1. Update on Transfusion Practice Where’s the Evidence?
Connie Lorette Calvin, PhD, CRNA, APRN
Northeastern University

2. History Richard Lower (1631-1691)
Performed the first transfusion (animal to animal) in 1665
Lamb to human 1667

3. 1667 Jean Baptist Denis
Lambs blood
Calves blood

4. 1818 - first human to human transfusion
1774 –
Lavoisier - Role of oxygen in respiration
Priestley – RBC as oxygen carriers
first human to human transfusion
James Blundell

5. Karl Landsteiner 1930 Nobel Prize Laureate
A-B-O
1902– Sturli & DeCastello AB
1940-Landsteiner
Rh typing

6. Lewisohn’s Method of Transfusion Blood is collected in a citrated flask….…...and immediately transfused.

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

8. 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

9. Transfusion Trigger Hemoglobin 10gm/dl Hematocrit 30%
Blood loss of 15% of circulating blood volume
Clinical presentation
Risk:Benefits

10. “Safest Blood” Voluntary blood donation – self exclusion
Surrogate tests
NAT
Does transfusion of banked blood improve outcome for patients?

11. 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

12. 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
Variant Creutzfeldt-Jacob Disease
3 reported case in UK

13. 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?

14. Mean annual # of ABT related deaths from 3 leading causes
Eleftherios et al., 2010

15. 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

16. 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

17. Percent of HTR deaths ABO versus Non-ABO
Eleftherios et al., 2010

18. Transfusion Associated Sepsis
Bacterial contamination
Platelets – highest
Decreased with single-donor
Organisms
Staphylococcus epidermidis
E-coli
Staphylococcus aureus
Bacillus cereus

19. 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

20. Leukocyte Reduction Non-hemolytic transfusion reactions
CMV transmission
HLA alloimmunization
Capraro et al.
Infection rate
90-day mortality
Length of ICU stay

21. Benefits???

22. Oxygen Transports Blood flow - CO Arterial O2 content Transportation
DO2 = CO X CaO2
Transportation
Hemoglobin
Plasma
DO2 = CO X (%Sat X 1.39 X [Hb])

23. Impact of Anemia CRIT NNE Nadir hgb following MI predicts mortality
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

24. Adaption to Anemia Shift in oxyhemoglobin dissociation curve
Right -  synthesis 2,3-DPG
Hemodynamic alterations CO
Microcirculatory alterations
Vascular tone
Renin-angiotensin-aldosterone system

25. 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

26. 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

27. 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

28. Storage Lesions Biochemical Changes
Lactate  = mmol/L
pH  =
2,3-DPG 
ATP 
GSH 
K+ = mEq/L
SNO-Hb 
Ionized Calcium and magnesium = 0
Free Hemoglobin 

29. Regulation of microvascular perfusion mediated by Hemoglobin + NO
Low pO2
Low pH
Release
ATP 

30. Storage Lesions Biomechanical
Hemolysis
Membrane area 
Osmotic fragility
RBC adhesion
Deformability 

31. Storage Lesions Oxidative
Hemoglobin oxidation
Hemoglobin denaturation
Lipid peroxidation
Bioactive Substance
Cytokines
Histamines
Lipids
Soluble HLA

32. Storage Morphologic Biochemical Storage duration Increased mortality
Increased length of stay in ICU/Hospital
Multiple organ failure
TRALI
Increased infections
Impaired tissue oxygen utilization

33. Benefits Hemorrhagic shock Critically ill do not tolerate anemia Goal
Increase DO2
Increase VO2

34. 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

35. 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

36. 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

37. 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

38. Goals Maintenance of high ATP – 2,3, DPG – SNO-hb
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.

39. Hemoglobin Solutions Limited duration of action
Half life minutes
High colloidal osmotic pressure
7 g/dL
Vasoactive properties
Oxygen affinity
Dissociation into dimers

40. Acute Normovolemic Hemodilution
Conserved RBC Mass
Improved Oxygenation
Preservation of Hemostasis

41. Other Autologous Transfusions
Intraoperative blood collection
Cell saver – shed blood
Postoperative blood collection
Shed blood

42. Recombinant Factor VIIa
Approved for hemophilia patients
Enhances thrombin generation on activated platelets
Cost – exorbitant $15,000.00
Thrombotic complications

43. 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

44. 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

45. References
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46. Vamvakas EC. Possible mechanisms of allogeneic blood transfusion-associated postoperative infection. Trans Med Rev. 2002;16(2):
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