Transfusion Medicine Updates & Considerations

(Optimize & Protocolize)Michelle Zeller MD FRCPC MHPE DRCPSC

McMaster University & Canadian Blood ServicesSept 21, 2019

DisclosuresØ Pfizer Advisory BoardØ Research funding through Canadian Blood Services

Disclosures

Learning Objectives

• Review principles of Patient Blood Management (PBM)• Apply strategies for implementing PBM

– Hemoglobin optimization– Restrictive use of red blood cell transfusion

• Review principles of Massive Hemorrhage Protocol (MHP)• Recognize challenges & benefits of implementation

PATIENT BLOOD MANAGEMENT (PBM)Part One

Optimize Optimize Optimize! Don’t Give TOO Much (Make your own)!!

• Definition:– Patient blood management (PBM) is an evidence-based, multidisciplinary

approach to optimizing the care of patients who might need transfusion (AABB Definition)

• Effective PBM requires:– Multi-disciplinary approach– Appropriate transfusion indications

• Minimize blood loss• Optimize patient red cell mass

• Promotes judicious use of blood products to optimize patient outcomes and decrease adverse events.

Pre-op Peri-op Post-op

Society for the Advancement of Blood Management (SABM) 2014; Meybohmet al. Perioperative Medicine (2017) 6:5

Patient Blood Management (PBM)

Any patient who might need a transfusion

Four Principles of PBM

1. Anemia management/Optimize hemoglobin 2. Minimize blood loss/Optimize coagulation3. Limit transfusion/Blood conservation

strategies4. Patient-centered decision

Shander et al. Anesthesia & Analgesia Oct 2016 • Vol 123 (4)

Why Reduce Blood Utilization?• Hives (1 in 100)• Fever (1 in 300*RBC) (1 in 20*Plt)• Volume overload (1 in 100)

Most Common

• ABO Incompatible (1 in 40 000)• Delayed hemolytic reaction (1 in 7,000)• Anaphylaxis/Severe Allergic (1 in 40,000)• Acute lung injury (1 in 10,000)

Non-infectious

• Symptomatic bacterial contamination (1 in 250 000*RBC); (1 in 10,000* PLT) death (1 in 500 000*RBC)

• HIV (1 in 21 mil.)Infectious

Risk Vs.

BenefitRisk

Bloody Easy 4

Evidence in Support of PBM• Reduces perioperative blood loss and transfusion• Reduces perioperative morbidity • Reduces mortality • Reduced length of hospital stay• Reduced costEndorsed by WHO since 2010 (WHA63.12)• Bleeding • Transfusion • Anemia

Meybohm et al. Perioperative Medicine (2017) 6:5 [Leahy et al. 2017; Goodnough et al. 2014a; Moskowitz et al. 2010 Trentino et al. 2015]; Murphy. 2015 Transfus Clin Biol.

Improved Patient

Outcomes

Poor Patient

Outcomes

Preoperative Anemia Recommendations

Mueller JAMA 2019; Zeller JAMA 2019

How to Optimize Patient Red Cells

• Minimum 4-6 weeks • Investigation of etiology

Early Identification

• Oral (>6 wks) or IV iron (

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Muñoz M, International consensus statement on the perioperative management of anaemia and iron deficiency. Anaesthesia. 2017;72(2):233–247.

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ORBCoN & ONTraC• Ontario Regional Blood Coordinating Network (ORBCoN)

– Integrates blood management in Ontario through engagement of hospitals and Canadian Blood Services since 2006

• Ontario Transfusion Coordinators (ONTraC) Program– Provincial blood conservation program– Promotes alternatives to blood transfusion in surgical patients– Formed in 2002, supported by MOH LTC– 25 Ontario hospitals– Multidisciplinary & multifaceted blood conservation on targeted

surgeries• TKA, THA, CABG, valves, radical prostatectomy, gynecologic surgery

Transfusionontario.org

HHS RCC Utilization Total Hip Arthroplasty2015** 2014 2013 2012

# of patients 487 606 714 5570 units RCC 97% 94% 89% 80%1-2 units 2% 4% 9% 17%

3 or more units 1% 2% 2% 3%

Total Knee Arthroplasty

2015** 2014 2013 2012# of patients 757 869 1010 9140 units RCC 99% 97% 92% 83%1-2 units 1% 3% 7% 15%

3 or more units 0% 0.2% 1% 2%

HHS CABG only*

2017 2016

# of patients 906 836

0 units RCC 57% 52%

1-2 units 23% 28%

3-4 units 11% 16%

5 or more units 8% 10%

* HHS CABG only patients. Excludes all patients having valves, hemiarch and ascending aorta procedures performed at time of CABG, OR priority 1 and 2 patients, and patients involved in the TRICS study (due to predetermined transfusion trigger).

