Blood Transfusion: New

Topics and Old

Huntsville District Memorial Hospital December 5, 2018

Allison Collins MD FRCPC allison.collins@sw.ca

Blood Transfusion: New

Topics and Old

South Muskoka Memorial Hospital December 6, 2018

Allison Collins MD FRCPC allison.collins@sw.ca

Program Planning Committee

(PPC) Disclosure

The following steps have been taken to mitigate bias:

All PPC members and speakers have signed a COI form.

All speakers have been emailed the cert i f ication/accreditation requirements for

their presentation.

Each presentation wil l be reviewed by the academic coordinator prior to i ts

delivery. The coordinator wil l be looking for any signs of bias including use of

brand names and logos of pharmaceutical companies.

I f bias is detected the PPC would review it and the speaker would be notif ied so

that the bias can be corrected before the presentation is given. I f the bias cannot

be corrected or removed the session would be cancelled.

I f a bias is detected by a planning committee member during the presentation they

would question the speaker about i t .

All biases would be reviewed at the next PPC meeting.

Disclosures

• No conflicts of interest to declare

• ORBCoN is funded by the Ministry of

Health and Long Term Care

Objectives

1. Describe the 7 important elements of a Massive

Hemorrhage Protocol

• homework: find out how many massive

hemorrhages you have in a year and how

much blood you used for them

2. Explain the responsibilities of physicians and

nurses in obtaining consent for transfusion

3. List the two mammals who regularly remove

blood from other mammals

Massive Transfusion - Definitions

• Definitions vary:

– replacement of total blood volume in < 24 hr

– replacement of > 50% of blood volume in 3 hr

– ≥ 10 U RBC in 24 hrs

– bleeding rate of ≥ 150 mL/min

• These are reasonable for retrospective reviews

but not practical in ‘real time’

– 1U q2h x 20hrs ≠ 10U over 2 hrs

• Consider a 4U RBC order as a potential massive

transfusion

Pohlman. Blood Reviews 2015;29:251

Massive Transfusion Situations

• Trauma

• Upper GI bleeds

• Obstetrical catastrophe

• Surgical misadventure

• Vascular catastrophe

• Surgery: cardiac, vascular

• Complex situations with high mortality

– e.g. 50% mortality in trauma

These patients may have:

• Mechanical bleeding

• Coagulopathy

Massive Hemorrhage Protocol (MHP)

• An algorithm for management of a

massive hemorrhage

• May improve patient outcomes, including

mortality

– standardised care

– improved communication and coordination

– improved quality and safety of patient care

• Reduces wastage of blood components

Pavenski. CSTM meeting May 2015

Goals of a MHP

To improve patient outcomes including mortality – Specific Goals: early source control of bleeding,

monitoring of relevant hemostatic and physiological

parameters, transfusion, and supportive care

– General Goals: translate best evidence and best

practices, standardize care, improve communication

and coordination within a multi-disciplinary team,

reduce overtransfusion, reduce treatment

complications, and reduce wastage of blood

components

Slide credits next slides: Drs J. Callum and K. Pavenski

Where are we now?

• How many hospitals actually have a MHP?

• Staff confusion – staff who work/train in multiple hospitals

• Different names: MHO, MTP, code omega etc.

• Different activation route: written vs. verbal order, code (silent

vs. overhead)

• Different activation criteria

• Different contents of packs

– Different amounts/ratios of RBC and plasma

– Platelets and cryoprecipitate on demand vs. fixed

• Different monitoring, including patient temperature, labs

• Different team members (e.g. porter vs. no porter)

Chin et al. Injury (epub) https://doi.org/10.1016/j.injury.2018.11.026

Where are we now?

