10/10/2018. Whole Blood vs. Component Prime Therapy in Neonatal & Pediatric CPB. Disclosure. Objectives. Historical Perspective

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1 Disclosure Whole Blood vs. Component Prime Therapy in Neonatal & Pediatric CPB Thomas M. Klein, BS, CCP, FPP Department of Cardiovascular Perfusion Division of Cardiothoracic Surgery Cincinnati Children s Hospital Medical Center Thomas.Klein@ccmhc.org Objectives Historical Perspective Review prime and patient management challenges for neonatal CPB Discuss outcomes associated with FWB vs. RBC/FFP component priming strategies Preliminary data from the 2017 Groom International Pediatric Perfusion Survey Discuss optimal priming strategies and interventions to reduce CPB-related morbidities Cardiopulmonary Bypass Principles and Practice: Gravlee, Stammers, Ungerleider Perfusion started out with primes of: Normal composition (whole blood) Normal flows (70-80 ml/kg/min) Normal blood pressures Hypothermia was used to protect organs from adverse effects of: Low flow hemodilution Around 1960 surgeons began using crystalloid solutions or plasma-expanding colloids to reduce or eliminate blood from prime 1

2 Neonatal Challenges Neonatal Challenges M&M during neonatal heart surgery has dramatically improved over the past decade; however it remains higher than in older children and adults. Ann Thorac Surg 1 Neonates endure the equivalent of a complete exchange transfusion or more despite attempts to miniaturize ECC s NEJM 3-6 Increased bleeding and allogeneic transfusion requirements vary inversely with the age and size of infants requiring cardiac surgery Ann Thorac Surg 8, 20 Exaggerated dilutional disruptions of coagulation ATS 1-3 Coagulation disturbances leading to postop bleeding in neonates are multifactorial: Ann Thorac Surg % of neonates undergoing CPB had factor levels significantly less than normal, due to immature hepatic system that continues to mature throughout first 2-3 weeks of life (1992 ATS 13,14) Hemodilution: Clinically significant thrombocytopenia (70-80% decrease from baseline) 28 Systemic Inflammation Prolonged bypass times Use of DHCA These insults contribute to: NEJM 1,2,9,10 Capillary leak syndrome Generalized edema Myocardial injury Multisystem organ failure Balanced Physiologic Prime Whole Blood vs. PRBC Rationale The prime is the largest volume of fluid administered to the patient during surgery, and is given instantaneously, unlike other perioperative fluids The prime can be a significant determinant in the patient s metabolic response to the cardiac operation due to: 20 Prime composition Disparity in size between the prime and patient CBV Deleterious effects of CPB being more pronounced due to immature tissue and organ function FWB Proponents: Lessen severity of coagulopathy and inflammation NEJM 2004; 11,12 Reduce overall donor exposure Improved postop hemostasis Disadvantages of using FWB: Difficulties with procurement Expedited testing required Loss of component inventory in blood bank 2

3 Whole Blood vs. PRBC Transfusion Studies document the detrimental effects of stored RBC s contributing to severe complications: 33 High levels of activated inflammatory cells Acid-base Hyperglycemia Electrolyte imbalances Although PRBC s are the most non-physiologic, FWB is not without derangements: 20 NEJM 2004; 351: Children s Medical Center, Dallas TX Single-center, randomized, double-blind, controlled trial Prime component description: FWB: 1/2 in prime, 1/2 during rewarming ( 48 hrs stored at 2-6 o C) n=96; median age = 47.6 hrs Reconstituted blood (50% PRBC stored at 1-6 o C & 50% FFP) n=104; median age = hrs (<5 days) 200 infants < 1 year were included: Clinical outcomes and serologic measures of SIRS and myocardial injury were compared Only patients utilizing a blood prime and a specific surgical team were eligible Strict clinical guidelines for postop transfusion were instituted to allow comparison of bloodtransfusion requirements between groups Intraop & Postop Outcomes N Engl J Med 2004; 351: MouS, Giroir B, et al Primary Outcome Variables Survival and ICU Length-of-Stay in ICU, up to 7 days No significant differences between groups in: Intraoperative variables Transfusion requirements Rate of death from all causes Frequency of severe postop clinical course Delayed sternal closure Need for ECMO support Overall number of postop complications No significant differences between primary outcome variables The reconstituted blood group trended (P=0.10) toward a lower median score than the fresh WB group NOTE: Post hoc subgroup analyses to include days spent in ICU to postop day 28 including examination of cohorts with single-ventricle lesions, cohorts with two-ventricle lesions, and cohorts grouped according to age ( 28 days [neonates] or > 28 days [infants]) failed to reveal significant differences in outcomes between patients who received fresh WB and those who received reconstituted blood. 3

