HAI Berlin Can we still afford blood transfusion? Transfusion Economics Prof. Dr. med. Thomas Frietsch, G (EBS) Klinik fr Ansthesie und Intensivtherapie Universittsklinikum Giessen Marburg GmbH, Philipps Universitt Marburg HAI Berlin Agenda - of a potentially more boring talk you thought it would be Principles of pharmacoeconomic evaluations (Drummond 1997) Kind of Blood Transfusion Cost of Blood Transfusion Effects of Blood Transfusion Efficacy of Blood Transfusion Efficiency of Blood Transfusion Benefits of Blood Transfusion Risks of Blood Transfusion Economics of Blood Transfusion Transfusion / Health economics is ---- NOT minimizing expenditures BUT maximizing effectiveness per unit of cost to GET THE MOST BANG FOR THE BUCK HAI Berlin Economics in Health Care - definitions and methods Dealing with efficacy, cost effectiveness, cost benefit, cost utility Types of pharmacoeconomic evaluations cost-minimization analysis (CMA) cost-effectiveness analysis (CEA) cost-utility analysis (CUA) cost-benefit analysis (CBA) ICER QALY / Program Profit Users' Guides to the Medical Literature: XIII. How to Use an Article on Economic Analysis of Clinical Practice: A. Are the Results of the Study Valid? Drummond, Michael; Richardson, W; OBrien, Bernie; Levine, Mitchell; Heyland, Daren JAMA. 277(19): , May 21, 1997. HAI Berlin Economics in Health Care - and in detailed surview HAI Berlin Economics in Transfusion Medicine - Examples CEA Transmission of HIV, Hep B/C to 9.75 mio US $/QALY ICER HIV antibody screening in the US $ 3600/QALY HIV nucleid acid testing NAT> $ 2 mio/QALY HCV NAT$ 1.8 mio/QALY HBsAG+anti HBc$ 1 mio/QALY HBV NAT$ 66 mio/QALY West Nile NAT(June-Nov/whole year)$ 0.3/0.5 mio/QALY H1N1? Donor selection? Mistransfusion (mechanical barrier)$ /QALY TRALI$ to /QALY Sepsis$ /QALY Custer B & Hoch JS. Cost-Effectiveness Analysis: What it really means for transfusion medicine decision making. Transfus Med Rev 2009; 23: 1-12 HAI Berlin Surview of Affordability: General Approach Allogeneic Red White Platelets Coags) Autologous Normovolemic Hemodilution Predonation Cell Salvage Avoidance Strategies Algorithms and Shresholds Controlled Hypotension Blood Substitutes Point of Care Testing Patient Blood Management HAI Berlin Cost of blood transfusion HAI Berlin Detailled Agenda - of a potentially more boring talk you thought it would be Principles of pharmacoeconomic evaluations (Drummond 1997) Effect of Blood Transfusion Cost and efficacy of oxygenation therapy Hospital economic perspectives of oxygenation therapy Cost and Efficacy of Coagulation Therapy Hospital economic perspectives of coagulation therapy Solution : hospital fitted concepts HAI Berlin Blood transfusion : Effects 1 Transfusion volume in the US/D each year: 29/4 mio units (14.2 mio PRBC, 5.5 mio FFP (2005-6)) > 125 transfusion related fatalities > 64 TRALI 1: 9 AB0 incompatibility 1: (FDA) incompatibility general < 1: (estimate) fatal septic transfusion reaction 1: 2 ARDS OR 1.06 (CI ) 2 In ICU/ventilated pats.: length of stay by6.3 days (CI ) mortalityby21% (OR 1.21, CI 1.00 1.48) cost by US $ (CI ) 1 Solheim BG. Indications for use and cost-effectiveness of pathogen reduced AB0-universal plasma. Curr Opin Hematol 2008; 15: Chaiwat O, et al. Early Packed Red Blood Cell Transfusion and ARDS after Trauma. Anesthesiology 2009; 110: Zilberberg MD et al. Anemia, transfusions and hospital outcomes among critically ill. Critical Care 2008; 12: R60 (n=4400, retrospective, mv > 96h) HAI Berlin Cost of blood transfusion Fix and variable cost Basha et al. Transfusions And Their Costs: Managing Patients Needs And Hospitals Economics. Int J Emer Int Care Med 2009 HAI Berlin UNITacquisitioncost PRBC, non leuko-depleted $154 > 300 / US$ 400 = hospital costs for the unit ( 150), storage, cross match, labelling, processing etc. administration and production (donor testing 35, donor fee 5-80, transport, cooling, centrifugation, baging and storage until delivery of blood