“Blood Bank Guy Essentials” LIVE Featuring: Connie Westhoff, PhD Mark Yazer, MD Justin Kreuter, MD

#BBGuyLIVE #AABB18

Sunday, 10/14/2018 Faculty Disclosure (In compliance with ACCME policy, AABB requires the following disclosures to the session audience) • Chaffin, Westhoff, Kreuter: None • Yazer:

www.aabb.org 2 Objectives (1)

• Discuss common challenges in pretransfusion testing • Evaluate progress in implementing 2015 recommended Rh genotyping strategy for serologic weak D

www.aabb.org 3 Objectives (2)

• Describe practical strategies for managing and promoting effective use of O negative RBCs, AB plasma, and group O whole blood • Analyze how to assess your massive transfusion protocol for effectiveness and composition

www.aabb.org 4 This Session Will Be Interactive!

• Personalize

• Chat

• Ask questions

• Take notes

• Move to current slide

5 So, How Ya’ Doing?

It’s day 2 of AABB! How about a quick mood check? www.aabb.org 7 Intro to BBGuy Essentials

www.aabb.org 8 www.aabb.org 9 1646 hours of free continuing education granted

www.aabb.org 10 Have you listened to an episode of BBGuy Essentials? On a scale of 1-5 (1= Novice, 5=Pro), how would you rate your BB/TM expertise level? Dr. Connie M. Westhoff, SBB, PhD

Director, Immunohematology and Genomics New York Blood Center

www.aabb.org 13 Case 1

• 65-year-old male with GI bleed • Transfused once 5 years ago during CABG • A positive, no discrepancies

www.aabb.org 14 Case 1 (2)

All significant antibodies ruled out www.aabb.org 15 Case 1: Single Isolated Reaction Don’t worry about it Run enzyme panel Use computer crossmatch Use AHG crossmatch

www.aabb.org 16 Case 2 • 46 yo female with menorrhagia; 1 pRBC requested • 2 previous pregnancies, no previous transfusions • O positive, no discrepancies • Facility MD requires AHG XM on all cases

BUT, O+ unit is incompatible by AHG XM www.aabb.org 17 Case 2: Unexpected AHG +XM: Why? Low-frequency antibody Cold autoantibody + DAT on donor unit ABO incompatibility

www.aabb.org 18 Case 3 • 55 yo male with anemia and weakness; 1 pRBC requested • No previous transfusions • ABO discrepancy:

www.aabb.org 19 Case 3 (2)

www.aabb.org 20 Case 3 (3)

www.aabb.org 21 Case 3: Reactions at Immediate Spin Ignore; these Abs don’t matter Repeat reactions at 37C Perform cold autoadsorption Identify the antibody

www.aabb.org 22 Does your lab allow the use of “pre-warming” to remove cold antibody activity? Case 4 • 72 yo female with Alzheimer’s and lower GI bleed; family members on the way from another state • No transfusions at your facility • A positive, no discrepancies • Ab screen neg • Computer XM done, 2 RBC units given One Week Later…

www.aabb.org 24 Case 4

1+(mf) www.aabb.org Image: Wikipedia commons 25 Case 4: Hemolysis 1 week after Tx This situation is likely to be fatal RBC exchange is indicated Conservative mgmt is ok This situation reflects a basic problem with our current strategy!

www.aabb.org 26 Pre-transfusion TESTING

2015 - Only ~ 30% of induced antibodies are regularly detected by antibody screen methods VEL CD59 2012 - Review series: Blood in Press : Tormey and Hendrickson AUG

Approach to pre-transfusion testing for >70 years

36 Blood group systems (394 antigens) Cover Transfusion, Reid et al. Future Pre-transfusion Testing

- Currently sample is a “black box” - Can have antibody to any of 300+ known specificities

Transfusion medicine practice in age of genomics – Patient antigen profile - starting point of pre-transfusion testing – Know what antibodies the patient is at risk to make – One time testing – part of electronic medical record Case 5 • 65 yo female with CLL, to ER with pallor and weakness – HGB 5.4 g/dL • Transfused 3 U RBC 2 years ago with neg Ab screen • O positive, no discrepancies

www.aabb.org 29 Case 5

3+ DAT: Poly 3+, IgG 3+, C3d 1+

www.aabb.org 30 Case 5: “Everything is positive!” Recommend no transfusion Give least incompatible Perform autoadsorption Send for molecular typing

www.aabb.org 31 2014 Rh Workgroup GUIDANCE Members: ABC, CAP, AABB, ACOG, ABC, ARC, Armed Forces

Goal: To begin to phase-in the use of RHD genotyping When a encounter a weaker than expected D phenotype OR D typing discrepancy To guide decision making for transfusion and RhIG candidates

Altered RHD allele categories Partial D – missing epitopes - at risk for clinically significant allo anti-D Weak D – not missing MAJOR epitopes – not at risk for clinically significant anti-D Females: RHD genotyping: 18 months (n=352)

Not candidate for RhIG potential benefit from RhIG Potential Benefit of RHD Genotyping Pregnant Women with “weaker than expected D type” in U.S. 3,953,000 Live births

3,812,000 Pregnancies

556,500 RhD-negative (0.03%)

16,700 Serologic Weak D 24,700 unnecessary 13,360 RHD Genotyping ante- and weak D types postpartum 1, 2 or 3 RhIG injections Why concerned about excess usage of RhIG? Very safe product BUT: • a human blood product • manufactured from pooled plasma from paid donors • must be actively immunized • ethical issues when biologic products are administered unnecessarily • incident of transmission of hepatitis virus • always potential for emerging agents 2015 Recommendations

