Perioperative Transfusion Stewardship

Objectives

• Discuss risks and outcomes associated with transfusion

• Describe ASPIRE transfusion measures

• Provide general recommendations based on American Society of Anesthesiologists (ASA)

Transfusion Guidelines (2015)

• Share procedure-specific considerations presented in the literature for orthopedic, cardiac,

oncologic, and general surgery

• Review best practices when transfusion cannot be avoided:

– Massive Transfusion Protocols

– Obstetric Hemorrhage Protocols (ACOG Recommendations)

• Summarize ASPIRE recommendations based on literature presented

Risks Associated with Transfusion

• Anaphylaxis

• Hemolytic transfusion reaction (HTR)

• Transfusion-associated sepsis (TAS)

• Transfusion-related acute lung injury (TRALI)

• Transfusion-associated circulatory overload

(TACO)

• Transfusion-associated graft-versus-host

disease (TA-GVHD). (ASA Task Force, 2015)

(Goodnough LT, 2012)

Approximate Risk Per-Unit Transfusion of RBCs

(Carson, 2016)

Risks of Transfusion for Noncardiac Surgery

(Glance, 2011)

Outcomes Associated with Perioperative Blood Transfusion

• More than 1 in 10 patients undergoing hepatic, pancreatic, or colorectal resection were

transfused under a liberal trigger, which was associated with worse patient outcomes and

increased institutional cost compared with the restrictive trigger group. (Ejaz, 2015)

• Patients who received one or two units of erythrocytes had a 29% increased odds of death

and a 40-90% increased odds of pulmonary, sepsis, wound, and thromboembolic. (Glance,

2011)

• 30-day mortality rate for patients who were transfused was 6.44% versus 4.26% for patients

who were not transfused. (Glance, 2011)

• Restricting blood transfusions using a restrictive trigger of ≤ 7 g/dL results in a significant

reduction in total mortality, acute coronary syndrome, pulmonary edema, re-bleeding, and

bacterial infection compared with more liberal transfusion strategy. (Salpeter, 2014)

Financial Impact: Total cost of a single unit of PRBCs

• Actual institutional acquisition costs approximately $220 per unit

• Estimated mean activity-based cost of transfusion: $760 per unit

($522-$1183) takes into account acquiring, delivering, administering,

and monitoring each transfusion. (Ejaz, 2015)

(Spahn, 2020)

Implementing Patient blood management measures has shown to reduce

transfusion of blood products and improve patient outcomes

How do we measure transfusion management quality in ASPIRE?

• TRAN 01 – measuring hematocrit (or hemoglobin) before every unit transfused

• TRAN 02 – monitoring over-transfusion by ensuring that post transfusion hematocrit (or

hemoglobin) is less than 30%

Why did we choose these measures?

• Apply to most cases where transfusions were administered

• Relatively straightforward to understand

• Data in widely contained in EHR

Transfusion Recommendations & Guidelines

ASA Practice Guidelines for Perioperative Blood Management

• Preoperative Evaluation

• Preadmission Patient Preparation

• Pre-procedure Preparation

• Intraoperative and Postoperative

Management of Blood Loss. (ASA Task

Force, 2015).

Preoperative Evaluation

Perform several days to weeks in advance, if possible.

• Review Previous Medical Records & conduct a Patient/Family Interview

 Previous blood transfusion?

 History of drug-induced coagulopathy?

 Presence of congenital coagulopathy?

 Risk factors for organ ischemia?

 History of thrombotic events?

• Review existing lab results (hemoglobin, hematocrit, coagulation profiles)

• Order additional lab tests based on patient’s condition (anemia, coagulopathy)

• Conduct physical exam (ecchymosis, petechiae, pallor)

Prior to surgery, inform patient of potential risks vs. benefit of blood transfusion and identify patient preferences.

(ASA Task Force, 2015).

Preadmission Patient Prep Recommendations

(ASA Task Force on Perioperative Blood Management, 2015)

• Prevention or reduction of perioperative anemia

– Administration of erythropoietin can reduce need for RBC transfusions in patients with perioperative

hemoglobin 10-13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac,

nonvascular surgery. (Pfizer Medical Information)

– Iron (IV infusion or daily oral administration)

• Discontinue anticoagulants/antithrombotic agents (Consider patient condition and risk factors)

– Warfarin: 5 days before surgery; check PT/INR day of surgery.

– Clopidogrel or other thienopyridines: Discontinue 5 days before surgery.

– Aspirin: Discontinue 7-10 days before surgery.

