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Massive Transfusion Protocols: Does one size really fit all?

Susan Barnett, MLS(ASCP)CM

Blood Bank Technical Specialist - Quality University of Minnesota Medical Center – Fairview

University of Minnesota Masonic Children's HospitalEmail: sbarnet3@fairview.org

Claudia S. Cohn, MD, PhDAssociate Professor of Laboratory Medicine and Pathology

Director, Blood Bank LaboratoryAssociate Director, Clinical Laboratories

Associate Director, HLA LaboratoryUniversity of Minnesota

E-mail: cscohn@umn.edu

Objectives

• Define the term massive transfusion, and describe its interdisciplinary nature.

• Discuss the rationale behind using a specific ratio of blood components during a massive transfusion protocol.

• Discuss scenarios when variations in a massive transfusion protocol may be required.

Outline

• Definition of massive transfusion protocol (MTP)

• MTP process overview• MTP data from UMMC• Case presentations• History of the MTP• What ratio to use?• Variations on the standard ratio

What is a Massive Transfusion Protocol (MTP)?

• UMMC’s Definition: Replacing a patient’s entire blood volume within 24 hours

• Purpose: – To coordinate the preparation and delivery of

blood components for massively bleeding patients– Effective treatment– Efficient utilization of resources

What happens during an MTP?• When an MTP is activated, many things need

to happen.– Goal state: well-orchestrated

– Occasionally: chaotic

What happens during an MTP?• Blood Bank/Transfusion Service

– If emergency units are needed, prepare and send immediately with runner.

– Page Blood Bank Physician on call.– Prepare and issue the first cooler (MTP set). – Stay one MTP set ahead. – Immediately after pickup, issue the next MTP set.– Continue setting up/issuing coolers until the MTP is

called off. – Notify BB Medical Director if 40 or more RBCs are

issued.

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What happens during an MTP?• Blood Bank Attending/Fellow

– Coordinate patient care with Blood Bank and MTP Nurse Coordinator.

– Bring complicated patient issues to the attention of the attending provider.

– Check for history of severe transfusion reactions.

What happens during an MTP?• Blood Components:

– Adults (35 kg): • First Cooler: 2 RBCs, 2 plasma, 1 platelet• Subsequent Coolers: 4 RBCs, 4 plasma, 1 platelet (plus

2 cryo pools with 5th cooler and every 3rd cooler after that)

– Peds (<35 kg): • Every Cooler: 2 RBCs, 2 plasma• Plus: 1 platelet every other cooler (starting with the 1st

cooler) and 1 cryo pool with 5th cooler and every 3rd

cooler after that.

• Other items:– Sent with 1st cooler: wireless phone and

laminated MTP guide

– Sent with every cooler: massive transfusion record

– Sent with 1st cooler, then all even numbered coolers: Lab tubes and order form for designated lab tests

What happens during an MTP? What happens during an MTP?

What happens during an MTP? What happens during an MTP?

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What happens during an MTP? What happens during an MTP?• Patient Care Unit (PCU)

– Physician or RN activates the MTP by calling Blood Bank.

– Request 2 emergency units, if needed.– When activated, if outside of OR/ICU, call a code

team to the unit. – Draw type and screen, if not already done.– Identify MTP Nurse Coordinator and MTP MD

Coordinator.

What happens during an MTP?• MTP Nurse Coordinator

– Coordinate the MTP at bedside.– Designate roles as needed.– Communicate with MD and BB.– Notify BB when MTP is discontinued.

• MTP MD Coordinator– Direct patient care.– Determine when MTP should be discontinued.

MTPs at UMMC (2015 to 2017)

67

90

103

0

20

40

60

80

100

120

2015 MTPs 2016 MTPs 2017 MTPs

MTPs at UMMC (2015 to 2017)

Operating Room34%

Adult ICU33%

Adult CV ICU15%

OB6%

Adult Med/Surg5%

Emergency Room

4%

Peds ICU3% Neonatal ICU

0%

MTPs at UMMC (2015 to 2017)

0

0.5

1

1.5

2

2.5

3

3.5

2015 Avg. 2016 Avg. 2017 Avg.

Issued

Used

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Case Study #1

• 39 year old female with esophageal varices, alcoholic cirrhosis, and end stage liver disease.