4 Clinical Outcomes Clinical Variables: ICU Length-of-Stay, Cumulative Fluid Balance Clinical Outcomes Clinical Variables: Duration of Mechanical Ventilation Differences in other clinical variables proved to be significant ICU LOS significantly shorter for PRBC Cumulative fluid balance significantly smaller at 48 hours and trend toward less edema throughout the 72-hour period Mechanical ventilation in PRBC group trended toward shorter duration The following parameters were similar in both groups: Early postop chest-tube output Blood-product transfusion requirements Levels of serum mediators of inflammation Cardiac Troponin I Perioperative inotropic support Myocardial injury SIRS Donor exposure in reconstituted-blood group was greater than the FWB group (4.0 donors vs. 3.5 donors, P = 0.05) Due to obligate use of two donors for blood reconstitution, as opposed to a single donor for FWB COST CONCLUSION Additional charge of $110 for RWB Extended stay in ICU associated with FWB = $5, and doesn t include charges for medications and other therapies associated with prolonged intensive care Approximately 20,000 CHD operations performed annually in US, the cost savings could be substantial 23 The use of FWB for CPB priming has no advantage over the use of a combination of PRBC and FFP during CHD surgery Moreover, circuit priming with FWB is associated with: an increased LOS in the ICU (70.5 hrs vs hrs, P=0.04) increased perioperative fluid overload (-6.9 ml/kg vs ml/kg P=0.003) FWB trended toward an increased duration of mechanical ventilation (P=0.09) 4

5 JECT 2007; 39: Children s Hospital Illinois JECT 2007; 39: Children s Hospital Illinois Retrospective evaluation 100 patients to analyze if there were benefits to their FWB and Pre-BUF primes on outcomes in neonatal & pediatric cardiac surgery 3 groups all Pre-BUF: FWB vs. PRBC prime < 5 kg FWB vs. < 5 kg PRBC prime 5+ kg FWB vs. 5+ kg PRBC prime Results: Perioperative inotrope and post op blood loss did not differ among groups No statistical differences between following outcomes: Intra-op death Intra-op extubation Delayed sternal closure Mediastinal reexploration JECT 2007; 39: Children s Hospital Illinois Ped Anes : Children s Hospital Boston Harvard Medical School RESULTS: FWB leads to significantly less blood exposure, specifically in the <5kg population No differences in postop blood loss between FWB or PRBC CUMULATIVE BLOOD EXPOSURE (periop and ICU for first 12 hrs): 11 62% of >5 kg FWB group received 1 blood exposure (P <.0001) vs. 18% of PRBC group 64% of PRBC group received >/= 3 exposures (P <.0003) vs. 28% FWB group 85% of <5 kg PRBC prime received > 3 exposures (P <.0001) Prospective observational study Authors hypothesized in neonates and infants, a small volume CPB prime consisting of either reconstituted WB (RWB) or non-fresh WB (NF-WB) stored for < 7days would: 4 Result in significant thrombocytopenia with Relative preservation of coagulation factor levels RESULTS: Hemostatic composition of the prime was the same following the use of either NF-WB or RWB 5

6 Dilutional Effect International Pediatric Perfusion Practice Surveys 2002 Survey: No mention of WB primes Both NF-WB and RWB prime for neonates/infants to reach a post-dilutional Hct of 30%: induces clinically significant dilutional thrombocytopenia with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, VIX, FX, plasminogen, and AT-III Platelet count decreased by 70-80% from baseline to end of CPB: ~ 60% of the decrease was dilutional Dilutional thrombocytopenia and hypofibrinogenemia also observed in other pediatric studies with large prime volumes of either PRBC or NF-WB were used to reach a target Hct Ped Anes 2009 (10-12) 2005 Survey: 24% of centers use WB for priming neonatal circuits 2011 Survey: No mention of WB priming 2017 Groom International Pediatric Survey World-Wide Pediatric Cardiac Center Respondents NON-NORTH AMERICA: 26,927 pediatric/infant/neonatal procedures at 67 non-north American centers over a 3-year period (8,975 procedures/year) 2017 Groom International Pediatric Survey North American Centers (89 US and 3 Canadian) NORTH AMERICA: 19,314 pediatric/infant/neonatal 92 centers (89 US / 3 Canada) in North America over a 3-year period (6,438 procedures/year) 6

