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

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Presentation on theme: "Update on Transfusion Practice Wheres the Evidence? Connie Lorette Calvin, PhD, CRNA, APRN Northeastern University."— Presentation transcript:

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

2 History Richard Lower ( ) –Performed the first transfusion (animal to animal) in 1665 –Lamb to human 1667

3 1667 Jean Baptist Denis –Lambs blood –Calves blood

4 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 1900 – Landsteiner –A-B-O 1902– Sturli & DeCastello –AB 1940-Landsteiner –Rh typing

6 Lewisohns Method of Transfusion 1913 Blood is collected in a citrated flask….…...and immediately transfused.

7 Enculturation of Transfusion Blood is a life giving force save a life

8 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 PathogenEstimate Risk Per Unit Hepatitis AUnknown - <1:1million Hepatitis B1 : 277,000 Hepatitis C1 : 1,930,000 HIV - 11 : 2,135,000 HTLV -I, II1 : 2,993,000 CMVInfrequent in leukocyte reduced components West Nile1 : 350,000

12 Infectious Risk of Transfusion PathogenEstimated Risk Per Unit Bacterial contamination1:5 million RBC 1:100,000 per apheresis or pooled platelet unit Malaria< 1:1 million Babesia< 1:1 million regional Chagas DiseaseUnknown presumably < 1:1 million 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 Jk b, Jk a, Kell, Fy a, Fy b, E, Js a, 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 –DO2 = CO X CaO2 Transportation –Hemoglobin –Plasma –DO2 = CO X (%Sat X 1.39 X [Hb])

23 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

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 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 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 = ,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 No data demonstrating that allogeneic RBCs increase oxygen carrying capacity –Hebert et al Mortality rate was doubled for patients receiving perioperative transfusion –Engoren et al The number of RBC units transfused is an independent predictor of worse clinical outcome –Corwin et al –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 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, 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 Spiess BD. Blood transfusion: The silent epidemic. Ann Thorac Surg 2001;72:S Gombotz H, Rehak PH, Shander A, Hofman A. Blood use in elective surgery: The Austrian benchmark study. Transfusion 2007;47: Corwin HL, Carson JL. Blood transfusion-When is more really less? N Engl J Med 2007;356: Shander A. Emerging risks and outcomes of blood transfusion in surgery. Semin Hematol. 2004:41(suppl): Brecher ME, Goodnough LT. The rise and fall of preoperative autologous blood donation. Transfusion 2001;41(12): Sugai Y, Sugai K, Fuse A. Current status of bacterial contamination of autologous blood for transfusion. Transfus Apheresis Sci. 2001;24(3): Carson Jl, Duff A, Poses RM, et al. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996;348: 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: Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA 2002;288(12): 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); 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.]:S Opelz G, Sengar DPS, Mickey MR, et al. Effect of blood transfusions on subsequent kidney transplants. Transplan Proc. 1993;5: Blumberg N, Heal JM, Murphy P, et al. Association between transfusion of whole blood and recurrence of cancer. Br Med J. 1986;293: 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: Blumberg N, Chuang-Stein C, Heal JM. The relationship of blood transfusion, tumor staging, and cancer recurrence. Transfusion. 1990;30:291-4.

46 Vamvakas EC. Possible mechanisms of allogeneic blood transfusion-associated postoperative infection. Trans Med Rev. 2002;16(2): Blumberg N, Heal SM. Universal leukocyte reduction of blood transfusion. Clin Inf Dis. 2007;45: Vamvakas EC, Blajchman MA. Universal WBC reduction: The case for and against. Transfusion 2001;41: 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): Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al. Transfusion related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood 2003;101: Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury. Chest 2004;126: Kopko PM, Marshall CS, MacKenzie MR, et al. Transfusion-related acute lung injury: report of a clinical look-back investigation. JAMA 2002;287: Vamvakas EC, Taswell HF. Long-term survival after blood transfusion. Transfusion 1994;34: Purdy FR, Tweeddale MG, Merrick PM. Association of mortality with age of blood transfused in septic ICU patients. Can J Anaesth 1997;44: Moore FA, Moore EE, Sauaia A. Blood transfusion: An independent risk factor for postinjury multiple organ failure. Arch Surg 1997;132: Napolitano LM, Corwin HL. Efficacy of red blood cell transfusion in the critically ill. Crit Care Clin 2004;20: Engoren MC, Habib RH, Zacharias A, et al. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg. 2002;74: 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): 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.

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