• Lab values prior to MTP:– Hgb = 4.1 g/dL– PLT = 41 x 109/L– Fibrinogen = 98 mg/dL– INR = 5.87

Case Study #1

• MTP activated at 0315.• First cooler picked up at 0320.• Lab values drawn at 0436:

– Hgb = 5.6 g/dL– PLT = 64 x 109/L– Fibrinogen = 139 mg/dL– INR = 2.71

Case Study #1

• Duration: ~12 hours• Total used:

– 20 RBCs– 20 plasma– 5 platelets– 2 cryo pools

• Lab values after MTP:– Hgb = 8.8 g/dL– PLT = 65 x 109/L– Fibrinogen = 212 mg/dL– INR = 2.08

Case Study #2

• 25 year old female in labor (4th pregnancy). Amniotic fluid embolism during labor, cardiac arrest, DIC. Emergent C-section.

• Lab values at the start of the MTP:– Hgb = 4.7 g/dL– PLT = 20 x 109/L– Fibrinogen = not tested– INR = >10.00

Case Study #2

• MTP activated at 0908.• 2 emergency units picked up at 0910.• First cooler picked up at 0923.• Lab values drawn at 0946:

– Hgb = 9.5 g/dL– PLT = 75 x 109/L– Fibrinogen = <61 mg/dL– INR = 3.40

• Cryoprecipitate requested early – ready and picked up at 1005.

Case Study #2

• Duration: ~5.5 hours • Total used:

– 41 RBCs– 37 plasma– 12 platelets– 4 cryo pools

• Lab values after MTP:– Hgb = 10.6 g/dL– PLT = 140 x 109/L– Fibrinogen = 245 mg/dL– INR = 0.98

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Case Study #3

• 5 year old female (18.6 kg) on ECMO, with pulmonary hemorrhage.

• Lab values ~2 hours prior to MTP:– Hgb = 12.1 g/dL– PLT = 120 x 109/L– Fibrinogen = 487 mg/dL– INR = 1.62

Case Study #3

• MTP activated at 1848.• First cooler picked up at 1853.• Lab values drawn at 1907:

– Hgb = 7.4 g/dL– PLT = 48 x 109/L

• Lab values drawn at 1950:– Hgb = 10.7 g/dL– PLT = 52 x 109/L– Fibrinogen = 169 mg/dL– INR = 1.68

Case Study #3

• Duration: ~2.5 hours • Total used:

– 14 RBCs– 13 plasma– 3 platelets– 1 cryo pools

• Lab values after MTP:– Hgb = 15.6 g/dL– PLT = 102 x 109/L– Fibrinogen = 386 mg/dL– INR = 1.06

Case Study #4

• 8 day old male (0.72 kg) born at 22 weeks gestation with necrotizing enterocolitis.

• Lab values prior to MTP:– Hgb = 13.1 g/dL– PLT = 65 x 109/L– Fibrinogen = 262 mg/dL– INR = 2.02

Case Study #4

• MTP activated at 0937.• First cooler picked up at 0946.• Lab values drawn at 1000:

– Hgb = 4.3 g/dL– PLT = 64 x 109/L– Fibrinogen = 224 mg/dL– INR = 0.92

Case Study #4

• Duration: ~0.5 hours • Total used:

– 1 RBC– 1 plasma– 1 platelet

• Lab values after MTP:– Hgb = 8.2 g/dL– No other values tested

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MTP: History• 1917 – WWI: First field transfusion

– Captain Oswald H. Robertson transfused a 14 day old O- whole blood unit during the Battle of Cambrai

New evidence in trauma resuscitation by Timothy Miller –Perioperative Medicine, 2013. and Wikipedia

• 1940s – WWII: Albumin and lyophilized plasma were used in combination with whole blood to achieve a balanced resuscitation

• 1970s – Vietnam: First use of component therapy for battlefield resuscitation

Dilutional Coagulopathy• There was an overuse of RBC and underuse of

plasma and platelets led to uncontrolled bleeding

• This led to a vicious cycle of problems that became known as the ‘lethal triad’ of trauma: coagulopathy, hypothermia and acidosis.

MTP: How Much?

• In 1990s MTPs developed to deliver “balanced” ratios of components.

• Attempts were made to recapitulate whole blood

• What were the correct ratios?

Retrospective analysis

• Holcomb found that 30-day survival was significantly increased in patients with high plasma:RBC ratios (>1:2) compared to those with low plasma:RBC ratios (<1:2).

