genotyping: more information for costs of similar magnitude 25 Workload Benefits of DNA Based Phenotyping in Patients Phenotyping itself More antigen information Cost effective compared to broad serological typing But what about after the typing? 26 Antibody Identification and RBC Phenotyping Traditional Approach Identify RBC alloantibodies Serotype RBCs for antigens to which antibodies react Confirm patients are negative for expected antigens Limitations Recent transfusions complicate serotyping Ensuing workups must rule out all other common alloantibodies 27 9

10 Antibody Identification and RBC Phenotyping Traditional Approach Identify RBC alloantibodies Serotype RBCs for antigens to which antibodies react Confirm patients are negative for expected antigens Limitations Recent transfusions complicate serotyping Ensuing workups must rule out all other common alloantibodies Extended RBC DNA Phenotyping Not affected by recent transfusions Future alloantibodies generally limited to absent antigens 28 Early spring leaves, Deer Grove Preserve, Palatine, IL 29 Northwestern Memorial Hospital Transfusion Service 900 bed academic medical center, downtown Chicago Heme onc, organ transplants, surgical services, Level I trauma, medical & surgical ICUs, 12,000 deliveries/yr Transfusion service also supports 240 bed rehabilitation center No donor collections Immucor solid phase compatibility testing With PEG and LISS supplementation Previous routine full serological phenotyping in antibody problems Adopted routine Immucor BioArray genotyping (RUO) in 2012 All antibody problems not previously serotyped In vitro diagnostic PreciseType in late

11 Methods: Antibody Testing Initial antibody identification Examine 3 homozygous cells for DCcEe, Kk*, Fy a/b, Jk a/b, MNSs Also Le a/b, P 1 Subsequent antibody studies Examine one homozygous cell for each of these antigens for which patient is negative Expand testing if new reactions are seen *Anti K sought with Kk cells 31 Ruling Out Major Clinically Significant Alloantibodies: How Many? Rh Kell Duffy Kidd MNS Total Antigens C/c, E/e K Fy a / Fy b Jk a /Jk b M/N, S/s Total No # Negatives, Range Special BioArray cases Partial C: r S Fy(b ) by GATA 67C: Usually no anti Fy b S s : U or U+ var Total routine antigens for rule out testing: 13, if none known True Range: 0 7, when known 32 35% # Major Antibodies to Rule Out After DNA Phenotyping RH, K, FY, JK, MNS: 138 Patients 30% 25% 25% 30% Mean 4.8 Interquartile 4 5 % Patients 20% 15% 22% 10% 11% 9% 5% 4% 0% No. of Antigens For Which Patient Is Negative 33 11

12 35% # Additional Major Antibodies to Rule Out, After BioArray Typing RH, K, FY, JK, MNS: 138 Patients 30% 25% Known antibodies excluded 30% Mean 4.0 Interquartile % % Patients 20% 15% 20% 12% 10% 9% 5% 4% 2% 0% No. Additional Antigens for which Patient is Negative 34 Ruling Out Major Clinically Significant Alloantibodies: How Many? Total routine antigens for rule out testing: 13, if none known 138 antibody patients with PreciseType phenotyping: average of 4 additional major antibodies to rule out 35 Antibody Workup Analysis I 138 consecutive RBC antibody patients Initial workup and genotype months previously Initial workup files reviewed Recent RBC transfusions in <3 months? DAT positive for IgG? Subsequent workups sought Included rechecks on preadmission testing patients presenting for surgery 36 12

13 Antibody Workup Analysis II Antibody files retrospectively reviewed for subsequent workups Subsequent workups to rule out further antibodies One homozygous reagent RBC for DCcEe, K (Kk cell), Fy a/b, Jk a/b, MNSs; and also Le a/b, P 1 Unless unexpected reactions prompted more testing Reagent screening and panel RBCs enumerated Pre BioArray (3 to 10 day interval until next batch) Post BioArray Excluded: subsequent workups with new antibodies 37 Potential Difficulties with Serological RBC Phenotyping in 138 Patients RBC Transfusions in Prior 3 Months 26 patients (19%) IgG+ DATs 15 patients (11%) Recent Transfusions 18 (13%) Both 8(6%) IgG+ DATs 7(5%) Total 33 patients (24%) Nearest percent 38 Subsequent Workups After Initial Antibody Identifications in 138 Patients Early Re Workups in 3 10 Days Before HEA Results 33 patients (24%) Later Workups After HEA Results 48 patients (35%) Early only 20 (14%) Both 13 (9%) Later only 35 (25%) Total 68 patients (49%) Nearest percent 39 13

