A comparison of health care and blood supply system structures.

There is great diversity in the practice of blood banking and transfusion medicine between countries. We sought to relate this to the variety of health care and blood supply systems in different countries. Questionnaires were completed by respondents from 15 countries selected from among those with higher Human Development Indices. These data were reviewed searching for correlations with blood banking and transfusion medicine practices. Wide varieties of health care and blood supply schemes were documented. There was no apparent relationship between their structure and organization nor their financing arrangements and their proclivity for the implementation of new methods or approaches such as pathogen inactivation and universal leucoreduction. The costs of the operation of the blood supply system as represented by their product fees and the rate of collection of red cells could also not be associated with the factors examined. The diversity of practice evident across developed countries is not explicable solely through their health care and blood supply system structures. Other factors are likely involved but are not easy to define or measure.

Reducing the variation in performance of antibody titrations.

BACKGROUND: Antibody titration is difficult to standardize. We investigated whether a detailed, uniform procedure for antibody titration would reduce variation in both tube-based and gel card titres in an international study. METHODS: Laboratories (n = 35) tested proficiency testing material provided by the College of American Pathologists each according to (i) their routine method; (ii) a detailed, uniform method; and (iii) the uniform method titrating the serum sample against a red cell of specified phenotype (D+ C- c+ E+ e- for anti-D; A(1) for anti-A) instead of the red cell of the same phenotype provided in the proficiency testing kit. Uniform method results were reported with 1+ and w+ end-points. Paired statistical analyses of variance were conducted using the F-test. RESULTS: The variance between laboratories was not significantly reduced with the uniform method using a 1+ end-point. However, a statistically significant reduction in the variance of anti-D and anti-A titres by the tube-based uniform technique after 37 degrees C incubation and conversion to the antiglobulin (AHG) phase was seen when 19 laboratories reanalysed their results using a w+ end-point. Too few laboratories reported results with a w+ end-point in gel card testing to allow analysis. Titration against red cells of the specified phenotype provided by the participating laboratory did not appear to introduce additional variance. Overall, results reported based on the gel card technique at the AHG phase (1+ end-point) showed reduced variance compared to tube-based techniques. CONCLUSIONS: A detailed, uniform method for antibody titration at 37 degrees C and read at the AHG phase in a tube-based method with a w+ end-point reduced interlaboratory variability.

Preclinical trial of a radiant heat device for whole-body hyperthermia using a porcine model.

After review of the published clinical experience with systemic hypothermia, we concluded that a simple system which controls radiant heat balance to supplement metabolic heat might provide several advantages, including: (a) decreased morbidity; (b) elimination of the requirement for general anesthesia; (c) improved patient comfort; (d) favorable cost-benefit considerations. We have tested a prototype radiant heat device for whole-body hyperthermia (WBH) in patients with disseminated cancer. From preclinical evaluation of this device, the lightly anesthetized pig was found to be an ideal model for WBH. This species has physiological characteristics closely resembling those of humans. The pig's core, pulmonary artery, liver, rectal, and esophageal temperatures were raised to 41.8 degrees in 80 to 90 min. The air temperatures near the chamber wall never exceeded 65 degrees while the air temperature adjacent to the animal was 46 degrees. Skin temperatures were approximately 42.5 degrees at a core temperature of 41.8 degrees. Once the core temperature is raised to 41.8 degrees, this temperature is maintainable for approximately 3.5 hr without additional external heating if evaporative losses are controlled. Prolonged WBH was accomplished with light sedation and without the requirement for endotracheal intubation. No significant acute toxicity was encountered in a series of 6 pigs undergoing 9 separate exposures to WBH. From these results, we conclude that our radiant heat apparatus is feasible for clinical trials. Additionally, the use of the pig as an appropriate animal model for further physiological and pharmacological WBH studies is strongly recommended.

Cost-effectiveness of preoperative autologous blood donation for orthopedic and cardiac surgeries.

