Update on Transfusion Practice Wheres the Evidence? Connie Lorette Calvin, PhD, CRNA, APRN Northeastern University.

Update on Transfusion PracticeWhere’s the Evidence?

Connie Lorette Calvin, PhD, CRNA, APRN

Northeastern University

History• Richard Lower (1631-1691)

– Performed the first transfusion (animal to animal) in 1665

– Lamb to human 1667

• 1667 Jean Baptist Denis – Lambs blood– Calves blood

• 1774 – – Lavoisier - Role of oxygen in respiration– Priestley – RBC as oxygen carriers

• 1818 - first human to human transfusion– James Blundell

Karl Landsteiner1930 Nobel Prize Laureate

• 1900 – Landsteiner– A-B-O

• 1902– Sturli & DeCastello– AB

• 1940-Landsteiner– Rh typing

Lewisohn’s Method of Transfusion1913

Blood is collected in a citrated flask….…...and immediately transfused.

Enculturation of Transfusion• Blood is a “life giving force”• 1-800-save a life

1971 - 1987

• Red cell transfusion more than doubled• Platelet transfusion grew 50 fold• Risk of hepatitis transmission was

approximately 1/100 U transfused• HIV / AIDS• Is transfusion beneficial

Transfusion Trigger

• Hemoglobin 10gm/dl• Hematocrit 30%• Blood loss of 15% of circulating blood volume• Clinical presentation

• Risk:Benefits

“Safest Blood”

• Voluntary blood donation – self exclusion• Surrogate tests• NAT

• Does transfusion of banked blood improve outcome for patients?

Infectious Risk of Transfusion

Pathogen Estimate Risk Per Unit

Hepatitis A Unknown - <1:1million

Hepatitis B 1 : 277,000

Hepatitis C 1 : 1,930,000

HIV - 1 1 : 2,135,000

HTLV -I, II 1 : 2,993,000

CMV Infrequent in leukocyte reduced components

West Nile 1 : 350,000

Infectious Risk of Transfusion

Pathogen Estimated Risk Per Unit

Bacterial contamination 1:5 million RBC

1:100,000 per apheresis or pooled platelet unit

Malaria < 1:1 million

Babesia < 1:1 million regional

Chagas Disease Unknown presumably

< 1:1 million

Variant Creutzfeldt-Jacob Disease

3 reported case in UK

Troublesome Events!

• Alloimmunization (platelets – Leukocytes - RBC) • HLA – antigens

– Granulocyte – platelet – RBC specific

• Allergic reactions• Febrile reactions • ABT – related mortality

– TRALI – TAS – HTRs – TTI

• What are the costs of these?

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TRALI -Transfusion Related Acute Lung Injury

• All plasma containing blood products• Non-cardiogenic pulmonary edema

– 1-2 hours post-transfusion – Dyspnea -cough - fever

• Misdiagnosed - TACO– Volume overload– Cardiogenic pulmonary edema

• Multiparous donors – HLA sensitization

Hemolytic Transfusion Reactions

• ABO– ABO antigens and/or antibodies to other RBC

antigens.

• Acute = 24 hours• Delayed > 24 hours• Non-ABO

– RBC antibodies• Jkb, Jka, Kell, Fya, Fyb, E, Jsa, I

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Transfusion Associated Sepsis

• Bacterial contamination• Platelets – highest

– Decreased with single-donor

• Organisms– Staphylococcus epidermidis– E-coli– Staphylococcus aureus– Bacillus cereus

Transfusion Related Immunomodulation - TRIM

• APCs and plasma – Non-specific immunosuppression– Antigen-specific immunosuppression – Impaired T-cell mediated immunity– Decreased macrophage– Altered cytokine

• Renal allografts – better outcomes• Tumor recurrence• Reduction in survival

– WBCs – HLA – CD4 – Helper T-cell

Leukocyte Reduction

• Non-hemolytic transfusion reactions• CMV transmission• HLA alloimmunization

• Capraro et al.– Infection rate– 90-day mortality– Length of ICU stay

Benefits???

Oxygen Transports

• Blood flow - CO• Arterial O2 content

– DO2 = CO X CaO2

• Transportation– Hemoglobin– Plasma– DO2 = CO X (%Sat X 1.39 X [Hb])

Impact of Anemia

• CRIT• NNE

– Lowest hct on bypass = increased mortality and incidence of heart failure

– However blood transfusions = increased need for mechanical and inotropic support

• Nadir hgb following MI predicts mortality– Aronson et al. 2007

Adaption to Anemia

• Shift in oxyhemoglobin dissociation curve– Right - synthesis 2,3-DPG

• Hemodynamic alterations– CO

• Microcirculatory alterations– Vascular tone

• Renin-angiotensin-aldosterone system

Impact of Preop Anemia on Postop Adverse Events

• Cardiac surgical patients n=5065• Low preop hgb = Comorbidities = adverse cardiac

events• Anemia = adverse postop neurologic and renal

outcomes– Kulier et al. 2007

• Preoperative anemia and intraoperative blood transfusion were both independent risk factors for adverse outcomes.