• A combination of high plasma and high platelet ratios (>1:2) increased 6-hour, 24-hour and 30-day survival.

PROPPR Trial

• Analyzed ratios of Plasma: Platelets: RBC in a prospective randomized controlled trial

• Randomized 680 severely injured patients to receive plasma:platelets:RBC in a 1:1:1 or 1:1:2 fashion.

• Found no significant difference for 24 hour mortality• However, the 1:1:1 group had greater proportion of

hemostasis and lower mortality due to exsanguination at 24 hours.

• The timing of blood product administration was affected by the study protocol, with the 1:1:1 group likely receiving platelets earlier and the 1:1:2 group receiving plasma earlier

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Holes in the data

• Survivor bias due to the fact that many deaths occur early in the hospital course when the patients are more likely to be in the low ratio group

• A further confounding factor is that patients who have more severe injuries and receive relatively higher quantities of RBCs are both more likely to receive a lower plasma:RBCratio and are more likely to die

Mesar T1, Larentzakis A1, Dzik W2, Chang Y3, Velmahos

G1, Yeh DD1.JAMA Surg. 2017 Jun 1;152(6):574-580

• High FFP:RBC transfusion ratios are applied mostly to patients without trauma, who account for nearly 90% of all massive transfusion events. Thirty-day survival was not significantly different in patients who received a high FFP:RBC ratio compared with those who received a low ratio. Explanation of survival bias

GI bleeds Caput medusa

GI Bleeds and MTP

• Liver is the source of all clotting factors (except F8)

• Patients with a GI bleed usually need large volumes of plasma

• Consider higher ratios of plasma when GI bleeds occur

OB and MTP

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Maternal Hemorrhage

• Young healthy females• Massive, rapid blood loss• Many causes:

– Amniotic fluid embolus– Infection– Uterine atony

• Disseminated Intravascular Coagulation (DIC)

OB and DIC and fibrinogen

• Massive obstetrical bleeding reduces blood flow to the uterus.

• Subsequent tissue hypoperfusion increases the production of thrombomodulin in vascular endothelial cells and promotes the activation of protein C

• Protein C activation produces severe coagulopathies by irreversibly inhibiting F5 and F8 while simultaneously suppressing plasminogen activator inhibitor-1

Disseminated Intravascular Coagulation

• Fibrinogen rapidly depleted– Cannot form a clot

• Plasmin depleted– Cannot lyse clots

• Patient condition may rapidly deteriorate when tissue damage occurs

Anti hemophiliac factor (AHF) Cryoprecipitate

10 pools of cryo contain 2.5 grams of fibrinogen

MTP + Extra Cryoprecipitate

• One unit of fresh whole blood contains 1 gram of fibrinogen

• It is common practice to replace this loss with one unit of RBCs and one unit of fresh frozen plasma (FFP), which restores approximately 500 mg of fibrinogen

• 10 units of cryoprecipitate provides 2.5 g of fibrinogen

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Pediatric MTP Pediatric MTP

• Follow same ratios used for adult MTP• Smaller doses used• For NICU we use teeny-tiny doses

, Volume: 56, Issue: 3, Pages: 558-563, First published: 09 October 2015, DOI: (10.1111/trf.13370)

MTPs Help Save Lives

Survival after ultramassive transfusion: a review of 1360 cases

Survival after ultramassive transfusion: a review of 1360 cases, Volume: 56, Issue: 3, Pages: 558-563, First published: 09 October 2015, DOI: (10.1111/trf.13370)

Back to the Future?

• Spinella et al. compared the use of warm fresh whole blood (WFWB) to component therapy from a transfusion database at the US Army Institute of Surgical Research.

Warm Fresh Whole Blood

• Combat casualty patients from both Iraq and Afghanistan who were transfused with >1 unit of RBCs. The patients who received WFWB got on average only 30% WFWB and 70% component therapy, however their survival rate was far better than patients who had received component therapy alone.

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• Patients receiving WFWB are given 500 ml of warm blood that contains the full amount of platelets, clotting factors and fibrinogen

• Component therapy in a 1:1:1 ratio of platelets, plasma and RBCs does not contain comparable levels of platelets, clotting factors, or fibrinogen .

Back to Whole Blood?

• When components are reconstituted after the addition of anti-coagulants and additive solutions a cold, dilute product is produced.

• Therefore even best practice component therapy using the 1:1:1 formula is not as effective as fresh whole blood.

Thank you

• Q & A?