Decision analysis techniques can be used to determine objectively the health improvement benefit obtained from a medical intervention relative to the resources required for the intervention. Such calculations can help direct societal healthcare policies but may not be directly applicable to an individual patient. However, these analyses can still be used to indicate those situations in which an intervention is most beneficial and those in which its use may not be appropriate. Preoperative autologous blood donation (PABD), for example, may not be cost-effective if blood units are collected when they are not likely to be used or if such units are transfused solely because they are available. Furthermore, the risks associated with PABD may exceed those of the allogeneic transfusion that the patient seeks to avoid, particularly in patients with significant cardiac disease. In such settings, careful, objective analyses may help direct not only healthcare policy but also hemotherapy practice for individual patients.

Acoustic microscopy of red blood cells.

We used a scanning acoustic microscope to image normal and outdated red blood cells, cells with different hemoglobin content, red cell ghosts, and cells treated with various drugs that induce echinocyte-stomatocyte transformation. Images were obtained at different planes of focus within the cells, corresponding to maxima and minima of signal intensity. Digitization and gray scale amplitude mapping were used to create axonometric plots that display signal amplitude variations within the cells. The images of red cells contain features produced by differences in topology, density, elasticity, and absorption. Both hemoglobin content and the cell cytoskeleton contribute to image features, and various deformations, characterized by the formation of blebs and vacuoles, are displayed in cells undergoing echinocyte-stomatocyte transformation. These preliminary findings, although mainly descriptive, indicate that acoustic microscopy may be a useful new method for evaluating red cell deformation and associated changes in mechanical properties.

Practical methods to improve transfusion safety by using novel blood unit and patient identification systems.

Human error is a leading cause of transfusion-associated death. Many of these events are associated with a failure to comply with established unit-recipient identification protocols. Although several dedicated systems designed to minimize this problem are currently available, none of them have been sufficiently challenged by the various conditions that exist in diverse clinical settings. However, data available for computer-based recognition procedures and for a disposable blood bag combination lock, which precludes access to the blood before it is properly identified, are encouraging.

Cost-effectiveness of preoperative autologous donation in coronary artery bypass grafting.

Concern about the safety of the allogeneic blood supply has made preoperative autologous blood donation (PAD) routine before major noncardiac operations. However, the costs and benefits of PAD in elective coronary artery bypass grafting (CABG) are not well established. We used decision analysis to (1) calculate the cost-effectiveness of PAD in CABG, expressed as cost per year of life saved, and (2) compare the health benefits of reducing allogeneic transfusions with the potential risks of autologous blood donation by patients with coronary artery disease. A prospective study of 18 institutions provided data on transfusion practice and blood product costs in CABG. On average, PAD in CABG costs $508,000 to $909,000 per quality-adjusted year of life saved, depending on the number of units donated. Preoperative autologous blood donation is more cost-effective (as low as $518,000 per year of life saved) when targeted to younger patients undergoing CABG at centers with high transfusion rates. The cost-effectiveness of PAD is strongly dependent on estimates of posttransfusion hepatitis incidence, but less so on plausible estimates of the current risk of human immunodeficiency virus transmission. Although the actual risk of PAD is uncertain, even a small fatality risk (> 1 per 101,000 donations) associated with blood donation by patients awaiting CABG negates all life expectancy benefits of PAD. At current costs, PAD by patients awaiting CABG is not cost-effective, producing small health benefits at high societal cost. For the individual patient, the risk of donating blood before CABG may well outweigh the benefits associated with fewer allogeneic transfusions.

Platelet transfusion therapy.

Although platelet transfusion is a vital part of modern hemotherapy, many related issues are unresolved. The most appropriate trigger point of transfusion and the clinical utility of prophylactic transfusion are still debated, but the importance of patient-specific transfusion decisions is clear. Leukocyte reduction and single donor platelets may have important roles in avoiding complications, but more data are needed. Establishment of a standardized protocol for managing patients receiving ongoing platelet transfusions may facilitate application of special techniques and the use of specially chosen units that provide better platelet support for thrombocytopenic patients.

Inactivation of microbial contaminants of blood components.