• Different (and perhaps outdated?) transfusion goals

• Different transfusion rules

• Issuing only O Rh negative RBC in emergencies (regardless of

recipient’s age and gender)

• 2 O Rh positive and 2 O Rh negative -> unable to interpret Rh

• Never switching to group specific components

• Different supportive care: TXA (not given or given too late),

temperature (not measured and not corrected), anticoagulant

reversal (not done), crystalloid (given too much)

• Different (and generally poor) records, challenging transfer of care

• No ability to compare to peers

Chin et al. Injury (epub) https://doi.org/10.1016/j.injury.2018.11.026

The T7 of a MHP

T

1 Triggering (activation)

2 Team

3 Testing

4 Tranexamic acid

5 Temperature

6 Transfusion

7 Termination

Triggering the MHP

• Triage

– MHP are activated in highly stressful situations

– easy to believe patient at risk for haemorrhagic death

– overtransfusion common (almost never needed for GI

bleeds)

• Under-triage?

– could be catastrophic, patient bleeds to death

• Over-triage?

– overtransfusion of RBCs “because they arrived”

– TACO and other transfusion complications

– blood wastage

GI Bleeds: RBC use

Villenueva Jairath

RBC policy Restrictive

Hb < 70

Liberal

Hb < 90

Restrictive

Hb < 80

Liberal

Hb <100

RBC

U/patient

mean +/-SD

1.5 (2.3) 3.7 (3.8) 2.4 (2.6) 3.4 (3.0)

% received

plasma

6 9 N/A N/A

% received

platelets

3 4 N/A

N/A

Villenueva. NEJM 2013;368:11. Jairath. Lancet 2015;386:136

Predicting Massive Bleed – ABC Score (Assessment of Blood Consumption)

• 1 point for each of:

• Penetrating mechanism

• Positive FAST

• Systolic BP ≤ 90 mm Hg

• Heart rate ≥ 120 bpm

• FAST = Focused Assessment for

the Sonography of Trauma

(bedside ultrasound looking for

free fluid in the pericardium,

hepatorenal recess, perisplenic

space and pelvis)

• Score of ≥ 2 has 75% sensitivity

and 86% specificity for massive

transfusion

Nunez. J Trauma Inj Inf Crit Care 2009;66:346

Over activation is a problem…

Do we need a slight speed bump to give time

for MDs to decide if a MHP is likely required?

Start with 2-4 units of group O

Boutefnouchet. Injury 2015; 46: 1772

Team

BIG • Physician Lead – “Local”

• Nursing Lead

• Charting Nurse

• Code Nurse

• Anesthesia resident

• Rapid Response Team

• Porter

• MLT – BB

• MLT – Coagulation

• OB: back up anesthesia, second call OB, neonatologist, NICU RN

• Chaplain

SMALL

• Physician Lead – “Local”

• Nursing Lead

• Charting Nurse

• Code Nurse

• Anesthesia

• Porter

• MLT – BB & Coagulation

• OB: Obstetrician on call

Timing of types of testing

HOURLY

+

Group and

Screen with

first set

PLUS

& LIS ORDER SET

Blood Test Tube Top Colour

CBC Lavender

INR/PTT/fibrinogen Blue

Ionised calcium Yellow

Lactate Grey

Electrolytes and ABG ABG syringe in ice bag

Antifibrinolytics: CRASH-2 trial

• 20,211 patients randomized to placebo vs. 1+1 gram of tranexamic acid (TXA)

• sBP <90, HR >110, at risk for significant hemorrhage

• TXA reduces death rate overall (OR 0.91) and death from bleeding (OR 0.85)

• Most effective in reducing risk of death from bleeding if given within the first hour from injury (OR 0.68)

• NNT to save 1 life = 67

• No increase in arterial or venous thromboembolic complications

Shakur. Lancet 2010;376:23

Hypothermia: Prevention & Management

• Minimal number of studies

• Poorly monitored during pre-hospital and pre-OR phase

• Temp <34°C associated with an increase in mortality

• Each 1°C increases blood loss by 16% and risk of

transfusion by 22% (maintain at 36°C or higher)

• In the pre-hospital phase, trauma patients with minor

injury have a fall in temperature with passive warming

(blankets), versus a rise (and normalization) in

temperature with resistive warming blankets AND they

are more comfortable on arrival!