products), if possible detrimental outcomes are accounted US$1600 to $2400 fresh frozen plasma (FFP)$ 51 80 / US$ 100 platelets (pooled or apheresis)$ 461 450 / US$ 600 Prothrombin complex / Cryoprecipitate 800 / US $ 750 2,4 mg FVIIa (Eptacog alfa) 2600 / US$ 2500 600 IU/ kg rhEpo (30 000IU) 570 / US$ 420 Custer B & Hoch JS. Cost-Effectiveness Analysis: What it really means for transfusion medicine decision making. Transfus Med Rev 2009; 23: 1-12 Cost of blood transfusion HAI Berlin Davies L et al. Cost Minimization Analysis of preoperative Erythropoietin vs. Autologous and Allogeneic Blood Donation in Total Joint Arthroplasty. J Arthroplasty 2008; in press Analysis of various methods-CMA 1)68 RCTS: Carless P, Moxey A, O'Connell D, Henry D: Autologous transfusion techniques: a systematic review of their efficacy. Transfus Med 14: , ) Davies et al.: Cost effectiveness of cell salvage and other methods of minimizing allogenic blood transfusion: a systematic review and ecomomic mode. HTA 44:1-229, )7-10 g/dl, most 8-9 g/dl: Carson JL, Hill S, Carless P, Hbert P, Henry D: Transfusion triggers: a systematic review of the literature. Transfus Med Rev 16:187-99, 2002 HAI Berlin Effect of alternatives to allogeneic transfusion Davies L et al. Cost-effectiveness of cell salvage and alternative methods. Health Technol Assess 2006; 10: 44 n.s. effect HAI Berlin How precise a CEA has to be Sonnenberg A et al. The cost-effectiveness of autologous transfusion revisited. Anesthesiology 1999; 39:811 HAI Berlin Background: Autologous techniques too expensive - avoidance of postoperative infections not considered Methods: CUA: Markov cohort analysis, hip replacement, cost per QALY Assumption: serious infection in 3.7% of cases US $ addit. costs Results: RR > 2.4 autologous is dominant lower costs at RR 3.7, cost effectiveness $/QALY 2,4 > RR > 1.1 cost effectiveness < $/QALY 1,1 > RR > 0 cost effectiveness up to 3,400,000 $/QALY Conclusion: Cost effectiveness dependent on risk of bacterial infection Alternatives : Autologous Predonation / Cell Salvage HAI Berlin PAD vs. EPO vs. Combination HAI Berlin Another not calculated aspect Immunosuppression and cancer recurrence HAI Berlin CMACEA/CUA /patICER/QALY Red blood cell transfusion/alternatives Elective surgery Allogeneic Red PRBC Avoidance of Allogeneic T. Autologous Hemodilution (ANH) Predonation (PAD) Cell Salvage (CS) Avoidance Strategies Restrictive Shreshold Controlled Hypotension Blood Substitutes/ EPO Point of Care Testing Patient Blood Management below the Hb content of 8g/L 1500** RR 0.59 (CI 0.27 0.52) Davies L et al. Cost-effectiveness of cell salvage and alternative methods. Health Technol Assess 2006; 10: 44 *Mirzy et al. Efficacy and economics of postop. CS for elective total hip replacement. Ann R Coll Surg Engl 2007; 89: 777 ** Green et al. Cost Minimization Analysis of Preoperative Erythropoietin.. J Arthroplasty 2009, epub ***Martinez et al. Transfusion strategy for primary knee and hip arthroplasty. BJA; 2007; 99: ****OKeeffe et al. A massive transfusion protocol to decrease blood component use and costs. Arch Surg 2008; 143: $ Mio RR 0,58 ( ) n.d. n.s. RR 0.69 n.s. RR 0.36 (.25 .51) RR 0.49 (.38 .64) $ $ 2580 $ 5.7 mio $ 7.7 mio 300* 32*** *,** *, **** 300* ** n.d. HAI Berlin How to perform PAD- Impact on efficacy Goodnough et al. Preoperative red cell production in patients undergoing aggressive autologous blood phlebotomy with and without erythropoietin therapy. Transfusion Jun;32(5): Goodnough et al. The effect of patient size and dose of recombinant human erythropoietin therapy on red blood cell volume expansion in autologous blood donors for elective orthopedic operation. J Am Coll Surg Aug;179(2):171-6 Wittig et al. Short donation intervals in preoperative autologous blood donation in the concept of autologous transfusion. Anaesthesist Jan;43(1):9-15. Singbartl et al. Preoperative autologous blood donation - part II. Adapting the predeposit concept to the physiological basics of erythropoiesis improves its efficacy. Minerva Anestesiol Mar;73(3): HAI Berlin Avoidance Strategies: Cell Salvage 1 CEA in lumbar fusion: 225 per patient: Unit PRBC 450 vs unit CS 370 Costs with CS 995 447 / pat. vs w/o CS 1220 269 (P < 0.05). 