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Biomedical subjects

J P AuBuchon

Publications and source records attributed to J P AuBuchon.

At least 19 recordsLinked to original sources
PubMed2007

Extended storage of red blood cells under anaerobic conditions.

BACKGROUND: Red blood cells (RBC) are subject to oxidative stress by reactive oxygen species during refrigerated storage. Near-complete removal of oxygen from red cells during storage should eliminate this contributor to the red cell 'storage lesion'. The in vitro effects of storing red cells under oxygen-depleted conditions for extended periods were investigated, and these were correlated with the observed recoveries after reinfusion. STUDY DESIGN AND METHODS: Units of red cells, obtained after 'soft spin', were placed in a double volume of AS-3 additive solution and subdivided. Oxygen in the test units was depleted by repeated exposure to Ar gas (to O(2) saturation < 4%), and units were stored in anaerobic canisters for up to 15 weeks. Samples were taken weekly to monitor adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), cell-free haemoglobin, and vesicle production. In a parallel experiment, six units of red cells was depleted of oxygen in a similar manner, stored for 8, 9 and 10 weeks, and reinfused autologously to determine the 24 h post-transfusion recovery via (51)Cr/(99m)Tc radiolabelling. A similar study was also carried out using EAS61 additive solution, which by itself, had shown the ability to support 9-week storage, comparing biochemical profiles and in vivo recovery after aerobic vs. anaerobic storage. RESULTS: Oxygen-depleted AS-3 units had significantly elevated ATP levels compared to controls. They also had significantly lower cell free haemoglobin and vesicle production when RBCs were stored for more than 9 weeks. An average of over 75% post-transfusion survival was observed after 9 weeks of anaerobic storage with less than 0.43% haemolysis. However, no further extension of storage was achieved with EAS61 additive. CONCLUSION: Anaerobic conditions permit acceptable 9-week storage of RBCs using double-volume AS-3 additive solution. It did not synergize with the alkaline, 9-week additive, EAS61, to further lengthen the acceptable storage time. These studies indicate that anaerobic storage may allow reduction in the effect of the storage lesion, but suggest that other factors contribute to limitations of RBC storage as well.

Anaerobiosis↗
PubMed2005

Interlaboratory comparison of red-cell ATP, 2,3-diphosphoglycerate and haemolysis measurements.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) storage systems are licensed based on their ability to prevent haemolysis and maintain RBC 24-h in vivo recovery. Preclinical testing includes measurement of RBC ATP as a surrogate for recovery, 2,3-diphosphoglycerate (DPG) as a surrogate for oxygen affinity, and free haemoglobin, which is indicative of red cell lysis. The reproducibility of RBC ATP, DPG and haemolysis measurements between centres was investigated. MATERIALS AND METHODS: Five, 4-day-old leucoreduced AS-1 RBC units were pooled, aliquotted and shipped on ice to 14 laboratories in the USA and European Union (EU). Each laboratory was to sample the bag twice on day 7 and measure RBC ATP, DPG, haemoglobin and haemolysis levels in triplicate on each sample. The variability of results was assessed by using coefficients of variation (CV) and analysis of variance. RESULTS: Measurements were highly reproducible at the individual sites. Between sites, the CV was 16% for ATP, 35% for DPG, 2% for total haemoglobin and 54% for haemolysis. For ATP and total haemoglobin, 94 and 80% of the variance in measurements was contributed by differences between sites, and more than 80% of the variance for DPG and haemolysis measurements came from markedly discordant results from three sites and one site, respectively. In descending order, mathematical errors, unvalidated analytical methods, a lack of shared standards and fluid handling errors contributed to the variability in measurements from different sites. CONCLUSIONS: While the methods used by laboratories engaged in RBC storage system clinical trials demonstrated good precision, differences in results between laboratories may hinder comparative analysis. Efforts to improve performance should focus on developing robust methods, especially for measuring RBC ATP.

2,3-Diphosphoglycerate↗
PubMed2004

Cost-effectiveness of nucleic acid test screening of volunteer blood donations for hepatitis B, hepatitis C and human immunodeficiency virus in the United States.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the cost-effectiveness of adding nucleic acid testing (NAT) to serological (antibody and antigen) screening protocols for donated blood in the United States (US) with the purpose of reducing the risks of transfusion-transmission of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). MATERIALS AND METHODS: The costs, health consequences and cost-effectiveness of adding either minipool or individual-donor NAT to serological screening (SS) testing were estimated using a decision-analysis model. RESULTS: With the given modelling assumptions, adding minipool NAT would avoid an estimated 37, 128 and eight cases of HBV, HCV and HIV, respectively, and save approximately 53 additional years of life and 102 additional quality adjusted life years (QALYs) compared with SS, at a net cost of $154 million. SS + minipool NAT - p24 compared with SS alone resulted in an incremental cost-effectiveness ratio of $1.5 million per QALY gained (range in sensitivity analysis $1.0-2.1 million per QALY gained) in this US analysis. CONCLUSIONS: The cost effectiveness of adding NAT screening is outside the typical range for most healthcare interventions, but not for established blood safety measures.