7 Crystalloid Component of Prime 2017 Groom international Pediatric Survey Preliminary Results Blood Prime Components 2017 Groom international Pediatric Survey Preliminary Results Which of the following blood products do you use to prime the bypass circuit for the following age groups? (select all that apply): Neonatal circuit static prime volume (including min operating level and CPG if blood CPG is used): Average: 283 ml Minimum: 120 ml Maximum: 550 ml FWB Conclusions Techniques and equipment for neonatal CPB have significantly improved over the past 20 years, however optimal priming composition and fluid management for this group of patients remains unclear and varies tremendously from institution to institution 34 Use of FWB in prime has no advantage over RWB for congenital heart surgery and is associated with significantly increased ICU LOS & periop fluid overload 13 Only reproducible advantage to FWB prime is significantly decreased donor exposures: Alleviated by using single donor for PRBC & FFP Other authors have concluded there are no additional benefits for using FWB than decreasing donor exposures 25, 13 Unable to corroborate positive effects of FWB on postop blood loss or coagulation 20 Transfusion medicine standards do not support widespread use of FWB 6 Whole blood is not even available for use at some institutions Availability of Fresh Whole Blood WB transfusion is more common outside the US, especially in developing countries 90% of Vanderbilt University homologous blood products are provided by the local ARC: Nashville ARC will not routinely provide whole blood for transfusion Whole blood requires a physician order and is done as a special collection Utilizing WB would be more difficult from a blood banking perspective as it would limit the availability of specific component transfusions, which is perceived as an advantage over WB transfusions Age of homologous PRBC s: VCH definition of fresh </= 14 days old Pediatric cardiac surgery is usually ~ 2 days old (or generally between 5-14 days) After 14 days, it is used in the adult hospital Stephanie Sephel Manager, Transfusion Service Blood Bank Vanderbilt University Medical Center 7

8 OPTIMIZING NEONATAL PERFUSION Optimizing Neonatal Perfusion Hemostasis & Factor Replacement: Prime volume is a significant predictor of transfusion (P<.001). It is a risk factor we can easily influence 31 Largest contributor to neonatal post op bleeding is dilutional effect of bypass: 70-80% decrease from baseline resulting in clinically significant thrombocytopenia ATIII decrease by 50% Platelets: Thrombocytopenia prior to termination of CPB or following protamine administration correlates with excessive postop blood loss in children 10,16, 17 Volume-reduced platelets are effective in treating thrombocytopenia in a linear dose-related manner Fibrinogen: Hypofibrinogenemia is a key factor in dilutional coagulopathy following cardiac surgery 18,20 Neonatal and infant hemostasis may be further compromised by dysfunctional fibrinogen 21 Traditional thresholds for fibrinogen replacement following CPB are ~ mg/dl 22 Aggressive replacement of fibrinogen before concentrations fall below 100 mg/dl have been shown to reduce transfusion requirements despite the presence of thrombocytopenia Fresh blood products: Transfusing old blood is an independent predictor of multi-organ failure and in-hospital mortality 20 Increased storage of PRBC s has been associated with an increased risk of postop pneumonia and LOS in cardiac surgical population Gruenwald Pre-bypass Ultrafiltration (PreBUF): Reduces inflammatory, electrolyte, and metabolic disturbances and prevents large osmolal fluxes before initiating CPB 20 Balanced ultrafiltered prime may be particularly advantageous in single ventricle patients with: 11 higher markers of inflammation increased postop morbidity An easy & effective way to provide a balanced, physiological prime whether FWB or RWB is used 20 Multidisciplinary Communication: Coordinate post-bypass factor administration by anesthesia with our ability to decrease pt CBV and increase Hct during MUF Optimizing Neonatal Perfusion Utilizing priming protocols of combining various electrolyte solutions to match the patients physiology as closely as possible (TCH) Develop strategies to quantify/optimize COP in the prime and during bypass: Lower COP s are associated with longer ICU stay and higher mortality Need to continue looking for existing as well as emerging strategies and techniques to reduce CPB-related morbidities and optimize the neonates response to CPB 23 8