• Preadmission autologous blood donation (PAD)

– Though autologous blood donation can reduce the use of allogenic blood transfusion by 40-52%, PAD is not

found to be cost-effective as compared to other blood sparing strategies. (Birkmeyer, 1993)

Pre-procedure Preparation Recommendations

Adopt Blood Management Protocols. (ASA Task Force, 2015)

• Multimodal protocol or algorithm

• Restrictive vs liberal transfusion protocol

• Non-transfusion protocol (bloodless surgery)

• Massive transfusion protocol

• Maximum surgical blood ordering schedule for elective procedures

Reversal of anticoagulants

• Vitamin K

• Prothrombin Complex Concentrates

Antifibrinolytics for prophylaxis of excessive blood loss

• Aminocaproic acid

• Tranexamic acid

Acute Normovolemic Hemodilution: Consider for cardiac and ortho procedures. (Shander,

2004)

Intraoperative and Postoperative Management of Blood Loss

• Allogenic Red Blood Cell Transfusion

– Age of Stored Blood (controversial- no conclusion)

– Leukocyte reduction: reduces complications associated with transfusion

• Reinfusion of recovered red blood cell transfusion (cell saver administration supported)

• Intraoperative and postoperative patient monitoring

– Monitor blood loss

– Perfusion of vital organs

– Anemia

– Coagulopathy

– Adverse effects of transfusion

• Treatment of excessive bleeding. (ASA Task Force, 2015)

Suggested Perioperative Blood Management

(Spahn, 2020)

Treatment of Excessive Bleeding

• ASA Practice Guidelines for Perioperative Blood Management

– Transfusion of Platelets: Obtain platelet count before transfusion

– Transfusion of FFP: Obtain coagulation tests (INR or PT and aPTT) before transfusing FFP

– Transfusion of Cryoprecipitate: Assess fibrinogen levels before giving cryo

– Pharmacologic Treatment of bleeding

– Desmopressin

– Antifibrinolytics (tranexamic acid, aminocaproic acid)

– Topical hemostatics (fibrin glue, thrombin gel)

– PCCs

– Coagulation factor concentrates (recombinant factor VIIa)

– Treatments for hypofibrinogenemia (cryoprecipitate, fibrinogen). (ASA Task Force, 2015)

Transfusion Triggers: Literature Review

Clinical Practice Guidelines from AABB (American Association of Blood Banks)

• Recommendation #1: Transfusion is not indicated until hemoglobin level is 7 g/dL for hospitalized

adult patients who are hemodynamically stable, including critically ill patients.*

• Recommendation #2: Transfusion threshold of 7-8 g/dL is indicated for patients undergoing

orthopedic or cardiac surgery, and those with preexisting cardiovascular disease.*

• Recommendation #3: Patients, including neonates, should receive RBC units selected at any point

within their licensed dating period rather than limiting patients to transfusion of only fresh (≤10

days) RBC units.

*Recommendations do not apply to patients with Acute Coronary Syndrome, severe

thrombocytopenia, and chronic transfusion-dependent anemia. (Carson, 2016; Mueller, 2019)

Transfusion Triggers: Literature Review

Red Cross Transfusion Guidelines:

• RBCs should be administered based on signs and symptoms, Hgb level, and hematologic results

• In the absence of acute hemorrhage, RBCs should be administered as single units, followed by

appropriate evaluation to justify additional units.

• Complete administration of a single unit within 4 hours

Post-transfusion Considerations:

• In a non-bleeding, non-hemolyzing adult, the hemoglobin should equilibrate within 15 minutes

after transfusion of RBCs.

• It is estimated that one RBC unit should increase Hgb by approximately 1g/dL or Hct by 3%.

(American Red Cross, 2017)

Transfusion Triggers: Literature Review

National Institute for Health and Care Excellence (NICE) Guidelines:

• Use Restrictive RBC Hgb Thresholds (7 g/dL) for patients who need RBC transfusions but do not

have:

- Major hemorrhage

- Acute Coronary Syndrome

- A need for regular blood transfusions for chronic anemia

• Post-transfusion Hgb target (goal) for restrictive therapy: 7-9 g/dL

• In patients with acute coronary syndrome, consider transfusion threshold of Hgb: 8 g/dL and

target of 8-10 g/dL

• Set individual thresholds and targets for patients with chronic anemia

• Consider single unit red blood cell transfusions for adults who do not have active bleeding

• After each single unit of RBC transfusion, clinically reassess and check Hgb levels before

administering additional units. (National Clinical Guideline Centre, 2015; Mueller, 2019)

