12Infectious Risk of Transfusion PathogenEstimated Risk Per UnitBacterial contamination1:5 million RBC1:100,000 per apheresis or pooled platelet unitMalaria< 1:1 millionBabesia< 1:1 million regionalChagas DiseaseUnknown presumablyVariant Creutzfeldt-Jacob Disease3 reported case in UK
13Troublesome Events! Alloimmunization (platelets – Leukocytes - RBC) HLA – antigensGranulocyte – platelet – RBC specificAllergic reactionsFebrile reactionsABT – related mortalityTRALI – TAS – HTRs – TTIWhat are the costs of these?
14Mean annual # of ABT related deaths from 3 leading causes Eleftherios et al., 2010
22Oxygen Transports Blood flow - CO Arterial O2 content Transportation DO2 = CO X CaO2TransportationHemoglobinPlasmaDO2 = CO X (%Sat X 1.39 X [Hb])
23Impact of Anemia CRIT NNE Nadir hgb following MI predicts mortality Lowest hct on bypass = increased mortality and incidence of heart failureHowever blood transfusions = increased need for mechanical and inotropic supportNadir hgb following MI predicts mortalityAronson et al. 2007
24Adaption to Anemia Shift in oxyhemoglobin dissociation curve Right - synthesis 2,3-DPGHemodynamic alterationsCOMicrocirculatory alterationsVascular toneRenin-angiotensin-aldosterone system
25Impact of Preop Anemia on Postop Adverse Events Cardiac surgical patients n=5065Low preop hgb = Comorbidities = adverse cardiac eventsAnemia = adverse postop neurologic and renal outcomesKulier et al. 2007Preoperative 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
26Efficacy of RBC transfusion DO2 and utilization = improved outcomesDelivery - Stored RBCLow p50 – shift oxygen dissociation curve – leftDepletion 2,3, DPGDepletion ATPOxygen utilizationOrgan levelHemodynamics and oxygen transport parameters
27Anemia and Transfusion Anemia predicts adverse outcomesCurrent transfusion practice provides no benefit or is harmfulIschemic complications were not decreased with blood transfusionMurphy et al. 2007Patients 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 septicemiaKoch 2007
32Storage Morphologic Biochemical Storage duration Increased mortality Increased length of stay in ICU/HospitalMultiple organ failureTRALIIncreased infectionsImpaired tissue oxygen utilization
33Benefits Hemorrhagic shock Critically ill do not tolerate anemia Goal Increase DO2Increase VO2
34Efficacy of RBC Transfusion in the Critically Ill RBC transfusion did not improve VO2RBC transfusion was not associated with improvements in clinical outcomesRBC transfusion was associated with worse outcomesFactors to identify patients who may benefitLack of efficacy related toAdherence of stored RBCsNitric Oxide bindingDonor leukocytesInflammatory responseDecreased red cell deformability
35Large Randomized Controlled Trials Restrictive strategies vs. liberal strategiesCarson et al. 1996No data demonstrating that allogeneic RBCs increase oxygen carrying capacityHebert et al. 1997Mortality rate was doubled for patients receiving perioperative transfusionEngoren et al. 2002The number of RBC units transfused is an independent predictor of worse clinical outcomeCorwin et al. 2004Corwin et al. 2007
36Transfusion (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 surgeryO2 - not the blood transfusion increased tissue oxygen levelsSuttner et al. (2004) anesth analg 99: 2-11
37Rejuvenation Post-storage metabolic manipulations Mixture of pyruvate – inosine – phosphate – adenineRejuvesol (Cytosol Laboratory Inc)37°C incubation followed by cell washing Restored ATPElevated 2,3-DPG
38Goals Maintenance of high ATP – 2,3, DPG – SNO-hb Reduce hemolysisReduce dead-on-arrival RBCIron toxicityVasoconstriction via NO scavengingMaintain deformability / prevent aggregationPrevent capillary blockageMaintenance of high ATP – 2,3, DPG – SNO-hbMinimize oxidative damagePrevent release, and/or remove bio-active substancesPrevention of TRALILeukoreduction, irradiation, pathogen-reduction, etc.
39Hemoglobin Solutions Limited duration of action Half life minutesHigh colloidal osmotic pressure7 g/dLVasoactive propertiesOxygen affinityDissociation into dimers
40Acute Normovolemic Hemodilution Conserved RBC MassImproved OxygenationPreservation of Hemostasis
42Recombinant Factor VIIa Approved for hemophilia patientsEnhances thrombin generation on activated plateletsCost – exorbitant $15,000.00Thrombotic complications
43DDAVP Dose: 0.3 mcg/kg over ½ hour Release of factor VIII and vWF Enhances platelet adhesion to the vessel wallShortens the prolonged aPTT and bleeding time
44Conclusion Benefits of transfusion are theoretical Risks of transfusion are factTransfusion of allogeneic blood represents a major risk for immunosuppression and adverse outcomeTransfusion must be considered carefullyAccept lower transfusion thresholdsAlternatives to RBC transfusion
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