9 References References (continued) 1. Ann Thorac Surg. 1999;68: JaggersJJ, Neal MC, Smith PK, Ungerleider RM, Lawson JH. Infant cardiopulmonary bypass: a procoagulent state 2. Ann Thorac Surg. 1992;54: Kern FH, Morana NJ, Sears JJ, Hickey PR. Coagulation defects in neonates during cardiopulmonary bypass. 3. Ann Thorac Surg. 2002;73: Hovels-Gurich HH, Schumacher K, Vazquez-Jimenez JF, Qing M, Huffmeier U, Buding B, et al. Cytokine balance in infants undergoing cardiac operation 4. Guay J, Rivard G. Mediastinal bleeding after cardiopulmonary bypass in pediatric patients. Ann Thorac Surg. 1996;62: Blood. 1992;80: Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. 6. Anesth Analg. 1999;89: Williams GD, Bratton SL, Ramamoorthy C. Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open heart surgery. 7. Chan AK, Leaker M, Burrows FA, Williams WG, Gruenwald CE, Whyte L, et al 7. Thromb Haemost. 1997;77: Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. 8. Ann Thorac Surg. 1998;66: Williams GD, Bratton SL, Riley EC, Ramamoorthy C. Association between age and blood loss in children undergoing open heart operations. 9. NEJM 2004; 351: Fresh Whole Blood versus Reconstituted Blood for Pump Priming in Heart Surgery in Infants. 10. Ann Thorac Surg 1992; 54:541-6 Coagulation Defects in Neonates During CPB Kern F, Morana NJ et al. 11. JTCVS 2008; 136: Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: A randomized controlled trial. Greunwald et al. 12. Manno CS, Hedberg KW, Kim HC, Bunin GR, Nicolson S, Jobes D, et al. Comparison of the hemostatic effects of fresh whole blood, stored whole blood, and components after open heart surgery in children. Blood. 1991;77: Mou SS, Giroir BP, Molitor-Kirsch EA, Leonard SR, Nikaidoh H, Nizzi F, et al. Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants. N Engl J Med. 2004;351: Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, Starr NJ, et al. Morbidity andmortality risk associated with redblood cell and blood component transfusion 15. in isolated coronary artery bypass grafting. Crit Care Med. 2006;34: Vamvakas EC, Carven JH. Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: effect of the length of storage of transfused red cells. 17. Transfusion. 1999;39: Basran S, Frumento RJ, Cohen A, Lee S, Du Y, Nishanian E, et al. The association between duration of storage of transfused red blood cells and morbidity and 19. mortality after reoperative cardiac surgery. Anesth Analg. 2006;103: Valleley M, Buckley K, Hayes K, Fortuna R, Geiss D, Holt D. JECT. 2007;39: Are there benefits to a fresh whole blood vs. packed red blood cell cardiopulmonary bypass prime on outcomes in neonatal and pediatric cardiac surgery? 21. Nagashima M, Imai Y, Seo K, et al. Effect of hemofiltered whole blood pump priming on hemodynamics and respiratory function after the arterial switch operation in neonates. Ann Thorac Surg. 2000; 70: RidleyPD, Ratcliffe JM, Alberti KGMM, Elliot MJ. The metabolic consequence of a washed cardiopulmonary bypass pump-priming fluid in children undergoing cardiac operations. J Thorac Cardiovasc Surg. 1990;100: Shen I, Giacomuzzi C, Ungerleider RM. Current strategies for optimizing the use of cardiopulmonary bypass in neonates and infants. Ann Thorac Surg. 2003;75:S Ratcliffe JM, Elliot MJ, Wyse RK, Alberti KG. The metabolic load of stored blood. Implications for major transfusions in infants. Arch Dis Child. 1986;61: Madhok AB, Ojamaa K, Haridas V, Parnell VA, Pahwa S, Chowdhury D. Cytokine response in children undergoing surgery for congenital heart disease. Pediatr Cardiol. 2006;27: Friesen RH, Perryman KM, Weigers KR, Mitchell MB, Friesen RM. Pediatr Anesth. 2006;16: A trial of fresh autologous whole blood to treat dilutional coagulopathy following cardiopulmonary bypass in infants. 27. ADD 2011 ATS Update to Blood Conservation STS-SCA 28. Hornykewycz, S, Odegard K, Castro R, Zurakowski D, Pigula F, Dinardo J. Pediatric Anesthesia : Hemostatic consequences of a non-fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants. 29. Garg P, Bishnoi A, Patel S. Artificial Organs Vol. 41, No. 8, Hemodiafiltration A Technique for Physiological Correction of Priming Solution in Pediatric Cardiac Surgery: An In Vitro Study 30. Miao X, Liu J, Zhao M, Cui Y, Hu S. Perfusion 2015, Vol 30(2) Evidence-based use of FFP: the influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients. 31. Richmond M, Charette K, Chen J, Guaegebeur J, Bacha E. J Thor Cardiovasc Surg 2013, Vol 145, No 4 ( ). The effect of cardiopulmonary bypass prime volume on the need for blood transfusion after pediatric cardiac surgery. 32. Madhok AB, Ojamaa K, Haridas V, Parnell VA, Pahwa S, Chowdhury D. Cytokine resonse in children undergoing surgery for congenital heart disease. Pediatr Cardiol. 2006;27: Keidan I, Amir G, Mandel M, Mishali D. The metabolic effects of fresh versus old stored blood in the priming of cardiopulmonary bypass solution for pediatric patients. J Thorac Cardiovasc Surg. 2004;127: References (continued) 34. Darling E, Harris-Holloway S, Kern F, Ungerleider R, Jaggers J, Lawson S, Shearer I. Perfusion 2000; 15: Impact of modifying priming components and fluid administration using miniaturized circuitry in neonatal cardiopulmonary bypass. 35. Radcliffe JM, Wyse RK, Hunter S, Alberti KG, Elliott MJ. The role of the priming fluid in the metabolic response to cardiopulmonary bypass In children of less than 15 kg body weight undergoing open-heart surgery. Thorac Cardiovasc Surg 1988; 36: Haneta K, Sato S. Ishizawa E, Horiuchi T. The importance of colloid osmostic pressure during hearts surgery in infants. Tohoku J Exp Med 1985; 147: Gruenwald C, McCrindle B, Crawford-Lean L, Holtby H, Parshuram C, Massicotte P, Van Arsdell G. Jour Cardiothorac Vasc Surgery: Vol 136, No 6 pp Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: A randomized controlled trial. DISCUSSION: RFWB may be superior to traditional WB owing to: pre-storage leukocyte depletion (standard for blood component preparation in Canada, reducing leukocytes to 10-4 ; a value below which alloimmunization or suppression does not occur) Storage of platelets at room temperature (exhibit better hemostatic properties than when stored at cold temperatures, the routine in traditional WB storage) Difference in age of blood between the two study groups ( vs days) contributed to the improved clinical outcomes in the RFWB group: Significantly lower median inotropic score at 24 hours than component group Median age of PRBC s was 14 days: Increased storage of PRBC s has been associated with an increase in risk of postop pneumonia and an increased length of stay in cardiac surgical population Inflammatory markers showed a significantly greater increase in the component group (IL-8) 9

