Use Of Group A Plasma In Massive Transfusion Protocols

Michelle Zel ler MD FRCPC MHPE DRCPSC

McMaster University & Canadian Blood Services

GHEST Symposium September 22, 2018; Toronto

Disclosures

Pfizer Ad Board

Case 28 Year old Man post motorcycle collision

Presented to Hamilton General Hospital as a transfer from another hospital due to hemodynamic instability and need for trauma care

On route, the patient required CPR, intubation, 7 units of Group O Red Blood Cells (RBCS) and 1 unit of Group AB Frozen Plasma (FP)

On arrival, he has bilateral pneumothorax, significant intra-abdominal collections and a long bone open fracture of the femur

A massive hemorrhage protocol is initiated as he is taken emergently to the Operating Room (OR)

He was transfused…. 38 units Group O RBCs

13 doses of platelets (various groups)

22 units of Group AB Frozen/apheresis plasma

20 units of Group O Cryo

This Photo by Unknown Author is licensed under CC BY-NC

Please HELP!!! It’s Friday heading into a summer long weekend and we will have

NO more AB plasma if this keeps up!!! What should we

DO???

Objectives 1. Review indications for transfusion of AB

plasma to non-AB recipients

2. Describe current AB plasma utilization patterns

3. Debate the benefits and risks of using alternate group plasma for emergency use

This Photo by Unknown Author is licensed under CC BY-NC-ND

Potential AB Plasma Uses/Miss-uses

• Group unknown • Trauma • Bleeding

• Thawed plasma, one size fits all • Neonatal/pediatric patients • Stem cell transplant • Inventory

AB Plasma Utilization

27% increase in demand for AB plasma in 2011 when compared to 2006 data

3-4% of Canadian and American donors are group AB

What accounts for this increase? ◦ Emergency issue

◦ Massive transfusion protocols ◦ Inventory management

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Yazer et al. Transfusion. 2013;53(8):1627–1633

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Vol 58, January 2018 TRANSFUSION

HABSWIN Study Design & Methods Multicentre international retrospective study on 2014 data Phase I: Survey

An online survey was sent to a group of international hospital transfusion service directors requesting participation and recruitment of other hospitals (snowball sampling)

Survey Question Domains: 1. Demographics 2. Hospital inventory 3. Hospital policy

Phase II: Data Collection Information was collected on plasma unit and recipient ABO group, location of

transfusion and indication for using AB plasma for non-AB recipients

Participating hospitals: Brazil, Canada, Denmark, Germany, Japan, Netherlands, New Zealand, Poland, United Kingdom and Unites States

o Neonates receive only AB plasma at 13/23 (56.5%) hospitals

o Thawed plasma is stocked at 9/25 (36%) hospitals

o Of those, thawed plasma expires in 5 days at 7/8 (87.5%) of hospitals and 3 days at 1 (12.5%)

§Utility is defined as the percentage of AB plasma units transfused over the percentage of AB plasma units in stock, indicating status of demand and supply of AB plasma units.

Proportion of AB plasma units that were transfused to non-AB recipients 27% of 5541 study eligible AB plasma units were transfused to AB recipients 81.3% of 26,483 A and B units went to ABO identical recipients Considerable variability ◦ Large hospitals: 56-71%

◦ Medium hospitals: 38-96%

◦ Small hospitals: 60-77%

Number of AB plasma units issued to non-AB

recipients N = 4,045

Number of AB plasma units to recipients of any ABO

group n = 5,541

Total number of all plasma units issued (of

all ABO groups) n = 43,369

Emergency department 958 1,118 2,800 ICU of any kind except NICU 720 1,225 12,173 Operating room 544 799 5,907 Hospital ward 483 597 10,275 NICU 158 163 435 Delivery room/maternity ward 30 39 255

Interventional radiology suite 11 13 96

Outpatient clinic (including cancer outpatient area)

11 42 973

Unknown/other 5 0 15 Total number of units with location indicated n (%)

2,920 (72%) 3,996 (72%) 32,929 (76%)

Number of units without location information n (%)

1,125 (28%) 1,545 (28%) 10,440 (24%)

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Number of plasma units issued by location in the hospitals

Indication

The indication for the plasma transfusion was provided for 1,634 group AB plasma units ◦ Majority were issued emergently 1,128/1,634 (69%) ◦ Group AB units close to expiry (16.4%)

◦ Patients undergoing stem cell transplant (7.3%) ◦ Last minute plasma requests where group AB plasma was available, but not

emergency issued plasma (7.3%)

HABSWIN

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Study Summary

o AB plasma are in high demand, and often short supply o A significant proportion of AB plasma units were transfused to non-AB recipients o Is transfusing 73% of AB plasma units to non-AB recipients ideal?

Risk vs Benefit

What is the risk of an ABO incompatible plasma transfusion?