Despite the low risk of transfusion-transmitted infection currently present in the blood supply, processes to inactivate contaminating viruses and bacteria may improve the safety of transfusion even further. A variety of techniques, using both physical and chemical processes, are being explored. Particularly promising is adaptation of the solvent/detergent technique (already in use for plasma derivatives) to plasma for transfusion. Inactivation of viruses in cellular components may require a combination of techniques, possibly including leukocyte depletion filtration, photoactive compounds, and subsequent washing. Concerns about potential toxicity of the agents employed and retention of component efficacy after treatment and storage remain unresolved, however.

Blood transfusion options: improving outcomes and reducing costs.

OBJECTIVE: To identify means of improving provision of transfusion services to patients while reducing hospital costs, focusing on the practice of transfusion medicine and laboratory operations in a hospital. DATA SOURCES: English language literature, 1990 to present. STUDY SELECTION: Case reports, controlled trials, and reviews. CONCLUSIONS: Owing to fixed reimbursements, hospitals are seeking ways to reduce operational costs while maintaining patient care standards. In transfusion medicine, this can be accomplished through recognition of direct and indirect costs of transfusion, careful examination of transfusion criteria, and selection of laboratory procedures that truly add to patient safety.

The role of transfusion medicine physicians. A vanishing breed?

Physicians with interest or expertise in transfusion medicine must apply their clinical consultation and laboratory management skills to be accorded support for their activities. To establish credibility, efforts must initially be directed where patient benefit and financial gain can be documented. Focusing efforts on practice improvements and sharing the results of those efforts with physician colleagues and administrators can help ensure continued support. Transfusion medicine continues to play an important role in health care, particularly in an era of managed care and reduced resources. Investment in the activities of this discipline will pay off for patients, clinicians, and hospitals.

Optimizing the cost-effectiveness of quality assurance in transfusion medicine.

Although quality assurance efforts have been integrated into many aspects of American health care, their value has been questioned. They can consume large amounts of resources (monetary and/or temporal), calling into question their cost-effectiveness. To improve the yield of quality assurance efforts and limit their consumption of administrative resources, they need to be focused on those aspects of the operation where improvement is needed or where errors are particularly problematic and costly. Just as a quality assurance program needs to define the outcome required of the process being monitored, the outcome of the quality assurance process needs to be defined at the outset; the simplest possible system should then be designed to capture the necessary data to direct improvement. Although quality assurance efforts have been documented to yield substantial savings, their real payback is provided through better control of an operation and more complete knowledge of the status of that operation.

Minimizing donor exposure in hemotherapy.

As with any medical therapy, transfusion has risks and complications that are inherent in its application. There are also many options in standard approaches and alternatives to allogeneic transfusion to be considered that allow hemotherapy to be tailored to the patient's needs, maximizing benefit while reducing risk. Transfusion of standard, allogeneic components selected at random and derived from an altruistic donation by a community volunteer donor continue to comprise the majority of transfusions. However, many steps can be taken to minimize allogeneic exposure and its consequences. Transfusing only when the benefits are clinically important and justify the risks is probably most important. Options abound for pharmacologic intervention, altering collection systems and using the donor as his or her own source of blood to further reduce allogeneic exposure.

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.

Evaluation of a rapid technique for antibody elution.

This study evaluated a new rapid acid elution technique using citric acid. This technique was compared to the commonly used digitonin acid procedure. Twenty patient or donor antibodies with specificities in the Rhesus, Kell, Kidd, or Duffy systems were used to coat red cells. Eluates produced from these cells by the citric acid procedure were equivalent or greater in volume and potency to those produced by a digitonin acid method. The citric acid procedure required five to nine minutes to complete, while the digitonin acid procedure required 28 to 44 minutes. The citric acid technique is a rapid means of producing a potent eluate.

False reactivity in GTI Pak Plus ELISA kits due to the presence of anti-mouse antibody in patients' samples.