Transfusion Trigger Considerations by Surgical Specialty

Transfusion Trigger

Recommendations

General

Surgery

Cardiac

Surgery

Orthopedic

Surgery

10%

20%

30%

40%

50%

60%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

Percentage of Cardiac Cases

Receiving a Transfusion per ASPIRE Measure Criteria

Transfusions Included Transfusions Excluded

Transfusion Literature: Cardiac Surgery

Conflicting definitions of restrictive transfusion presented in the literature:

• In a review article by Curley et al., there was no significant increase in rates of myocardial

infarction, stroke, acute renal failure, or mortality using restrictive transfusion thresholds

(Hgb: 7-9 g/dL) in patients undergoing cardiovascular surgery. (Curley, 2014)

• Low Hgb (<7) values are associated with increased operative mortality, increased likelihood

of prolonged intensive care stay and greater likelihood of postoperative hospitalization of 9

or more days. (Habib, 2003)

• Restrictive transfusion thresholds (Hgb: 7-8 g/dL) associated with higher rates of acute

coronary syndrome in anemic patients compared with more liberal transfusion thresholds

(9-10 g/dL). (Docherty, 2016)

Liberal vs. Restrictive Transfusion Strategy in Cardiac Patients

P value: 0.032

(Carson, 2013)

• 110 Patients

• Restrictive: <8 g/dL

• Liberal: <10 g/dL

• Restrictive transfusion strategy resulted in

increased rate of death (18.5% vs. 12.7%).

Transfusion Recommendations: Cardiac Surgery

Cell Saver

• Transfusion through cell saver is safe and results in a significant reduction in homologous transfusion while

not causing a clinically significant coagulopathy. Pts who receive intraoperative cell saver transfusion (ICT)

also have decreased mediastinal drainage 12 hours postoperatively. (Cote, 2016)

• Hgb levels fell significantly in patients on day 1 post-op however 24 hour postop Hgb was significantly higher

in the auto-transfusion group. (Niranjan, 2006)

• Major concerns regarding the use of cell saver include:

 Possible increase in the systemic inflammatory response. (Sandoval, 2001; Amand, 2002)

 Coagulopathy postoperatively. (Daane, 2003)

 An increased risk of fat and air emboli. (Engelhardt, 1991)

Organ Failure. (Casey, 1993; Reents, 1999)

Michigan Society of Thoracic and Cardiovascular

Surgeons (MSTCVS) &

Society of Thoracic Surgeons (STS):

Transfusion Considerations

Optimizing Perfusion: Anemia Tolerance & Transfusion

• Transfusion Trigger during CPB was 22%

• % Cr = The peak postoperative change in serum creatinine level relative to pre-CPB values.

• Acute renal injury and failure (ARF) after cardiopulmonary bypass (CPB) has been linked to

low on-pump hematocrit.

Increasing rates of AKI are seen as the

HCT dips below 20-21% during CPB.

Occurs whether the patient is

transfused or not. Transfusion itself

does increase the risk of AKI.

(Habib, 2005)

Anemia and Hypotension: Co-Occurrence during CPB

• The likelihood of acute kidney injury with CPB anemia does not change with different blood

pressure values as measured at the time when the lowest CPB hematocrit occurred.

Hypotension, Anemia Tolerance during CPB and

Postoperative Acute Kidney Injury

(Haase, 2012; Sickeler, 2014)

Hemodilution and Transfusion

Minimizing hemodilution and avoiding unnecessary transfusion is best practice.

STS Guideline Recommendations

• Multidisciplinary and multi modality:

• Mini-circuits

• Microplegia

• Modified ultrafiltration

• Blood salvage

(Society of Thoracic Surgeons Blood Conservation Guideline Task Force, 2011)

Patients with both anemia and hypotension during

CPB did not differ in rates of AKI with those of

anemia alone but did differ from patients with

hypotension alone and patients with neither

anemia or hypotension. (Sickeler, 2014)

Cardiopulmonary Bypass: Anemia, Hypotension, and AKI

Transfusion Trigger Considerations by Surgical Specialty

Transfusion Trigger

Recommendations

General

Surgery

Cardiac

Surgery

Orthopedic

Surgery

10%

15%

20%

25%

30%

35%

40%

45%

50%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

Percentage of Total Knee Arthroplasty Cases

Receiving a Transfusion per ASPIRE Measure Criteria

Transfusions Included Transfusions Excluded

Literature Review: Orthopedic Surgery

• Total Knee Replacement: Restrictive <8 g/dl and Liberal <10 g/dl

– Randomized trial looked at patients with a history of cardiovascular disease whose Hgb level was <10 after

hip fracture surgery. Randomly assigned 2016 patients to restrictive (<8) vs liberal (<10). A liberal strategy did

NOT reduce rates of death or inability to walk independently on 60 day follow up or reduce in hospital

morbidity in elderly pts at high cardiovascular risk

– No evidence found that maintaining the Hgb above 10 is superior to maintaining level of 8 with respect to

primary outcomes (death or inability to walk across the room without assistance.