10 Previous studies using fresh WB to either prime the pump or meet postop transfusion needs have reported conflicting results J Thorac Cardiovasc 13,14 Objective: Compared effects of reconstituted fresh WB (RFWB) against standard blood component therapy (PRBC s) used in the prime, throughout CPB and for all transfusion requirements within the first 24 hours postoperatively in neonates undergoing CPB Methods: Patients < 1 month of age randomized to receive either RFWB (n=31) or PRBC therapy (n=33) Primary Outcome: chest tube drainage Secondary Outcome: transfusion needs, inotrope score, ventilation time, hospital length of stay BLOOD PRODUCT PREPARATION: Canadian Blood Services (CBS) require all donor blood be separated into components immediately after collection and leukocyte reduced by filtration before storage: Red blood cells Random donor platelets FFP All donor blood collected into bags containing citrate phosphate double dextrose (CPDD): PRBC components were stored in AS-3 preservative and stored at 33.8 o F to 42.8 o F All plasma was frozen within 8 hours of donation and stored at -0.4 o F Platelets were continually agitated during storage at 68 o F to 75.2 o F On the DOS morning, one of the RFWB units was prepared by reconstituting the components from the single donor previously described: All RFWB units were collected 2 days before the morning of operation PRBC and platelets were irradiated on the morning of the operation before either reconstitution or release as individual components Platelets were random single donor platelets collected 2-5 days (median 4 days) before DOS Reconstituted FWB vs. Reconstituted RESULTS: Component Group: RFWB: Significantly higher mean blood donor unit exposures (7+ 4 units) than the RFWB group (3 + 2 units) when CPB and postop blood transfusion requirements were included (P <.0001) Blood cells significantly older ( days) than in RFWB (2 days) (P <.0001) Bleeding described by surgeon more frequently as moderate or severe (82%) than in RFWB (55%) (P = 0.03) Significantly lower median inotropic score (3.3; 0-9.9) at 24 hours than component group (6.6; ) (P =.002) Median total ventilation hours or time to first extubation was significantly reduced (119; ) vs. 164; ) (P =.04) And hospitalization (bottom of page 1446; green HL, 2 nd column. Get range and P value ) No difference between groups: In median total volume transfused within study period 10