** Data for 2015 arthroplasty gathered from January 1 to September 30 only.

Data C/O Linda Pickrell

Effective Preoperative IV Iron Delivery

Essentials:• Identification and lead time• Prescriber comfort and access• Product funding• Chair access• Institutional buy-inChallenge:• Product limitations

Perioperative PBM Strategies

• Cell salvage• Antifibrinolytics• Surgical Techniques

– Minimally invasive procedures where appropriate (stent/laparoscopic procedures).

– Meticulous attention to hemostasis (Factor XIV).

Carless. 2010 Cochrane Database of Systematic Reviews; Wang 2009 Anesth Analg; Fergusson 2008 NEJM; Henry 2001 Cochrane Database of Systematic Reviews.

Postoperative Restrictive Blood Transfusion

Mueller JAMA 2019; Zeller JAMA 2019

Carson et al. NEJM 2017; 377 (13)

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Red Blood Cell IndicationsHemoglobin Level (g/L)/Patient Population Transfusion Recommendations

Any Hb with associated IDA Iron repletion in hemodynamically stable patients

Less than 70 Likely appropriate, 1 unit and reassess

Less than 75 Appropriate for patients undergoing cardiovascular surgery

Less than 80 Consider in patients with pre-existing cardiovascular disease or evidence of impaired tissue oxygenation. Transfuse 1 unit, reassess

80 - 90 Probably inappropriate, unless symptomatic or evidence of impaired tissue oxygenation. Transfuse 1 unit and reassess

Greater than 90 Most likely inappropriate, unless symptomatic or evidence of impaired tissue oxygenation. Transfuse 1 unit and reassess

Bleeding Reasonable to maintain Hb > 70 (80 for cardiovascular disease)

Inpatients with hematologic malignancy No strong recommendation to support restrictive or liberal; institutional variation 70-80/titrate to symptomsOutpatient

Carson JL et al. Ann Int Med 2012;157(1);49-58. NAC Companion Document to: “Red Blood Cell Transfusion: A Clinical Practice Guideline from the AABB” 2014. www.nacblood.ca; Choosing Wisely Canada www.choosingwiselycanada.org .

http://www.nacblood.ca/

MASSIVE HEMORRHAGE PROTOCOL (MHP)Part Deux

Protocolize, Protocolize, Protocolize! Make Sure to Give ENOUGH (of the right stuff)!

MHP Principles

• Rapid, protocolized treatment of massively bleeding patient• Early recognition and treatment of acute coagulopathy of trauma• Rapid identification and treatment of bleeding source• Rapid definitive surgical intervention• Access to hemostatic agents

– Reversal agents, TxA

Kahn, Injury, Int. J. Care Injured 44 (2013) 587–592, Milligan. Emerg Med J 2011;28:870-2, Callum CMAJ Open 2019

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

https://askhematologist.com/https://creativecommons.org/licenses/by-sa/3.0/

MHP Benefits

• Improved blood product administration • Improved patient outcomes

– reduction in multiorgan failure and infectious complications– increase in ventilator- free days

• Decreased variability of treatment• Reduced blood component wastage• Facilitates interprofessional communication • Tracking of CQI metrics

Kahn, Injury, Int. J. Care Injured 44 (2013) 587–592, Milligan. Emerg Med J 2011;28:870-2, Callum CMAJ Open 2019

Interdisciplinary Team

MHPTM

Lab

Trauma Team Sx/IR

Paging

Porter

Provincial MHP Recommendations

• Callum et al. employed a modified Delphi consensus technique to generate 42 statements and 8 quality indicators