• Incidence increased significantly as a function of numbers of units of RBCs transfused

Efficacy of RBC transfusion

• DO2 and utilization = improved outcomes• Delivery - Stored RBC

– Low p50 – shift oxygen dissociation curve – left

– Depletion 2,3, DPG– Depletion ATP

• Oxygen utilization– Organ level– Hemodynamics and oxygen transport

parameters

Anemia and Transfusion

• Anemia predicts adverse outcomes• Current transfusion practice provides no benefit or is

harmful• Ischemic complications were not decreased with

blood transfusion– Murphy et al. 2007

• Patients who received blood that was stored for more than 2 weeks prior to transfusion had a statistically significant increase in in-hospital mortality, prolonged intubation, renal failure and sepsis or septicemia– Koch 2007

Storage LesionsBiochemical Changes

• Lactate = 1.6 - 30.1 mmol/L• pH = 7.2 - 6.6• 2,3-DPG • ATP • GSH • K+ = 3.9 - 78 mEq/L• SNO-Hb • Ionized Calcium and magnesium = 0• Free Hemoglobin

Regulation of microvascular perfusion mediated by Hemoglobin + NO

Low pO2Low pH

ReleaseATP

Storage LesionsBiomechanical

• Hemolysis• Membrane area • Osmotic fragility • RBC adhesion • Deformability

Storage LesionsOxidative

• Hemoglobin oxidation• Hemoglobin denaturation• Lipid peroxidation• Bioactive Substance

– Cytokines– Histamines– Lipids – Soluble HLA

Storage

• Morphologic• Biochemical • Storage duration

– Increased mortality– Increased length of stay in ICU/Hospital– Multiple organ failure– TRALI– Increased infections– Impaired tissue oxygen utilization

Benefits

• Hemorrhagic shock• Critically ill do not tolerate anemia• Goal

– Increase DO2– Increase VO2

Efficacy of RBC Transfusion in the Critically Ill

• RBC transfusion did not improve VO2• RBC transfusion was not associated with

improvements in clinical outcomes• RBC transfusion was associated with worse

outcomes• Factors to identify patients who may benefit• Lack of efficacy related to

– Adherence of stored RBCs– Nitric Oxide binding– Donor leukocytes– Inflammatory response– Decreased red cell deformability

Large Randomized Controlled Trials

• Restrictive strategies vs. liberal strategies– Carson et al. 1996

• No data demonstrating that allogeneic RBCs increase oxygen carrying capacity– Hebert et al. 1997

• Mortality rate was doubled for patients receiving perioperative transfusion– Engoren et al. 2002

• The number of RBC units transfused is an independent predictor of worse clinical outcome – Corwin et al. 2004– Corwin et al. 2007

Transfusion (1-2 U) Does Not Increase Oxygen Delivery!!

• The influence of allogeneic RBC transfusion compared with 100% oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery

• O2 - not the blood transfusion increased tissue oxygen levels

Suttner et al. (2004) anesth analg 99: 2-11

Rejuvenation

• Post-storage metabolic manipulations• Mixture of pyruvate – inosine – phosphate –

adenine – Rejuvesol (Cytosol Laboratory Inc)

• 37°C incubation followed by cell washing [24]

• Restored ATP• Elevated 2,3-DPG

Goals

• Reduce hemolysis• Reduce dead-on-arrival RBC

– Iron toxicity– Vasoconstriction via NO scavenging

• Maintain deformability / prevent aggregation– Prevent capillary blockage

• Maintenance of high ATP – 2,3, DPG – SNO-hb• Minimize oxidative damage• Prevent release, and/or remove bio-active substances

– Prevention of TRALI

• Leukoreduction, irradiation, pathogen-reduction, etc.

Hemoglobin Solutions

• Limited duration of action• Half life 10 - 30 minutes• High colloidal osmotic pressure

– 7 g/dL

• Vasoactive properties• Oxygen affinity• Dissociation into dimers

Acute Normovolemic Hemodilution

• Conserved RBC Mass• Improved Oxygenation• Preservation of Hemostasis

Other Autologous Transfusions

• Intraoperative blood collection– Cell saver – shed blood

• Postoperative blood collection– Shed blood

Recombinant Factor VIIa

• Approved for hemophilia patients• Enhances thrombin generation on activated

platelets• Cost – exorbitant $15,000.00• Thrombotic complications

DDAVP

• Dose: 0.3 mcg/kg over ½ hour• Release of factor VIII and vWF• Enhances platelet adhesion to the vessel wall• Shortens the prolonged aPTT and bleeding

time

Conclusion• Benefits of transfusion are theoretical• Risks of transfusion are fact• Transfusion of allogeneic blood

represents a major risk for immunosuppression and adverse outcome

• Transfusion must be considered carefully• Accept lower transfusion thresholds• Alternatives to RBC transfusion

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