Blood Donors↗
PubMed2004

Platelet storage solution affects on the accuracy of laboratory tests for platelet function: a multi-laboratory study.

BACKGROUND AND OBJECTIVES: Extent of shape change (ESC) and hypotonic shock response (HSR) have been widely used to characterize the in vitro function of platelets and have been shown to correlate with in vivo viability. These assays have been routinely performed using platelet-poor plasma (PPP) as the test sample diluent. Because of the increasing popularity of storing platelets in synthetic media, it is important to understand the effects of using these synthetic media as test diluents for ESC and HSR measurements. The objective of this study was to determine the effect of using platelet storage solutions vs. plasma for the in vitro testing of ESC and HSR. MATERIALS AND METHODS: Six laboratories participated in this study. Platelets were prepared by apheresis, the platelet-rich plasma (PRP) method, or derived from buffy-coats. Each platelet preparation was divided, half being stored in plasma and the other half in storage solution. ESC and HSR testing were performed in duplicate on days 1 and 5, using each of three diluents: autologous plasma; fresh-frozen plasma; or storage solution. RESULTS: For both ESC and HSR, dilutions made in each of the three diluents yielded significantly different results. Dilutions made in storage solutions were more than 30% lower for ESC and HSR than those made in autologous plasma (P < 0.0001). Dilutions made in thawed fresh-frozen plasma were more than 16% lower for ESC and HSR than those made in liquid autologous plasma (P < 0.0005). CONCLUSIONS: ESC and HSR test results are significantly affected by the test diluent. Platelets should be diluted in plasma (preferably autologous) for the in vitro testing of ESC and HSR, regardless of the media in which they are stored.

Blood Platelets↗
PubMed2003

Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium.

BACKGROUND AND OBJECTIVES: In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS-III) was found to have a significant influence on platelet metabolism (using apheresis-derived, as well as buffy-coat-derived platelets) when compared with standard PAS-III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS-III containing 20% plasma was comparable to storage in standard PAS-III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted. MATERIALS AND METHODS: Platelets from 30 pools of approximately 20 buffy coat (BC) units each and 24 pooled apheresis platelet units were aliquoted for storage in plasma (reference) or synthetic medium using either a specific additive solution (PAS-III) containing 30% plasma or a modification of PAS-III containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM) and either 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days during which in vitro testing was carried out for biochemical, haematological and functional parameters. RESULTS: Storage of platelets in PAS-IIIM resulted in a reduction in the rate of glycolysis and better retention of pH and hypotonic shock response reactivity. Storage in PAS-IIIM containing 20% plasma appeared to result in the retention of in vitro properties, similar to those observed during storage in standard PAS-III containing 30% plasma. CONCLUSIONS: The results of this study confirm the preliminary results. Similar results were seen with platelets prepared by BC and apheresis methods, despite differences in equipment, the preparation technique and in the final platelet contents achieved in the platelet units. Storage of platelets in PAS-IIIM should be considered to improve platelet function and allow plasma reduction to 20%.

Blood Component Removal↗
PubMed2003

The cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations.

BACKGROUND: The risk of viral infection associated with blood transfusion is lower than ever before because of aggressive screening and testing practices. NAT technology has lowered that risk even further but at an additional cost to the health-care system. STUDY DESIGN AND METHODS: Marginal cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations was calculated with a previously published Markov decision model. This model was updated with disease incidence data from all 2001 American Red Cross whole-blood donations as well as window-period data from the Retrovirus Epidemiology Donor Study (REDS). RESULTS: Whole-blood donation NAT for HIV and HCV is expected to cost between 155 US dollars million (minipool NAT) and 428 million US dollars(single-donation NAT) per year in the US and avert 4 to 7 HIV infections and 56 to 59 HCV infections. Adding HBV NAT would be expected to avert 9 to 37 HBV infections at an additional cost of between 39 million US dollars and 130 million US dollars per year. Overall, NAT would cost between 4.7 million US dollars and 11.2 million US dollars per quality-adjusted life-year saved. Discontinuing HIV p24 antigen and HBc testing would offset this somewhat. CONCLUSIONS: The cost-effectiveness of whole-blood NAT is poor. The testing cost would need to decrease significantly to bring the cost-effectiveness in line with most other accepted medical practices.

Blood Donors↗
PubMed2002

Making risk statements stick.

Estimates of risk associated with blood transfusion are reported from a variety of sources using different numerical constructs. These data must be judged for validity and generalizability to facilitate decisions for interventions and to estimate potential benefits of interventions. Risk estimates reported in consistent terms, such as occurrences per million units transfused, will assist in comparisons of risks and the expected effect observed at the practitioner level. Use of the estimated number needed to treat puts the effect of an intervention in perspective for the individual practitioner and for national health authorities. We re-evaluated data reported from several recent studies of transfusion risk to highlight this approach. In the USA, the number needed to treat estimated to prevent one HIV transmission is 4.3 million (mini-pool NAT); to prevent one death from bacterial sepsis is 21 thousand (conversion to single donor platelets), and 16 thousand (bacterial screening of platelet concentrates). As interventions are continuing to drive infectious disease transmission rates lower and lower, expressing residual risk as the number needed to treat demonstrates that further improvements in safety are unlikely to be recognized at the local level even though the overall impact at the national level is significant.