2 CBA in lumbar fusion: PAD no allogeneic blood, 20% w/o PAD + w/o CS vs 24% w/o PAD with CS 1 Savvidou C. et al. Efficacy and cost-effectiveness of cell saving blood autotransfusion in adult lumbar fusion. Transfus Med 2009; 19: Reitmann CA et al. The Cell Saver in Adult Lumbar Fusion Surgery. Spine 2004;29:1580-4 HAI Berlin Business economics : Recalculate your ressources *) Cost analysis: Klinikum Mannheim 2004 **) Leukocyte depletion does not improve outcome: Frietsch T, Karger R, Schler M, Huber D, Bruckner T, Kretschmer V, Schmidt S, Leidinger W, Weiler-Lorentz A: Leukodepletion of autologous whole blood has no impact on perioperative infection rate and length of hospital stay. Transfusion 2008 Oct;48(10): Identify the dominant strategy Efficacy : Avoidance allog. transfusion Costs*) Knee arthoplastyPAD >CS 2 units PAD >CS 340,63 > 236,95 Hip arthoplastyPAD > > CS 3 units 2,6 %>>42,7 % 2 units 4,4 % 2 units < CS 3 units > CS 3 PAD 441,86 2 PAD 362,62 / 395 HAI Berlin Alternative decisions : Example- PAD vs CS *) Cost analysis: Klinikum Mannheim 2002 Production PAD /h time/donor= staff cost Physician / h 50,08 Nurse / h 25,61 x 0,52 x 0,96 26,04 24,59 Personnel Cost 50,63 Personnel Total PAD Costs EntryAmount Personnel cost Material/Disposables Machine maintenance expensemaintenanceexpense Laboratory Room rent 50,63 39,31 3,93 70,57 1,10 Sum Retransfusion 165,54 + 7,88 HAI Berlin Avoidance Strategies: Algorithms 1 Retrospective CMA: Reduction of turnaround time from 40 to 10 (20) min 2 270 US$ per patient, US$ per y 1 OKeeffe et al. A massive transfusion protocol to decrease blood component use and costs. Arch Surg 2008; 143: Martinez V et al. Transfusion strategy for primary knee and hip arthroplasty. BJA 2007; 99: Hebert et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340: Conclusion for the Cost-efficiency of Oxygenation therapy: It depends: on risk profile of the patient on the surgical procedure your country (pay scale, ethical opinions, etc.) your institution available strategies budget range personnel ... .. . HAI Berlin Coagulation Therapy: plasma or factor substitution, haemostatic agents POCT: see avoidance strategies Algorithms: see avoidance strategies Plasma (FFP): efficacy low, high volume needed, all factors included, not standardized Lyophilized Plasma: same, only volume to substitution ratio improved ABO-universal plasma: not approved yet (Solheim et al Current Opin Hematol 2008) Platelets: Vitamin K: PPSB/prothrombin complex: Cryoprecipitate: Fibrinogen: Recombinant F VIIa: F XIII: Antifibrinolytics: Aprotinin, Tranexamic acid, Aminocapron acid DDAVP/Desmopressin: HAI Berlin Coagulation Therapy: Plasma Indication: Treatment and prophylaxis of complex coagulopathy due to acquired (perioperative) loss, Isolated factor deficiency w/o the availability of special concentrate preperations ( FV, FXI oder VWF:CP(ADAMTS13)). Dose: quick mL/min admin. of 15-20mL/kg if no lab, 1mL/kg for 1% increase in Quick Aim at stop of oozing or Quick > 50, Fibrinogen > 1, APTT < 45 s Efficacy: Bundesrztekammer. German Cross sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. 4th ed. Dtsch Arztebl 2008; 105: A Continued Blood loss > 100mL/min after 4 to 6 (up to 10 PRBC, if no coag lab avail.) Clinical, (lab not available)1C Continued or assumed blood loss together with Quick 45 s and or Fibrinogen < 1g/L (Clauss) 1C NOT INDICATED: prophylactic following pump period without coagulopathy Even if Quick is < 50% or Fibrinogen < 1g/L 1A HAI Berlin Coagulation Therapy: Platelets Indication: prophylaxis of DIC (WHO IV 2c) below /L treatment of bleeding episodes below /L(WHO III 2c) Efficacy: Bundesrztekammer. German Cross sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. 