– Restrictive group received 65% fewer units than liberal group. Also did not find increased rates of MI or CHF

in the liberal group.

• Hip Fracture: Restrictive: 7.3 g/dL and Liberal: 8.6 g/dL

– Liberal group was associated with a statistically significantly faster TUG (Timed Up and Go test) after hip

revision surgery compared to restrictive. The clinical importance is questionable and the groups did not differ

in Hgb at the time of testing. (Carson, 2011)

MARQCI Transfusion Recommendations

Literature Review: Orthopedic Surgery-Spine

• Purvis et al. examined 1204 patients receiving at least 1 unit of PRBCs during spine surgery.

Perioperative complications occurred in 234 patients. (Purvis, 2018)

– Findings suggest the percentage change of Hgb is independently associated with a higher risk of developing

any perioperative complication and hospital related infection.

– An Hgb decline of 50% or more was associated with an increased risk of ischemic complications and hospital

related infections.

• An additional study by Purvis et al. investigated the effects of liberal blood transfusion on

clinical outcomes of 2,374 spine surgical patients receiving transfusions. (Purvis, 2017)

– Transfusion using a liberal trigger is associated with increased morbidity, even after controlling for possible

confounders. Morbidity rates were doubled when liberal transfusions were given.

– Liberal intraop trigger: ≥10 g/dL

– Liberal postop trigger: ≥8 g/dL

– Length of stay was longer in patients transfused compared to no transfusion (5-10 days vs. 2-5 days).

Transfusion Trigger Considerations by Surgical Specialty

Transfusion Trigger

Recommendations

General

Surgery

Cardiac

Surgery

Orthopedic

Surgery

Literature Review: General Surgery

• Patients with a nadir Hgb of 8-10 undergoing colorectal, pancreatic or liver resection who

underwent a PRBC transfusion had a significantly higher LOS and overall in hospital

morbidity than those patients who were not transfused. (Ejaz, 2015)

• Among patients undergoing gastrointestinal surgery, a percentage change Hgb of 50% or

more was associated with a higher risk of postop adverse events and in particular ischemic

complications. This was true even in patients whose nadir Hgb did not drop to a restrictive

trigger concentration. (Spolverato, 2015)

• Incidence of death was significantly lower in patients receiving restrictive transfusion

compared to those receiving liberal transfusion for GI Bleed. (Villanueva, 2013; Blair, 1986)

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32

Percentage of Hysterectomy Cases

Receiving a Transfusion per ASPIRE Measure Criteria

Transfusions Included Transfusions Excluded

Literature Review: Oncology

• Periop transfusions are administered in up to 85% of patients with colorectal cancer and have

been shown to increase perioperative and postoperative morbidity and mortality. (Jakobsen,

1990)

• Preoperative anemia has been identified as an independent risk factor of poorer prognosis after

colon surgery. (Leichtle, 2011)

• de Almeida et al. studied 198 surgical oncology patients and found that 30-day mortality was

decreased in the liberal strategy group compared to the restrictive transfusion group (8.2% vs.

22.8%). (de Almeida, 2015)

• Wehry et al. examined 415 patients undergoing surgery for abdominal malignancy and found

that a restrictive transfusion protocol resulted in reduction of percentage of patients transfused

with no change in outcomes (mortality, infection, hemorrhage, LOS). (Wehry, 2015)

ASPIRE Measure: TRAN 01

Inclusions: All surgical patients receiving anesthetics who receive a transfusion of red blood cells.

Success:

Documentation of hemoglobin and/or hematocrit prior to blood transfusion

• For the first unit of transfusion, a hemoglobin or hematocrit of any value should be checked in a time period of 0 to 90

minutes before the transfusion, or the most recent documented hemoglobin or hematocrit of less than 8/24 should be

within 36 hours of the transfusion

• If the last hemoglobin or hematocrit drawn before the first transfusion is ≤ 5/16, a second unit could be administered

without rechecking hemoglobin/hematocrit

• If multiple units are administered, documentation of a hemoglobin or hematocrit value must be present within 90 minutes

before each administration

• For pediatric cases (patients < 12 years old): Pre-transfusion hemoglobin/hematocrit required before the first unit and an

additional recheck after 15cc/kg of PRBCs have been administered

• For cardiopulmonary bypass cases, all transfusions administered between cardiopulmonary bypass start and end will not

be included for determining measure results for the case

Responsible Provider: Provider(s) who administered blood product

ASPIRE Measure: TRAN 01

Exclusions:

• Massive Transfusion: Transfusion of 4 or more units of blood.