Percentages of Blood Groups in Canada (%) O A B AB 46 42 9 3

o Group A plasma contains anti-B antibodies o If given to a group B or group AB patient there is potential for: o Acute hemolytic transfusion reaction o Donor antibodies bind host RBCs; activate the complement cascade leading

to anemia, disseminated intravascular coagulation, acute renal failure, and death

https://blood.ca/en/blood/facts-about-whole-blood

Why would we consider an ABO incompatible plasma transfusion?

o We transfuse platelets containing nonidentical plasma o Incompatible hemolytic reactions are extremely rare o (1 in 9,000 incompatible platelet transfusions)

o All reports of hemolytic reactions caused by products containing Group O plasma o No documented case of hemolysis from products containing Group A plasma. o Trauma patients can develop acquired immunosuppression o Use of group O whole blood in trauma patients of unknown ABO group does not

show hemolysis or renal failure among non–group O recipients Mair B, Transfusion. 1998; 38:51Y55; Isaak EJ et al. Immunohematology. 2011;27: 61Y65;

Zielinski et al. J Trauma Acute Care Surg 2013 Volume 74 (1); McManigal S, Sims KL. Am J Clin Pathol. 1999;111:202Y206. Seheult et al. Transfus Med 2017;27:30-5

The Evidence 4 STUDIES

Single Centre Study of Group A Plasma o Retrospective review of all trauma patients receiving emergency

release plasma (Group A) from 2008 to 2011

o ABO compatibility was determined posthoc

o Of the 254 patients: o 35 (14%) received ABO-incompatible o 219 (86%) received ABO-compatible transfusions.

Zielinski et al. J Trauma Acute Care Surg 2013 Volume 74 (1)

Study #1

Multicentre Study of Group A Plasma o Retrospective study of 8 trauma centres in the US (2012-2016)

o Compared compatible vs incompatible (A plasma to Group B and AB patients) o 1573 patients; 92% compatible vs 8% (120) incompatible

o Results: o More penetrating injuries in incompatible group and more plasma given at 4 hr o No hemolytic transfusion reactions o 2 x TRALI reported - compatible group o No significant difference in ARDS, thrombotic events, sepsis, acute renal failure o No significant difference in mortality at 6 or 24 hours, nor at 28 days.

Stevens et al. 2017 J Trauma Acute Care Surg Volume 83, Number 1

Study #2

Survey on Group A Plasma in Trauma o 61 trauma centers responded (mostly Level 1)

o Most maintain an inventory of immediately available group A plasma

o 63% use group A plasma in the initial phase of the resuscitation of trauma patients of unknown ABO group

o 50% of group A plasma usage is a relatively new practice having started within the past year (January 2015)

o 62% do not limit amount of group A plasma administered to trauma patients

o Only 21% consider anti-B titer when choosing group A plasma units

Dunbar NM, Yazer MH. Transfusion 2016; 56:125-9.

Study #3

Large Multicentre Study of Group A Plasma (STAT) o Retrospectively collected data on consecutive injured group A, B, and AB

patients admitted to adult Level 1 or 2 trauma centers

o All patients had to have received at least 1 unit of group A plasma during resuscitation

o Primary endpoint was in-hospital mortality

o Results: 17 trauma centers (16 US and 1 UK) 2008-2015

o 1163 trauma patients: o 809 (70%) group A patients in the identical group o 354 (30%) group B or AB patients in the incompatible group

Dunbar et al. TRANSFUSION 2017;57

Study #4

No Significant Difference in Mortality

• 76% of participating centers did not measure anti-B titers • No reported acute hemolytic transfusion reactions

Dunbar et al. TRANSFUSION 2017;57

Limitations o Retrospective design

o No biochemical markers of hemolysis were collected

o Variable practice site to site

o Limited morbidity outcomes

Conclusion: These results support the practice of issuing thawed group A plasma for the initial resuscitation of trauma patients of

unknown ABO group.

Dunbar et al. TRANSFUSION 2017;57

Back to the case… We were provided with a reported group & screen from the peripheral hospital: patient was B positive…

Question to the Audience: What would YOU do?

1. Continue to provide AB plasma

2. Switch to A plasma 3. Switch to B plasma

This Photo by Unknown Author is licensed under CC BY-SA

Summary

AB plasma is a universal product, a limited resource and increasing in demand

3-4% of the population is group AB; >70% of AB plasma is transfused to non-AB patients

Providing non-compatible A plasma to group B and AB patients in the context of massive hemorrhage appears to be safe

Acknowledgements

Thank you to the individuals who contributed data to the HABSWIN study and to the BEST Collaborative for supporting and contributing to the study.

Thank you to the McMaster Centre for Transfusion Research for supporting my research.

Thank you to Dr. Kathryn Webert and Dr. Debra Lane for help with contents of this talk.

Thank you to YOU for participating in this Saturday event!

Questions?

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Hospital size (1st row) and utility level (2nd row) of AB plasma units