4th ed. Dtsch Arztebl 2008; 105: A Minor surgery< 20000/l2C Major surgery< 50000/l2C Neurosurgical and ophtalmological surgery< /l1C Cardiac surgery after pump period< 20000/l2C Epidural- / Spinal Anesthesia< 80000/l / < 50000/l1C HAI Berlin Coagulation Therapy: Factor VIIa Indication: Inherited (hemophilia), acquired (perioperative) deficiency, Glanzman thrombasthenia (refract. Platelets (EU)) Prophylaxis & treatment of bleeding episodes Efficacy: OR 0.29 (CI ), > 50g/kg OR 0.49 ( ) for reduction of allogeneic units CBA: preconsiderations: dose 90g/kg cost 5000 /8000 US $ (2008) Cost of a PRBC 250 / 350 US$ No benefit in ICU stay, LOS, mortality No thromboembolic complications Cost-benefit ratio beneficial (RR> 0.5) only if a patient > 40 PRBCs Rannucci, M et al. Efficacy and Safety of Recombinant Avctivated Factor VII in Major Surgical Procedures. Arch Surg 2008; 143: HAI Berlin Coagulation Therapy: Desmopressin, DDAVP Indication: Mild hemophilia, von Willebrands disease, acquired (perioperative) platelet dysfunction or deficiency, Efficacy: 1 single dose 0.3g/kg reduces transfusion requirements by 0.29 ( ) units per pat (80 mL), more in non-cardiac surgery. Safety: 5 mild hypotension (8.4% vs 2.1%, p postop CS Recalculate the use of EPO (on the base of new cost analyses) Modified from Davies L et al. Cost-effectiveness of cell salvage and alternative methods. Health Technol Assess 2006; 10: 44 HAI Berlin The better and better affordable solution : Patient Blood Management 3 main elements: (1) correction of a low preoperative erythrocyte mass or preoperative anemia, (2) minimizing peri- operative erythrocyte loss (3) using minimal (i.e., low) hemoglobin- based transfusion triggers. Goodnough & Shander. Blood Management. Archives of Pathology and Laboratory Medicine: Vol. 131, No. 5, pp. 695701. Spahn D et al. Patient Blood Management: The Pragmatic Solution for the Problems with Blood Transfusions Anesthesiology 2008; 109: 951-3 HAI Berlin The Toolbox: Patient Blood Management further elements (EVIDENCE BASED): Implement a transfusion protocol- PATIENT BLOOD MANAGEMENT SOP for most of procedures Involve surgeons, hemastesiologist, transfusion medicine Determination of the exposure risk to allogeneic transfusion Low preoperative red cell mass High blood loss (Procedure/Surgeon specific) Identify and correct coagulation disorder Increase low red cell mass Iron and EPO PAD ANH Decrease perioperative blood loss Blood sparing surgical techniques Low/restrictive transfusion triggers POCT-based algorithm Avoid hypothermia CS Antifibrinolytics, Fibrinogen and F XIII Renew your circuit techniques (i.e. match oxygenator size, vacuum assisted venous return, reduce prime volume, full biocompatibility....) Controlled hypotension Incorporate blood unit quality analysis (age and cross match) Mannheimer Transfusionsgesprche der IAKH e.V. 27/28.Feb Arbeitskreis der DIVI Hmotherapie in Zusammenarbeit mit der Interdisziplinren Arbeitsgemeinschaft fr Klinische Hmotherapie (IAKH) IAG Klinische Hmotherapie der DIVI Fehlerregister der IAKH national CIRS for Transfusion IncidentsAmong Topics: Submeeting of Quality Control Managers Patient Blood Management2010 HAI Berlin Allogeneic Blood Transfusion in the view of a viral pandemia Decision tree analysis HAI Berlin The Markov Model Favourable over decision tree when Probabilities of alternatives are not enough, time points or periods of medical states or events after the decision are important Markov Model characteristics: Finite number of health states in which identical patients can be Time cycles of same sizes Transition from on to another cycle at a distinct probability Transition probabilities solely dependent from actual health condition Accounting for acute medical events during and subsequent hospital stay Here basic choice: probability of autologous donation and transfusion, allogeneic transfusion Acute events: transfusion and related complications, infections, mortality