Update on
Transfusion Practice
Where’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 Landsteiner
1930 Nobel Prize Laureate
• 1900 – Landsteiner
– A-B-O
• 1902– Sturli & DeCastello
– AB
• 1940-Landsteiner
– Rh typing
Lewisohn’s Method of Transfusion
1913
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?
Mean annual # of ABT related deaths from 3 leading causes
Eleftherios et al., 2010
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
Eleftherios et al., 2010
Percent of HTR deaths ABO versus Non-ABO
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 Lesions
Biochemical 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 pO2
Release

Low pH
ATP
Storage Lesions
Biomechanical
•
•
•
•
•
Hemolysis
Membrane area 
Osmotic fragility
RBC adhesion
Deformability 
Storage Lesions
Oxidative
•
•
•
•
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
References
Spiess BD. Blood transfusion: The silent epidemic. Ann Thorac Surg 2001;72:S1832-7.
Gombotz H, Rehak PH, Shander A, Hofman A. Blood use in elective surgery: The Austrian benchmark study.
Transfusion 2007;47:1468-80.
Corwin HL, Carson JL. Blood transfusion-When is more really less? N Engl J Med 2007;356:1667-9.Shander A.
Emerging risks and outcomes of blood transfusion in surgery. Semin Hematol. 2004:41(suppl):117-24.
Brecher ME, Goodnough LT. The rise and fall of preoperative autologous blood donation. Transfusion
2001;41(12):1459-62.
Sugai Y, Sugai K, Fuse A. Current status of bacterial contamination of autologous blood for transfusion. Transfus
Apheresis Sci. 2001;24(3):255-9.
Carson Jl, Duff A, Poses RM, et al. Effect of anaemia and cardiovascular disease on surgical mortality and
morbidity. Lancet 1996;348:1055-60.
Hébert PC, Wells G, Tweeddale M, et al. Does transfusion practice affect mortality in critically ill patients? Am J
Respir Crit Care Med 1997:155:1618-23.
Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA
2002;288(12):1499-1507.
Hébert PC, Wells G, Blajchman MA, et al. A Multicenter, randomized, controlled clinical trial of transfusion
requirements in critical care. N Eng J Med 1999;340(6);409-17.
Ho J, Sibbald WJ, Chin-Yee IH. Effects of strorage on efficacy of red cell transfusion: When is it not safe? Crit Care
Med 2003:31[suppl.]:S687-97.
Opelz G, Sengar DPS, Mickey MR, et al. Effect of blood transfusions on subsequent kidney transplants. Transplan
Proc. 1993;5:253-9.
Blumberg N, Heal JM, Murphy P, et al. Association between transfusion of whole blood and recurrence of cancer.
Br Med J. 1986;293:530-3.
Blumberg N, Heal JM, Chuang C, et al. Further evidence supporting a cause and effect relationship between blood
transfusion and cancer recurrence. Annm Surg. 1988;207:410-5.
Blumberg N, Chuang-Stein C, Heal JM. The relationship of blood transfusion, tumor staging, and cancer recurrence.
Transfusion. 1990;30:291-4.
Vamvakas EC. Possible mechanisms of allogeneic blood transfusion-associated postoperative infection. Trans Med
Rev. 2002;16(2):144-60.
Blumberg N, Heal SM. Universal leukocyte reduction of blood transfusion. Clin Inf Dis. 2007;45:1014-15.
Vamvakas EC, Blajchman MA. Universal WBC reduction: The case for and against. Transfusion 2001;41:691-712.
Capraro L, Kuitunen A, Vento AE, et al. Universal leukocyte reduction of transfused red cells does not provide
benefit to patients undergoing cardiac surgery. J Cardiothor Vas Anes. 2007;21(2):232-6.
Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al. Transfusion related acute lung injury: epidemiology and a
prospective analysis of etiologic factors. Blood 2003;101:454-62.
Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury. Chest 2004;126:249-58.
Kopko PM, Marshall CS, MacKenzie MR, et al. Transfusion-related acute lung injury: report of a clinical look-back
investigation. JAMA 2002;287:1968-71.
Vamvakas EC, Taswell HF. Long-term survival after blood transfusion. Transfusion 1994;34:471-7.
Purdy FR, Tweeddale MG, Merrick PM. Association of mortality with age of blood transfused in septic ICU patients.
Can J Anaesth 1997;44:1256-61.
Moore FA, Moore EE, Sauaia A. Blood transfusion: An independent risk factor for postinjury multiple organ failure.
Arch Surg 1997;132:620-5.
Napolitano LM, Corwin HL. Efficacy of red blood cell transfusion in the critically ill. Crit Care Clin 2004;20:255-68.
Engoren MC, Habib RH, Zacharias A, et al. Effect of blood transfusion on long-term survival after cardiac operation.
Ann Thorac Surg. 2002;74:1180-6.
Corwin HL, Gettinger A, Pearl RG, et al. The CRIT study: Anemia and blood transfusion in the criticallhy ill –
current clinical practice in the United States. Crit Care Med 2004;32(1):39-52.
Suttner S, Piper SN, Kumle B, et al. The influence of allogeneic red blood cell transfusion compared with 100%
oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery. Anesth
Analg 2004;99:2-11.