11 The use of RFWB affects 3 important parameters of blood transfusion: Age of infused cells Number of allogeneic donor exposures Platelet count during bypass Because the effect of RFWB is likely multifactorial, further analyses quantified the effect of each component: Chest tube loss at 24 hours, inotropic score at 24 hours, duration of ventilation, and hospital stay were all found to be significantly associated with age of blood product, exposure to allogeneic donors, and higher platelet count at end of bypass Component group: Lower platelet count at end of bypass and exposure to higher number of allogeneic donors were independent predictors of higher inotropic score at 24 hours Lower platelet count at end of bypass and older age of blood cells were independent predictors of longer duration of hospital stay DISCUSSION: RFWB may be superior to traditional WB owing to: pre-storage leukocyte depletion (standard for blood component preparation in Canada, reducing leukocytes to 10-4 ; a value below which alloimmunization or suppression does not occur) Storage of platelets at room temperature (exhibit better hemostatic properties than when stored at cold temperatures, the routine in traditional WB storage) Difference in age of blood between the two study groups ( vs days) contributed to the improved clinical outcomes in the RFWB group: Significantly lower median inotropic score at 24 hours than component group Median age of PRBC s was 14 days: Increased storage of PRBC s has been associated with an increase in risk of postop pneumonia and an increased length of stay in cardiac surgical population Inflammatory markers showed a significantly greater increase in the component group (IL-8) CONCLUSION: Advocates the use of single donor RFWB to prime the bypass circuit, throughout CPB, and for transfusion requirements during the first 24 hours postop Neonates who received RFWB had significantly improved clinical outcomes, including: Less postop chest tube volume loss during first 24 hours Significantly lower inotropic scores Decreased ventilation time Reduced hospital length of stay The last 3 factors were shown to be independently associated with a lower number of donor exposures Three factors in the RFWB group that independently contributed to these improved outcomes: Higher platelet count at 10 minutes and end of bypass This was associated with significantly reduced chest tube volume loss and is supported by other investigators 6 Reduced number of allogeneic donor exposures Younger age of blood products Cons Gruenwald study contradicts results from Mou and colleagues previous randomized controlled trial, 14 which found no differences in postop outcomes between component vs. FWB: Additionally, Mou study showed some secondary clinical measures and advantage for component therapy (PRBC) Use of FWB for priming only while using component therapy for further transfusion requirements may have obscured the effect of FWB The use of blood in both arms of the study that had not been leukodepleted could offset gains made by using FWB While Gruenwald showed clinical advantages of using RFWB in neonatal cardiac surgery, logistical issues may prevent replicating this strategy (single donor, fractionating/recombining components, maintaining platelets at room temperature while being agitated until recombination) Age of RBC s and platelets in component group was older than that used in other centers, but was within acceptable CBS standard operating procedures Assessment of blood loss in postop period only took into account drainage from chest tubes and did not account for blood collecting in pleural cavity or mediastinum for patients with open chests postop. Could underestimate total blood loss since difference was unevenly distributed between experimental groups 11