Hemolysis↗
PubMed2002

Storage of platelets in additive solutions: a pilot in vitro study of the effects of potassium and magnesium.

BACKGROUND AND OBJECTIVES: Platelet additive solutions (PAS) have been shown to be suitable for extended platelet storage but have required the carryover of substantial (30%) amounts of plasma for success. Improving platelet quality by optimizing the composition of PAS may allow a reduction to be made in the amount of plasma carried over. Reducing the proportion of plasma carried over would facilitate some methods of viral inactivation and make available greater amounts of plasma for other needs. MATERIALS AND METHODS: Platelets from six pools of 25 buffy coat platelet units and five apheresis platelet units were aliquoted for storage in plasma, or converted to PAS units in either a specific additive solution (PAS-III), with 30% or 20% plasma, or a modification of PAS-III containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM), with 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days with in vitro testing for biochemical, haematological and functional parameters. RESULTS: Storage of platelets in PAS-IIIM resulted in a reduced rate of glycolysis and better retention of pH, morphology score and ATP levels. Platelets initially showed less evidence of activation when stored in PAS-IIIM, with reduced P-selectin expression. Storage in PAS-IIIM with 20% (rather than the standard 30%) plasma appeared to result in the retention of in vitro properties, similarly to storage in standard PAS-III with 30% plasma. CONCLUSIONS: Storing platelets in an additive solution containing magnesium and potassium improves the functionality of the platelets, as measured by in vitro testing, and may allow a reduction of the amount of plasma required to be carried over to the final unit.

Adenosine Triphosphate↗
PubMed2000

The cost-effectiveness of postoperative recovery of RBCs in preventing transfusion-associated virus transmission after joint arthroplasty.

BACKGROUND: The return of joint drainage after hip and knee arthroplasty is a widely used but expensive blood-conservation technique. STUDY DESIGN AND METHODS: A Markov decision analysis model was used to evaluate the cost-effectiveness of postoperative RBC recovery in preventing viral complications of allogeneic transfusion. RESULTS: In the baseline analysis, using an RBC-recovery device saves 5 quality-adjusted minutes of longevity at an average incremental cost of $53. This corresponds to $5.7 million per quality-adjusted life year. This figure was most sensitive to the direct cost differences of allogeneic versus recovered RBCs and to the volume of RBCs recovered per device. Such devices would save health care resources if they cost less than $73 or if they were applied only in cases where joint drainage was between 600 and 1100 mL. CONCLUSION: For most clinical situations, postarthroplasty RBC recovery does not appear to be as cost-effective as most other medical interventions. Clinical attention should be directed toward developing protocols for the preferential use of postoperative RBC-recovery devices in situations where they provide the greatest benefit.

Arthroplasty, Replacement, Hip↗
PubMed2000

Transfusion to blood group A and O patients of group B RBCs that have been enzymatically converted to group O.

BACKGROUND: The transfusion of ABO-incompatible RBCs is the leading cause of fatal transfusion reactions. Group O RBCs, lacking terminal immunodominant A and B sugars to which humans are immunized, are safe for transfusion to persons of any ABO blood group. With the use of a recombinant alpha-galactosidase to remove terminal galactose from group B RBCs, the safety and efficacy of enzyme-converted group-B-to-group-O (ECO) RBC components were studied in transfusion-dependent patients. STUDY DESIGN AND METHODS: Twenty-four patients (blood groups A and O) were randomly assigned to receive transfusion(s) of either ECO or control group O RBCs. If a second transfusion was given, the other blood component was administered. RESULTS: Twenty-one patients were given ECO RBCs; 18 also underwent control transfusions. One patient received only a small aliquot for RBC survival studies, instead of a full-unit transfusion, because his serum was incompatible with ECO RBCs. No adverse events occurred. Both ECO and control transfusions resulted in appropriate Hb increments and comparable (51)Cr-labeled RBC survival studies. One patient developed a transient, weak-positive DAT, without hemolysis. Two weeks after transfusion, 5 of 19 evaluable ECO RBC recipients had increases in anti-B titers. CONCLUSION: ECO RBCs were comparable to group O cells for safety and efficacy in this study. The clinical significance of the increase in anti-B and of occasional serologic incompatibilities with ECO RBCs is unclear. If strategies can be developed to remove A epitopes, enzymatic conversion could be used to create a universal (group O) donor blood supply.

ABO Blood-Group System↗
PubMed2000

Cost-effectiveness of new blood safety technologies.

Decision analysis techniques can be used to project the health benefit obtained by commitment of a given amount of resources. Such analyses can help physicians choose approaches offering the greatest benefit with the least risk, and can help health planners direct resources to where they will provide the greatest benefit. As the risks of allogeneic transfusion continue to decline, the yield of additional safety improvements necessarily diminishes, making their cost-effectiveness astronomically poor. While society may choose to direct our efforts in this direction, the value obtained by focussing attention on these areas of minimal yield should be clarified.

Biological Products↗