Reynolds. J Trauma Acute Care Surg. 2012;73:486

Dirkmann. Anesth Analg. 2008;106:1627, Kober. Mayo Clin Proc 2001;76: 369

Walpoth.NEJM 1997:337:1500, Lundgren. Scand J Trauma Resusc Emerg Med 2011;19:59.

Pre-set transfusion protocol

• Blood groups for emergency uncrossmatched

components

• Number of RBC per pack

• Ratios for extreme hemorrhages

• Targets for resuscitation based on lab testing

– Maintain Hb > 80 g/L

– Maintain platelets > 50 x 109/L (ICH > 100)

– Maintain INR less than 1.8

– Maintain fibrinogen greater than 1.5 – 2.0 g/L

– Maintain ionized calcium greater than 1.15 mmol/L

Right ratio? 30-day mortality

Holcomb. JAMA 2015;313:471 Mesar. JAMA Surg 2017;152:574

PROPPR (all trauma) Harvard (various)

trauma 1:1:1

1:1:2

Right ratio? 30-day mortality

Holcomb. JAMA 2015;313:471 Mesar. JAMA Surg 2017;152:574

PROPPR (all trauma) Harvard (various)

vascular medicine

trauma

surgery

all non-trauma*

1:1:2

1:1:1

* = 89% of 865 hemorrhages

Platelets are Pooled at CBS!

FP x 4 or 2 apheresis

PLT x 1pool or 1 apheresis

RBC x 4

1:1:1 is really 4:1:4

Don’t waste

O neg by

using it for

everybody

regardless of

age and sex

North Simcoe Muskoka

FY2014-2018

99.5% of deliveries at

age 43 years or less

Collins 2018. Data source: CIHI

Risk of D alloimmunisation

• In D neg patients who received emergency issue

uncrossmatched D pos RBC

• Range: 11% to 30.4% – 11% (Dutton. J Trauma 2005;59(6):1445)

– 11.5% (Tchakarov. Immunohematology 2014;30(4):149)

– 12.5% (Meyer. Transfusion 2015;55:791)

– 21.4% (Gonzales.Transfusion 2008;48:1318 )

– 22% (Yazer. Transfusion 2007;47:2197)

– 20-26% (Selleng. Lancet Haematology 2017;4:218)

– 30.4% (Frohn.Transfusion 2003;43:893)

• Patients with trauma/hemorrhage do not appear to form

anti-D as readily as healthy volunteers (80%)

Ontario O neg policies

Chin et al. Injury (epub) https://doi.org/10.1016/j.injury.2018.11.026

Anticoagulant “reversal”

Drug Antidote

Warfarin PCC at 1000 IU/5min

INR<3 – 1000

INR 3-5 – 2000

INR >5 – 3000

INR unknown – 2000

Dabigatran Idarucizumab 5 grams over 10 min

Apixaban PCC 2000 IU *

Rivaroxaban PCC 2000 IU *

LMWH Protamine

Heparin Protamine

* Repeat in 1 hour if still bleeding

* Note: Andexanet antidote coming for anti-Xa inhibitors

T7 Summary

T

1 Triggering

2 Team

3 Testing

4 Tranexamic acid

5 Temperature

6 Transfusion

7 Termination

Smaller = more education, team building, simple

Standard tests, consider simple POCT

“European” strategy, clear transfer of care

Towards a Provincial MHP

• U of T Rounds May 2017, Drs. Callum and Pavenski

• Survey of Ontario practice November 2017

• Delphi-method exercise by multidisciplinary panel to reach consensus on recommendations

• Transfusion Committee Forum April 2018

• Further Delphi round post-TC Forum

• External stakeholder review of 42 recommendations (TM Med Directors, Charge Techs, TAC, ENAO)

• Working groups to develop provincial protocol and toolkit 2019

Massive Hemorrhage Protocols

Presentation library > Transfusion Committee Forum

Ontario MHP

Consensus

Panel

Informed Consent

Informed Consent

1. Voluntary

2. Given by a patient with the capacity to consent

(or SDM )

