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Biomedical subjects

Jeffrey L Winters

Publications and source records attributed to Jeffrey L Winters.

14 recordsLinked to original sources

Complications of donor apheresis.

A decreasing blood donor pool in the presence of increasing blood transfusion demands has resulted in the need to maximally utilize each blood donor. This has led to a trend in the increasing use of automated blood collections. While apheresis donation shares many reactions and injuries with whole blood donation, because of the differences, unique complications also exist. Overall, evidence in the literature suggests that the frequency of reactions to apheresis donation is less than that seen in whole blood donation, though the risk of reactions requiring hospitalization is substantially greater. The most common apheresis-specific reaction is hypocalcemia due to citrate anticoagulation, which, while usually mild, has the potential for severely injuring the donor. Other reactions to apheresis donation are uncommon (e.g., hypotension) or rare (e.g., air embolism). More worrisome, and in need of additional study, are the long-term effects of apheresis donation. Recent evidence suggests that repeated apheresis platelet donations may adversely effect thrombopoiesis as well as bone mineralization. Granulocyte donation has also been implicated in unexpected long-term consequences.

Blood Component Removal↗

Evidence-based red cell transfusion in the critically ill: quality improvement using computerized physician order entry.

OBJECTIVE: The implementation of evidence-based practice poses a significant challenge in the intensive care unit. In this quality improvement intervention we assessed the effect of an institutional protocol and computerized decision support for red cell transfusion in the critically ill. DESIGN: We compared processes of care and outcomes during the two 3-month periods before and after the introduction of a multidisciplinary quality improvement intervention. SETTING: Multidisciplinary intensive care units--medical, surgical, and mixed--in a tertiary academic center. PATIENTS: Consecutive critically ill patients with anemia (hemoglobin of <10 g/dL). INTERVENTION: Using the computerized provider order entry, we developed an evidence-based decision algorithm for red cell transfusion in adult intensive care units. MEASUREMENTS AND MAIN RESULTS: We collected information on demographics, diagnosis, severity of illness, transfusion complications, and laboratory values. The main outcome measures were number of transfusions, proportion of patients who were transfused outside evidence-based indications, transfusion complications, and adjusted hospital mortality. The mean number of red cell transfusions per intensive care unit admission decreased from 1.08 +/- 2.3 units before to 0.86 +/- 2.3 units after the protocol (p<.001). We observed a marked decrease in the percentage of patients receiving inappropriate transfusions (17.7% vs. 4.5%, p< .001). The rate of transfusion complications was also lower in the period after the protocol (6.1% vs. 2.7%, p = .015). In the multivariate analysis, protocol introduction was associated with decreased likelihood of red cell transfusion (odds ratio, 0.43; 95% confidence interval, 0.30 to 0.62). Adjusted hospital mortality did not differ before and after protocol implementation (odds ratio, 1.12; 95% confidence interval, 0.69 to 1.8). CONCLUSIONS: The implementation of an institutional protocol and decision support through a computerized provider order entry effectively decreased inappropriate red cell transfusions.

Algorithms↗

Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study.

BACKGROUND: Using the recent Consensus Panel recommendations, we sought to describe the incidence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in critically ill patients. STUDY DESIGN AND METHODS: Consecutive patients at four intensive care units (ICUs) who did not require respiratory support at the time of transfusion were identified with custom electronic surveillance system that prospectively tracks the time of transfusion and onset of respiratory support. Respiratory failure was defined as the onset of noninvasive or invasive ventilator support within 6 hours of transfusion. Experts blinded to specific transfusion factors categorized the cases of pulmonary edema as permeability edema (suspected or possible TRALI) or hydrostatic edema (TACO) according to predefined algorithm. In a nested case-control design, transfusion variables and lung injury risk factors were compared between the TRALI cases and controls matched by age, sex, and admission diagnosis. RESULTS: There were 8902 units transfused in 1351 patients of whom 94 required new respiratory support within 6 hours of transfusion. Among 49 patients with confirmed acute pulmonary edema, experts identified 7 cases with suspected TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and fluid balance in a stepwise conditional logistic regression analysis, patients who developed acute lung injury (suspected or possible TRALI) received larger amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each liter infused; p = 0.023). CONCLUSION: In the ICU, pulmonary edema frequently occurs after blood transfusion. The association between infusion of plasma and the development of suspected or possible TRALI may have important implications with regards to etiology and prevention of this syndrome.

Aged↗

A novel source of viable peripheral blood mononuclear cells from leukoreduction system chambers.