• Participants included 36 content experts and represented diverse backgrounds; stakeholder input incorporated

• Basis for an MHP toolkit that will be available through ORBCoN

Callum 2019 CMAJ Open: http://cmajopen.ca/content/7/3/E546.figures-only

http://cmajopen.ca/content/7/3/E546.figures-only

Callum 2019 CMAJ Open

The Downside• Group AB plasma is the universal plasma group

– 73% transfused to non-AB• With increased MHP adoption there has been concurrent, disproportionate

increase in AB plasma use • In an international multicentre study, plasma transfused in the ER accounted for

the highest percentage of group AB plasma units transfused to non-AB recipients• Only 3% of Canadians are group AB

Yazer 2013 Transfusion; Zeller 2018 Transfusion

Percentages of Blood Groups in Canada (%)

O A B AB

46 42 9 3https://blood.ca/en/blood/facts-about-whole-blood

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

Plasma Distribution Trends

Q4 2017/18 (Source: Canadian Blood Services)

Group A plasma instead of AB?

• Retrospective studies of trauma patients report no significant difference in outcomes between ABO-compatible and incompatible plasma transfusions

• Survey of 61 trauma centres showed 63% use Group A plasma in initial phase of resuscitation for group unknown patients

• STAT study – retrospective study of 17 trauma centres reported on 1163 trauma patients– No significant difference in in-hospital mortality

• Use of Group A plasma in MHPs is not yet standard of care • Evidence remains retrospective and observational

Dunbar, Transfusion. 2017;57(8); Stevens J., Trauma Acute Care Surg. 2017;83(1); Dunbar, Transfusion. 2016;56(1):125–129.

Take Home Points

PBMOptimize patient’s

own red cells

Judicious use of blood products

MHPRapid

identification & treatment

Hemostatic agents

Inter-disciplinary

Team

Fe

TxA

TxA

FC

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Helpful Links

1. https://professionaleducation.blood.ca/en2. http://transfusionontario.org/en/documents/?cat=bloody_easy3. https://www.ontracprogram.com/Public.aspx

https://professionaleducation.blood.ca/enhttps://www.ontracprogram.com/Public.aspxhttps://www.ontracprogram.com/Public.aspx

Thank you

Prepared with Linda Pickrell, RN, OnTRAChttp://www.hamiltonhealthsciences.ca/documents/Patient%20Education/IronPillChoosing-th.pdf

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https://fhshc.csu.mcmaster.ca/owa/redir.aspx?SURL=oOarai7-_-0JqP9wszPeD2coD64oR9uiOzF4wNOsIwZ5AgfE51XTCGgAdAB0AHAAOgAvAC8AdwB3AHcALgBoAGEAbQBpAGwAdABvAG4AaABlAGEAbAB0AGgAcwBjAGkAZQBuAGMAZQBzAC4AYwBhAC8AZABvAGMAdQBtAGUAbgB0AHMALwBQAGEAdABpAGUAbgB0ACUAMgAwAEUAZAB1AGMAYQB0AGkAbwBuAC8ASQByAG8AbgBQAGkAbABsAEMAaABvAG8AcwBpAG4AZwAtAHQAaAAuAHAAZABmAA..&URL=http://www.hamiltonhealthsciences.ca/documents/Patient%20Education/IronPillChoosing-th.pdf

Compound Brand Name Recommended amount per dose

Infusion Time*

Availabiliy

Iron Dextran Dexiron® 100-1000g 6 hrs(+test dose)

$30/100mg

Iron Sucrose Venofer® 200-300mg 100mg/hr $40/100mgFerrous Gluconate Ferrlecit® 125mg 10 min $55/125mg

Ferumoxytol Feraheme® 510mg 15 min $40/100mgNo longer available in Canada

FerricCarboxymaltose (FC)

Injectafer®Ferinject®

500-1000mg 15 min Not yet available in Canada

Iron isomaltoside Monoferric® 1000mg >15 min HC approved

EAP Reimbursement Criteria

Ministry of Health and Long-term Care Exceptional Access Program (EAP) EAP Reimbursement Criteria for Frequently Requested Drugs

Updated: December 22, 2016