Subsequent: hepatitis, HIV, cancer, a.s.o. Markov Chain: same transition probabilities Markov process: transition probabilities vary with time Cohort Simulation: cohort runs various cycles creating a table column (which part of cohort is in which cycle) production of cumulating incidence of medical events, life span, costs etc. HealthyHep. C Cirrhosis Carcinoma Death 0,04 0,6 0,5 0,001 0,9 0, ,7 0,0001 0,11 Allogeneic Transfusion during Hip Surgery Adapted from Siebert, U. Transparente Entscheidungen in Public Health mittels Systemat. Entscheidungs- analyse. In: Schwartz, F.W. 2.ed. Das Public Health Buch. Elsevier, Mnchen, 2002, 932 S HAI Berlin Point Checklist according to Drummond 1.Q: Was a well-defined question posed in answerable form? A: Yes; allogeneic safety increase why then costs for autologous? Increased risk for infections associated to allogeneic transfusion have impact on cost effectiveness? alternatives clear, both costs and effects considered-defined as dominance, viewpoint relevant for decision making 2.Q: Was a comprehensive description of the competing alternatives given? A: Autologous versus Allogeneic description not necessary (practice Mayo Clinic n = 332), do-nothing alternative is not considered (tolerance of low hemoglobin levels risk of transfusion in elective hip surgery , infection induction effect , statistical power?) 3.Q: Was the effectiveness of the programs or services established? A: not always RCTs, simulation CU Model/Decision Maker, Data: empirical, given sources (studies, NIH, Heiss, Record review New Jersey Hospitals), assumptions used, a range of risks with various effectiveness given 4.Q: Were all the important and relevant costs and consequences for each alternative identified? A: Previous assumptions of calculated models adopted, only one view point - third party payer (insurance), operating and capital costs from a single publication (table 2) HAI Berlin Background: Autologous techniques too expensive - avoidance of postoperative infections not considered Methods: CUA: Markov cohort analysis, hip replacement, cost per QALY Assumption: serious infection in 3.7% of cases US $ addit. costs Results: RR > 2.4 autologous is dominant lower costs at RR 3.7, cost effectiveness $/QALY 2,4 > RR > 1.1 cost effectiveness < $/QALY 1,1 > RR > 0 cost effectiveness up to 3,400,000 $/QALY Conclusion : Cost effectiveness dependent on risk of bacterial infection HAI Berlin Explanation of used analysis: The Markov Model Favourable over decision tree when Probabilities of alternatives are not enough, time points or periods of medical states or events after the decision are important Markov Model characteristics: Finite number of health states in which identical patients can be Time cycles of same sizes Transition from on to another cycle at a distinct probability Transition probabilities solely dependent from actual health condition Accounting for acute medical events during and subsequent hospital stay Here basic choice: probability of autologous donation and transfusion, allogeneic transfusion Acute events: transfusion and related complications, infections, mortality Subsequent: hepatitis, HIV, cancer, a.s.o. Markov Chain: same transition probabilities Markov process: transition probabilities vary with time Cohort Simulation: cohort runs various cycles creating a table column (which part of cohort is in which cycle) production of cumulating incidence of medical events, life span, costs etc. HealthyHep. C Cirrhosis Carcinoma Death 0,04 0,6 0,5 0,001 0,9 0, ,7 0,0001 0,11 Allogeneic Transfusion during Hip Surgery Adapted from Siebert, U. Transparente Entscheidungen in Public Health mittels Systemat. Entscheidungs- analyse. In: Schwartz, F.W. 2.ed. Das Public Health Buch. Elsevier, Mnchen, 2002, 932 S HAI Berlin Avoidance Strategies: Rules based on evidence Prospective Trial: Hebert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340: Efficacy of a restrictive strategy 8g/l vs liberate 10g/l hemoglobin HAI Berlin Clinical Study 2 10 Point - Checklist 1.Q: Was a well-defined question posed in answerable form? 2.A: Yes; allogeneic safety increase why then costs for autologous? Increased risk for infections associated to allogeneic transfusion have impact on cost effectiveness? 