BACKGROUND: Buffy coats are becoming less available as a source of research-grade peripheral blood mononuclear cells (PBMNCs). Therefore, alternative sources of these cells were investigated. STUDY DESIGN AND METHODS: PBMNCs isolated from the cells retained in leukoreduction system chambers (LRSCs) and those eluted from white blood cell filters were compared. From LRSCs (1.88 +/- 0.40) x 10(9) PBMNCs (n = 13) versus (0.43 +/- 0.15) x 10(9) PBMNCs were isolated from leukofilter eluates (LFEs, n = 8; p < 0.0001). RESULTS: Cells from LRSCs and LFEs produced similar numbers of burst-forming unit-erythroid, colony-forming unit (CFU)-granulocyte-macrophage, and CFU-granulocyte-erythrocyte-monocyte-macrophage-megakaryocyte colonies. The percentages of cells positive for CD3, CD4, CD8, CD14, CD19, and CD56 in the PBMNCs isolated from LRSCs and LFEs were indistinguishable. Cells isolated from LRSCs expressed higher levels of CD69 and CD25 in reaction to staphylococcal enterotoxin B than the cells isolated from LFEs. The source of cells affected neither the yield and purity of immunomagnetically isolated CD3+ cells, CD14+ cells, and CD56+ cells nor the function of T cells, natural killer cells, and in vitro matured dendritic cells (DCs). DC yield from LRSC-derived CD14+ cells, however, was higher. CONCLUSION: LRSCs are a novel source of fully functional PBMNCs that can replace the more traditional sources of research-grade cellular products.

Dendritic Cells↗

A Comparison of splenectomy versus intensive posttransplant antidonor blood group antibody monitoring without splenectomy in ABO-incompatible kidney transplantation.

BACKGROUND: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. METHODS: We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). RESULTS: Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. CONCLUSIONS: Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.

ABO Blood-Group System↗

Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration (AMD).

The primary goals are to provide a comprehensive explanation of the potential role of therapeutic apheresis in the treatment of Age-Related Macular Degeneration (AMD). Initial clinical results with this technique and a summary of current literature that addresses the mechanism of action for the Rheopheresis approach are presented. Rheopheresis has been found to be a safe and effective application of double filtration plasmapheresis (DFPP) for extracorporeal hemorheotherapy. In this report, it is proposed that Rheopheresis results in an immediate decrease in the proportion of high molecular weight proteins that could combine with the TIMP-3 fibulin complex allowing for the barely functioning retinal pigment epithelial (RPE) cells to function better and diminish the release of vascular endothelial growth factor (VEGF). Interim results from the randomized, double-masked MIRA-1 clinical trial include (1) improved vision restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200 vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's license qualification), compared to only 14.3% of Placebo Eyes 12-month post-treatment. Rheopheresis treatment shows strong promise as a viable clinical option for patients suffering from the dry form of AMD in terms of minimizing vision loss, vision restoration, and overall quality of life factors. Expanded clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the assessment of this new clinical tool for ophthalmic applications.

Calcium-Binding Proteins↗

Hematopoietic progenitor cell large volume leukapheresis (LVL) on the Fenwal Amicus blood separator.

A technique for large volume leukapheresis (LVL) for hematopoietic progenitor cell (HPC) collection using the Fenwal Amicus is presented. It was compared to standard collections (STD) with regard to CD34+ cell yields and cross-cellular content. Optimal cycle volumes and machine settings were evaluated for LVL procedures. A total of 68 patients underwent 80 HPC collection procedures. Because of differences in CD34+ cell yields associated with peripheral white blood cell counts (WBC), the comparison was divided into groups of 20 with WBC < or =35 x 10(9)/L (< or =35 K) and those >35 x 10(9)/L (>35 K). Baseline CD34+ cell counts (peripheral count when patient started HPC collection) were used (median 18-23 cells/microl). Significantly more whole blood (corrected for anticoagulant) was processed with LVL (LVL 20 l vs. STD 13.5 l). For < or =35 K, median CD34+ x 10(6), WBC x 10(9), RBC ml, Plt x 10(11) yields/collection were 183, 21.2, 14, 0.8, respectively, for STD vs. 307, 22.1, 11, 1.0, respectively, for LVL. For >35 K, median CD34+ x 10(6), WBC x 10(9), RBC ml, Plt x 10(11) yields/collection were 189, 32.7, 15, 1.4, respectively, for STD vs. 69, 40.8, 21, 1.3, respectively, for LVL. We have described a method of LVL using the Amicus that, in patients with pre-procedure WBC < or =35 x 10(9)/L, collects more CD34+ cells than a standard procedure with acceptable cross-cellular content. This method is not recommended when pre-procedure WBC counts are >35 x 10(9)/L.

Antigens, CD34↗

Paired comparison of Gambro Trima Accel versus Baxter Amicus single-needle plateletpheresis.