3. Informed

Explain the:

• nature of the procedure

• expected benefits

• material risks and side effects

• alternatives

• likely consequences of no treatment

Justice Horace Krever 1997

Evans KG. Consent: A guide for Canadian physicians www.cmpa-acpm.ca

CMPA Risk Fact Sheet Informed Consent 2016

Informed Consent

• obtained by the practitioner proposing

the treatment/procedure, barring

emergency

• in a language the patient will

understand

• allows for questions, repetitions, and

sufficient time for assimilation

• takes place well in advance, allowing

for alternatives to allogeneic

transfusion

Justice Horace Krever 1997

Role of the Nurse

• explain the transfusion process to the patient

• determine if informed consent has been

obtained

• but not to have the informed consent discussion

and obtain the informed consent

• CNO Practice Guideline: a nurse should not

provide a treatment if there is any doubt about

whether the patient understands and is capable

of giving consent, even if there is an order

CNO Practice Guideline: Consent 2017

“The only two mammals to remove

blood regularly from other

mammals are vampire bats…and

humans”

Burnum J. NEJM 1986;314:1250

Iatrogenic Anemia

Iatrogenic Anemia

= nosocomial anemia

= investigational anemia

• Phlebotomy-related blood loss

• Not uncommon, particularly in

– critically ill patients (ICU)

– children

Causes of Anemia in Critically Ill Patients

• more than 90% anemic by day 3

• bone marrow failure

• hemolysis

• disseminated intravascular coagulation

• renal failure

• sepsis

• overt or occult hemorrhage (e.g. GI bleeding, invasive procedures)

• phlebotomy for lab tests, ABGs

Phlebotomy volumes

Internal Medicine mL/day mL/stay

Smoller (NEJM 1986;314:1233) 12.4 175

Thavendiranathan (TGH 2005) (13.3) 74.6

ICU mL/day mL/stay

Smoller (US 1986) 41.5 762

Vincent (Europe 2002) 41.1 -

Chant (SMH 2006) 13.3 -

Thomas (Alberta 2009) 25 224

Corwin (USA 1995) 61-70

Other (hospital overall) mL/day mL/stay

Eyster (JAMA 1973;223:73) 54

Wisser (Clin Chem 2003;49:1651) 5 51

Most Phlebotomy Early in AMI Admission

Salisbury. Arch Int Med 2011;171:1646

Replacing Phlebotomy Losses

• Blood loss 20 mL/day can produce negative iron balance within days

• 1% red cell mass renewed daily in healthy individual

• = 50 mL blood/day if blood volume is 5 L

• Critically ill patients may have bone marrow depression and poor nutrition

• If the patient can’t ‘keep up’, additional measures need to be considered

Woodhouse MLO October 2001

Reducing blood loss due to lab testing

• Closed blood sampling techniques

• Small volume sample tubes

– may hide problem of over-ordering

• POCT

• Alteration of test ordering behaviour

– Batch orders

– Order sets/forms, practice guidelines

– Daily report to MDs on volumes drawn

– Variable success

Clin Chem 2003;49:1651

Am J Surg 1986;151:362

CAP Today 2010 Sept

Tinmouth CMAJ 2008;178:49

The most common indication for phlebotomy

Aryeh Shander, Anesthesiologist,

Englewood Hospital & Medical Center, NJ

and President of the Society for the

Advancement of Blood Management Sunrise!

Summary

1. MHPs should address: trigger, team,

testing, tranexamic acid, temperature,

transfusion and termination.

2. The ordering prescriber is responsible for

obtaining and documenting informed

consent for transfusion.

3. Phlebotomy blood losses may be more

serious in the ICU and pediatric

populations. Limit standing orders.

Questions?

Please consider

donating blood

or bone marrow

www.blood.ca

Please consider

registering as an

organ donor

www.beadonor.ca