Sandler SG et al. Transfusion 2015;55:680-689 www.aabb.org 36 Has your lab implemented routine D genotyping for serologic weak D? If “No,” what is the biggest reason? Unaware of recommendation Too costly Too slow Too much trouble

www.aabb.org 38 Cost Input – CMS reimbursement Testing and Product Cost $ Range Initial Testing ABO Group 12.12 (9.09-15.15) RhD Type 12.12 (9.09-15.15) Cord Blood RhD Typing 30.33 (22.75-37.91) Rh Immune Globulin 162 (121.50-202.50) (300 μg dose) Rh Immune Globulin Administration 9.60 (7.20-12.00)

RHD Genotyping Assay 250 (100-500)

Cost-savings for health care system over treating as Rh negative when RHD genotyping is ~ $256 Financial implications of RHD genotyping of pregnant women with serologic weak D phenotype Kacker S, Vassallo R, Keller M, Westhoff CM, Frick K, Sandler S, Tobian A Transfusion 2015 Future: ALL Pregnant Women “GET THE RH TYPE RIGHT” Rh status will be determined by RHD genotyping

CURRENT LIMITATIONS - Partial D+ who type strongly D+ (partial DIIIa, DIVa) - Go undetected but would benefit from RhIG - Weak D+ who are not detected without IAT - Typed as D negative and get unnecessary RhIG Mark H. Yazer, MD

Professor of Pathology, University of Pittsburgh

www.aabb.org 41 Objectives (2)

• Describe practical strategies for managing and promoting effective use of O negative RBCs, AB plasma, and group O whole blood • Analyze how to assess your massive transfusion protocol for effectiveness and composition

www.aabb.org 42 How often would you estimate your facility uses AB plasma for non-AB patients? 10-20% 20-50% 50-80% No idea

www.aabb.org 43 HABSWIN Study Summary 25 centers/10 countries

73% to non-AB

Zeller MP et al, Transfusion 2018;58:151-157 www.aabb.org 44 Has your facility implemented the use of group A plasma for trauma/massive transfusion? If “Yes,” is group A plasma used only in trauma or any MTP (like OB or GI?) Only in trauma

In any MTP

46 17 trauma centers STAT Study Summary 354 B/AB, 809 A patients

Dunbar NM & Yazer MH, Transfusion 2017;57:1879-1884 www.aabb.org 47 Does your facility have an “Rh switching” protocol? If “Yes,” does the protocol require calling the medical director before switching? Does your facility use O+ RBCs for emergency transfusion to males and “older” females? If you use O+ RBCs for older females, what does “older” mean in your facility? 45 years old 50 years old 55 years old 60+ years old

www.aabb.org 51 2010-14 7 US, 8 International TFC Study Summary

AB+/B+

O-

US O-: Number down 9.0%, proportion up 9.3%

Yazer MH et al, Transfusion 2016;56:1963-1973 www.aabb.org 52 GROUP Study Summary 38 hospitals/11 countries

O to non-O: 11.1% O- to non-O-: 43.2%

Zeller MP et al, Transfusion 2017;57:2329-2337 www.aabb.org 53 OPTIMUS Study Summary 31 sites/475,830 RBC Tx

…overall use of O– RBCs could have been reduced by 44.5% if O+ units had been given to all O– patients at least 50 years old, 9.9% for all O– patients at least 80 years old, or 8.7% for all O– critical care patients at least 50 years old. Dunbar NM & Yazer MH, Transfusion 2018;58:1348-1355 www.aabb.org 54 O Negative Blood Supply 2017 (13%) O- RBC/WB Distribution 50 10%

45 9.4% 9.4% 9% 8.7% 40 8.4% 8% 8.1% 8.0% 8.0% 7.8% 35 7.6% 7.5% 7.7% 7% 7.3% 7.4% 7.2%

O- % of Total of O-% 30 6%

25 5%

20 4%

Thousands of Units of Thousands 15 3%

10 2%

5 1%

0 0% 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Annualized Overall blood use declining; Rh negative usage increasing Trends for Collection Management study; Transfusion. 2016 BEST Collaborative Humm…..almost all RhD negative units are CEK negative Have trauma or ER physicians asked you about implementing LTOWB at your facility? LTOWB is a reasonable and safe choice for trauma transfusion? How likely are you to implement low-titer group O whole blood for trauma in the next year? www.aabb.org Courtesy Dr. Mark Yazer 59 Objections

• Is anyone watching? (BBGE 033 Clip) • Have you done enough cases? • Lost revenue for blood centers • Others?

www.aabb.org 60 How likely are you to implement low-titer group O whole blood for trauma in the next year? Before and After

Comparison of likelihood of implementing LTOWB Before and after discussion Which of these is closest to your “massive transfusion protocol” standard product mix? 2 pRBC / 2 plasma / 1 PLT 4 pRBC / 4 plasma / 1 PLT 6 pRBC / 4 plasma / 1 PLT 6 pRBC / 6 plasma / 1 PLT

www.aabb.org 63 Does your facility use cryoprecipitate in your MTP protocol? Not at all Only when indicated by low Fbg Only when indicated by TEG/ROTEM Yes, with every or every other MTP pack

www.aabb.org 64