BACKGROUND: Gambro BCT recently introduced the Trima Accel Version 5 (TR) plateletpheresis machine. Platelet (PLT) yields, collection efficiencies (CEs), numbers of white blood cells (WBCs), and processing times of the TR versus the Amicus (Version 2.51) single-needle (AM) procedures were evaluated by use of a prospective paired comparison. STUDY DESIGN AND METHODS: Target yields of 3.0 x 10(11) to 6.8 x 10(11) PLTs in up to 100 minutes of processing time were used. To detect a difference of 1.0 x 10(11) PLTs with a power of 80 percent, 26 paired comparisons were needed. RESULTS: The mean amount of whole blood processed was significantly higher for TR than for AM (3795 vs. 3520 mL). The TR and AM were equivalent in regard to mean preprocedure PLT count (259 x 10(9) vs. 251 x 10(9)/L), PLT yields (6.7 x 10(11) vs. 6.5 x 10(11)), split rate (65% vs. 65%), processing time (73 vs. 78 min), and collection rate (0.090 x 10(11) vs. 0.084 x 10(11) PLTs/min). The TR had a significantly lower CE than the AM (76% vs. 86%). All of the products (after splitting) had fewer than 5 x 10(6) WBCs. CONCLUSIONS: The Trima Accel machine processed significantly more whole blood with equivalent PLT yields, processing time, and number of PLTs per minute compared to the Amicus single-needle procedure, but had a significantly lower CE.

Blood Donors↗

Transfusion of apheresis PLTs from IgA-deficient donors with anti-IgA is not associated with an increase in transfusion reactions.

BACKGROUND: Passive transfer of antibodies through transfusion has been reported to cause adverse consequences. Approximately 1 in 700 individuals of Northern European ancestry lack IgA with up to 40 percent reported as having anti-IgA. Whether these antibodies when passively transfused were associated with reactions was examined. STUDY DESIGN AND METHODS: Records were reviewed to identify IgA-deficient (<0.05 mg/dL detectable IgA) apheresis PLT donors with anti-IgA. Transfusion outcomes of products from these donors were compared to outcomes of control transfusions from donors who were not IgA-deficient. RESULTS: Four IgA-deficient donors with anti-IgA donated a total of 25 apheresis PLT products transfused to 22 recipients. Of the transfused products, 1 (4.0%) was associated with fever that was classified as unrelated to transfusion. In the control group, 60 donors donated 78 apheresis PLT products transfused to 56 recipients. Among these, an allergic reaction was identified (1.3%). The reaction rates between both groups were not different whether the single event in the anti-IgA group was considered a reaction (chi-squared value 0.735, p = 0.3914) or considered unrelated to transfusion (chi-square value 0.324, p = 0.5694). CONCLUSION: The transfusion of products containing anti-IgA does not appear to be associated with a greater frequency of reactions.

Adolescent↗

Frozen preoperative autologous blood donation for heart transplantation at the Mayo Clinic from 1988 to 1999.

BACKGROUND: Preoperative autologous blood donation (PABD) has been used to reduce the need for allogeneic RBC transfusion, decreasing risk and conserving supply. A frozen PABD program for heart transplant patients was instituted at the Mayo Clinic in 1988, but participation has steadily declined. The aims of this study were to determine how the availability of PABD influenced the transfusion RBC components, whether the availability of PABD reduced exposure to allogeneic RBC components, and the costs of providing PABD units. STUDY DESIGN AND METHODS: A retrospective review of all heart transplant cases from 1988 to 1999 was performed (n = 141). Data on collection and transfusion practices were compared for patients with (n = 88, 62%) and without PABD (n = 53, 38%). RESULTS: Total RBC transfusion requirements did not differ between the groups. Patients with frozen PABD received fewer allogeneic units, but they also had less blood salvaged and reinfused. Twenty patients (23%) completely avoided exposure to allogeneic RBCs in the PABD group versus three patients (6%) in the group without PABD. Although patients in the PABD group successfully donated a total of 423 units, 41 percent were discarded. Over 11 years, the need for 251 units of allogeneic RBCs was avoided ($27,610), but $283,500 was spent to have the frozen PABD units available. CONCLUSION: PABD can be performed for heart transplantation, but it is expensive.

Blood Preservation↗

Comparative performance of herpes simplex virus type 1-specific serologic assays from MRL and Meridian Diagnostics.

Two companies, MRL and Meridian Diagnostics, have developed Food and Drug Administration-approved herpes simplex virus type 1 type-specific enzyme immunoassays. The sensitivity, specificity, and overall testing efficiency of these assays were 98.2, 93.8, and 96.6% for MRL and 98.8, 99.0, and 98.1% for Meridian, making both of these kits suitable for use in the clinical lab.

Antibodies, Viral↗

State of the art treatment of the most difficult low density lipoprotein (LDL) cholesterol problems: LDL apheresis.

The patient benefit from reduction of an excessively elevated low density lipoprotein (LDL) cholesterol is now well established, especially when there is proven coronary atherosclerosis. Dietary adherence can lower LDL cholesterol by a maximum of 10% to 15%. The addition of a cholesterol-lowering medication frequently can achieve a major LDL cholesterol reduction. However, a small group of patients with a very high LDL cholesterol respond poorly to diet and pharmaceutical treatments. These same patients have the highest incidence for very premature coronary atherosclerosis and associated cardiac events. A few medical centers, including the University of Kentucky, have established a new program to benefit these difficult high-risk patients. The technique is known as LDL apheresis, an effective process for removal of LDL cholesterol. The procedure is highly effective but very costly and third-party approval barriers are preventing access to this essential treatment for some very high-risk coronary atherosclerosis patients.

Humans↗