3. alternatives clear, both costs and effects considered-defined as dominance, viewpoint relevant for decision making 4.2.Q: Was a comprehensive description of the competing alternatives given? 5.A: Autologous versus Allogeneic 6.description not necessary (practice Mayo Clinic n = 332), do-nothing alternative is not considered (tolerance of low hemoglobin levels risk of transfusion in elective hip surgery , infection induction effect , statistical power?) 3.Q: Was the effectiveness of the programs or services established? 4.A: not always RCTs, simulation CU Model/Decision Maker, Data: empirical, given sources (studies, NIH, Heiss, Record review New Jersey Hospitals), assumptions used, a range of risks with various effectiveness given 4.Q: Were all the important and relevant costs and consequences for each alternative identified? A: Previous assumptions of calculated models adopted, only one view point - third party payer (insurance), operating and capital costs from a single publication (table 2) HAI Berlin Clinical Study 2 10 Point - Checklist HAI Berlin Clinical Study 2 10 Point - Checklist 5.Q: Were costs/consequences measured accurately in appropriate physical units? 6.A: 1997 $, QALYs, some estimates, omitted were severe transfusion reactions 7.(too rare), administration of wrong blood (equal for both), discarded blood 6.Q: Were costs and consequences valued credibly? 7.A: yes, sources and methods of valuation mentioned 7.Q: Were costs and consequences adjusted for differential timing? 8.A: equal for both alternatives, 1997 $, adjusted to medical care component of the Consumers Price Index, future costs and life expectancies with annual discount rate 3%, plus excess mortality from HIV, Cancer a.s.o., no discount factor applied, QAL weights-utilities from most recent literature 8.Q: Was an incremental analysis of costs/consequences of alternatives performed? 9.A: yes, two way sensitivity analysis identifies the costeffectiveness threshold above autologous transfusion is dominant dependent on risk versus cost of infection Bnm, HAI Berlin Clinical Study 2 10 Point - Checklist 9Q: Was allowance made for uncertainty in the estimates of costs/consequences? 10A: Yes, the Markov model is a cohort simulation with a finite n of health states, transition rate 10Q: Did the presentation of study results include all issues of concern to users? A: Almost, but - Postop. Bacterial infection rate 0.37% age of base case model ok for 1999, but too young, now rising> 65y no sex difference (Blood loss and transfusion rates difference) exclusion of transfusion reactions and blood erroneous administration rate of transfusion from only 332 pat in US, 89% transfusion rate TR too high 2.4 units AT, 1.1 U addit. AAT in 36% American vs German morbidity & mortality from elective hip surgery i.e. 1.1% mortality, 1,6% TR = 56% AAT < 5% mortality 0% HAI Berlin Results of the assessment study 2 - Conclusion - Study designwell but data base poor Methods Markov condition Estimates, assumptions not always given, o.k., some flaws Some assumptions underlying the simulation probably incorrect Some facts should have not been omitted/ depend on local conditions Transfer to local or European conditions and future -10 years later difficult, impossible Factors hard to consider-peace of mind, preop. health improvement now to be considered Interpretation: ...correct In total Reconsideration of an underestimated but probably better therapy by inclusion of new evidence of side effects of the standard of care therapy so far. Actual and corrected results even more in favour of autologous transfusion. HAI Berlin Comparison Allogeneic vs. autologous transfusion