• EBL ≥ 2000 ml

• Patients < 2 years of age

• Patients <12 years old undergoing a cardiac procedure

• Patients <12 years old where either transfused PRBC or EBL was greater than 30cc/kg

• Burn cases

• ASA 5 & 6

• Labor Epidurals

• Cesarean sections with an EBL > 1500cc.

• Cesarean sections with a HR>110, SBP<85, DBP<45, or O2Sat <95%

• Postpartum hemorrhage cases

ASPIRE Measure: TRAN 02

Inclusions: Any patient that receives a red blood cell transfusion. Transfusion is defined as packed red

blood cells or whole blood

Success:

Hematocrit value documented as less than or equal to 30% and/or hemoglobin value

documented as less than or equal 10 g/dL

• All hemoglobin/hematocrit lab values drawn after the last transfusion and before anesthesia end will be

evaluated. If the lowest of these values is ≤10g/dL or ≤30%, the case will pass

• If no hemoglobin or hematocrit is drawn after the last transfusion and before anesthesia end, then the first

hemoglobin/hematocrit after anesthesia end will be evaluated. If this value is ≤10/30, the case will pass. This

measure will only examine lab values up to 6 hours after anesthesia end to identify a hemoglobin or

hematocrit value. Once the first hemoglobin or hematocrit value is identified after anesthesia end, additional

values will not be considered

• No hematocrit or hemoglobin checked within 6 hours of anesthesia end

Responsible Provider: Individual who administered the transfusion

ASPIRE Measure: TRAN 02

Exclusions:

• Patients < 2 years of age

• Patients <12 years old undergoing a cardiac procedure

• Pediatric cases (<12 years old) where either the transfused PRBC or EBL was greater than 30cc/kg

• ASA 5 & 6

• EBL ≥ 2000ml

• Massive Transfusion: Transfusion of 4 or more units of blood

• Labor Epidurals

• Cesarean sections with an EBL > 1500cc

• Cesarean sections with a HR>110, SBP<85, DBP<45, or O2Sat <95%

• Postpartum hemorrhage cases

MTQIP Transfusion Measure

For more information, visit MTQIP.

Massive Transfusion Protocols

Develop with multi-disciplinary committee that includes:

– Transfusion service/blood bank

– Emergency department

– Anesthesia

– Trauma Service

Massive Transfusion Protocol should address:

– Triggers for initiating massive transfusion in trauma

– Resuscitation in the trauma bay

• MTP Product Availability

• MTP Product Delivery

• MTP Blood Product Transfusion

– Continuing MTP in OR, Angiography suite, ICU

– Transfusion service processes for delivery of blood products

– Transfusion targets

– Use of adjuncts for massive transfusion patients

– Termination of MTP

– Performance Improvement Monitoring

For more information: American College of Surgeons

Obstetric Hemorrhage Protocol

American College of Obstetrics and Gynecology (ACOG) released the Safe Motherhood Initiative in 2013.

• Blood transfusion or cross-matching should not be used as a negative quality marker and is warranted for certain

obstetric events.

• In cases of severe obstetric hemorrhage, ≥4 units of blood products may be necessary to save the life of a

maternity patient.

• Hospitals are encouraged to coordinate efforts with their laboratories, blood banks, and quality improvement

departments to determine the appropriateness of transfusion and quantity of blood products necessary for these

patients.

For more information and resources, please visit the ACOG website: ACOG Obstetric Hemorrhage Bundle

Obstetric Hemorrhage Protocol Pocket Card

(CMQCC, 2015)

ASPIRE Recommendations

• Use the literature to develop evidence-based institution transfusion protocols and guidelines

• Restrictive transfusion protocols should be considered for asymptomatic patients

• There is rarely an indication to transfuse any patient with a Hgb >10g/dL

• Decision to transfuse should be based on objective assessment of the patient, including

Hgb/Hct

• In the absence of acute hemorrhage, transfuse one unit at a time

• Reassess post-transfusion to determine if additional units are required

Additional Transfusion Resources

ASPIRE Transfusion Toolkit

American College of Obstetrics and Gynecology:

Maternal Safety Bundle for Obstetric

Hemorrhage

American College of Surgeons: Massive Transfusion Protocol

MARCQI: Blood Transfusion Project- Reducing Transfusion in the MARCQI Population

MTQIP: Proposal for monitoring site performance for massive transfusions (MT)

Blood Conservation in Thoracic Surgery: STS Clinical Guidelines

STS Renal Failure After Cardiac Surgery: Webinar, May 2018

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