The development of commercially available ELISA kits (GTI, Inc., Waukesha, WI) that use antigens adhered to microtiter plate wells by the use of mouse monoclonal antibodies made it possible for hospital transfusion service laboratories to test for platelet- and/or HLA-specific antibodies without reliance on reference laboratories. However, human anti-mouse antibodies (HAMAs) may cause false reactions in ELISAs. We designed a study to determine the impact of HAMAs on these ELISAs. Samples from 210 patients were evaluated from January 1995 to April 2002; 79 (38%) were found to be positive for HLA- and/or platelet-specific antibodies. Thirty (38%) of these positive samples,as well as ten negative samples that served as controls, underwent HAMA neutralization/inhibition procedures before being retested by ELISA. One (10%) of the control samples was reactive after treatment. When the samples that were positive in routine testing were treated to neutralize/inhibit HAMAs, reactivity was unchanged in 20 (67%); reactivity was eliminated in eight (27%) of the samples tested. All of the specimens that showed a reduction or elimination of their reactivity after neutralization/inhibition had an initial optical density (OD) ratio < 3.0 whereas those that remained unchanged in reactivity had an OD ratio > 7.0 (p < 0.05). Reactivity present only in the treated samples was observed in three (10%) of the positive samples tested;one was additionally reactive with HLA antigen only and two with glycoprotein Ia/IIa. The presence of HAMAs should be considered when antibodies against more than one platelet-specific glycoprotein are detected and if the optical density ratio is < 3.0.

Frequency of thrombocytopenia associated with gentamicin therapy.

Many drugs, including antibiotics such as gentamicin, have been associated with the development of a drug-induced thrombocytopenia. Serologic methods for detection of drug-dependent platelet antibodies (DDPAs) are not routinely performed, and the incidence of such antibody-mediated thrombocytopenia is not known. As we routinely perform solid-phase red cell adherence assays for the detection of DDPAs, a study was designed to determine the incidence of gentamicin- associated platelet antibodies (GAPAs) in our institution. Adult patients who received gentamicin from 1/1/98 to 7/31/98 were evaluated for inclusion in the study. Testing for the presence of GAPAs was performed if the patient had a decrease in platelet count while receiving gentamicin or if the platelet count increased or decreased within 3 days of the last gentamicin therapy. Patients receiving gentamicin without development of thrombocytopenia were tested as controls. During the study period, 926 patients received gentamicin, with 324 (35%) being evaluated for the presence of GAPAs; GAPAs were identified in 25 of 659 patients (4%) eligible for the study. All control samples were found to lack GAPAs. If only patients exhibiting changes in platelet counts are considered, the incidence increases to 7.7 percent, with females apparently being almost twice as likely to develop GAPAs than are males. Gentamicin-associated thrombocytopenia is not an infrequent occurrence in hospitalized patients.

Development of anti-Bw6 reactivity in patients receiving r-GCSF: a preliminary report.

Recombinant granulocyte colony-stimulating factor (r-GCSF) is used in autologous bone marrow/peripheral blood progenitor cell transplantation (ABMT/PBPC) to shorten the period of neutropenia. As these patients require platelet transfusions, their sera may be monitored for the presence of platelet/human leukocyte antigen (HLA) antibodies. Sera of some patients on r-GCSF (16 microg/kg/day) became difficult to evaluate in vitro for the presence of HLA and platelet antibodies because of apparently anomalous reactions in solid phase red cell adherence (SPRCA) assays. SPRCA tests were positive only when platelets were adhered to the polystyrene plates in the presence of glucose; when other simple sugars were used, the patients' sera failed to react. HLA Bw6-positive platelets were more likely than HLA Bw6-negative platelets to be reactive (p <.001). The transfusion of HLA Bw6-positive platelets to patients displaying this in vitro reactivity (positive patients) resulted in a 50 percent lower corrected count increment (CCI) than those given to patients without it (negative patients; p = <.001). When all transfusions were considered, the CCI for those of the positive patients was decreased 73 percent when compared to the control patients (p =.0005). The presence of the antibody also was associated with a twofold increase in the number of platelet transfusions given (p =.0005). ABMT/PBPC patients receiving r-GCSF may develop unexpected reactions on SPRCA antibody screens and poor responses to transfusion of Bw-6-positive platelets.