14 Subsequent Workups 68 patients (49%) had subsequent workups In next months after initial testing and phenotyping 44 workups: after initial workup but prior to PreciseType results 3 10 day period until batched testing Controls for comparison 117 workups done with benefit of PreciseType results

15 DNA Based Phenotyping Shortens Subsequent Antibody Workups Pre Phenotype Workups Post Phenotype Workups No. RBCs, Reagent RBCs Reagent RBCs Pre vs Post Antibodies Workups Median Mean Workups Median Mean p < > <0.003 All <10 5 p: Mann Whitney U test, statistical significance = two tailed p< NMH Transfusion Service Antibody Problem Workups 120 antibody identification workups/month Excluding obstetrical women with recent RhIG 60 workups/month with PreciseType information available 7 reagent RBCs saved per workup, from study data 60 X 7 = 420 reagent RBCs/month Equivalent of cell panels/month not needed 44 Costs of RBC Antibody Workup Tests HI STAR study Hospital Investigation of Serologic Testing and Results Mazonson P, Transfusion 2014;54:271 Four US medical centers, Boston, Dallas, Los Angeles, Richmond Direct serologic costs analyzed Selected mean costs (in 2016 dollars, US medical care costs): One serologic antigen typing: $24 (x 12 antigens = $288) Selected panel cells, 1 4 $39 Selected panel cells, 5 9 $61 Full panel $62 Study supported by Immucor 45 15

16 NMH Transfusion Service Antibody Problem Workups 120 antibody identification workups/month Excluding obstetrical women with recent RhIG 60 workups/month with PreciseType information available 7 reagent RBCs saved per workup, from study data 60 X 7 = 420 reagent RBCs/month Equivalent of cell panels/month not needed HI STAR cost data: $61 cost for 5 9 panel cells X 60 X 12= $44,000/yr in workup savings, direct costs 46 Case Examples: Sickle Cell Disease 24 yo woman Current or past antibodies to: C, E, K, Fy a, Fy b, Jk b, S, Le b Warm auto, cold auto, HTLA, Bg a, other nonspecific One year: 11 workups (+3 sent out), 17 RBC units given PreciseType: negative for C, E, K, Fy a, Fy b, Jk b, S Positive for U, Js b, Hy, Jo High frequency antigens absent in some Af Amer Heterozygous for VS Carrier for likely partial e allele No other major alloantibodies to rule out 47 Chronic Transfusion: Myelodysplastic Syndrome 66 yo woman Failed double unit umbilical cord stem cell transplant Anti K, warm auto, other nonspecific reactivity One year: 37 workups, 42 RBC units PreciseType: negative for K, E, N, s Same typing pre and post transplant: failed graft Only 3 additional major antibodies to rule out 48 16

17 Autoimmune Hemolytic Anemia 68 yo woman Acute lymphocytic leukemia Warm autoantibody (relative anti e) and cold agglutinin In 2.5 months: 11 workups (+ 4 sent out), 25 RBC units PreciseType: negative for C, K, Fy a Positive for e: likely auto anti e Only 3 additional major antibodies to rule out 49 Liver Kidney Transplant 64 yo woman Autoimmune hepatitis Anti K, M, and nonspecific reactivity In 3 months after transplant: 16 workups, 3 RBC units PreciseType: negative for K, M, C, Fy a, Fy b (GATA 67C), s Fy b rule out not needed Only 3 additional major antibodies to rule out 50 Summary DNA based RBC phenotyping efficiently obtains extended antigens Workload/cost less or comparable to serology Common indications: Multiply transfused/antigen matching Complex antibodies and daratumumab Antibody/antigen discrepancies: variants? autoantibodies? Antibody workups streamlined after phenotyping When genotyping is performed routinely Half of all workups have genotyping available Average additional antibodies to rule out: 4 instead of <13 Those workups need 41% less reagent RBCs 51 17

18 Acknowledgments Northwestern Memorial Hospital Transfusion Service Team Ricardo Sumugod, NMH Laboratory Manager Karyn Hartman, NMH Blood Bank Coordinator Paul Lindholm, MD, NMH and NU Department of Pathology 52 Questions? Summer prairie, Fort Sheridan Preserve, IL 53 Questions? You are all muted Q&A following session Type in questions 18

19 Continuing Education PACE, Florida and California DHS 1.0 Contact Hours Each attendee must register to receive CE at: Registration deadline is June 9, 2017 Certificates will be sent via only to those who have registered by June 23, 2017 Questions? You are all muted Q&A following session Type in questions Upcoming Webinar 19

20 Thank you! 20