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Biomedical subjects

S Breanndan Moore

Publications and source records attributed to S Breanndan Moore.

At least 19 recordsLinked to original sources

Acute graft-versus-host disease after liver transplantation diagnosed by fluorescent in situ hybridization testing of skin biopsy specimens.

Acute graft-versus-host disease after orthotopic liver transplantation is an underrecognized entity with a guarded prognosis. We describe a patient who underwent orthotopic liver transplantation with an HLA-matched donor liver. She had an uneventful recovery from operation up until day 36 posttransplantation, when she developed a generalized, erythematous, mostly macular eruption, accompanied by ascites, diarrhea, and fever. The diagnosis of graft-versus-host disease was considered but a drug rash could not be excluded. A polymerase chain reaction-based chimerism assay failed to identify donor DNA in peripheral blood. A confirmatory fluorescent in situ hybridization analysis revealed significant numbers of donor lymphocytes in biopsied skin, with lesser amounts in biopsy specimens from the stomach and colon. Despite immunosuppressive treatment, the patient died of overwhelming sepsis 18 weeks after transplantation. We conclude that early testing of skin biopsy specimens using fluorescent in situ hybridization in sex-mismatched patients with orthotopic liver transplantation can serve as an early diagnostic tool for graft-versus-host disease.

Acute Disease↗

Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis.

The term transfusion-related acute lung injury (TRALI) was coined in 1983 to describe a constellation of clinical and laboratory features seen within 6 hrs of the transfusion of plasma-containing blood products. These products contain antibodies directed to human leukocyte antigens (and subsequently described to nonhuman leukocyte antigens) found on white blood cells. In the intervening 2 decades, other cases not associated with antibodies have been reported as TRALI and an association with passive infusion of lipids accumulated in stored cellular blood products has been made in those cases. This has led to confusion as to what should be considered to constitute TRALI. Therefore, the true incidence of this pulmonary reaction to blood products is currently conjectural at best. Recent consensus development conferences have been held to develop and standardize definitions of TRALI so that epidemiologic and research aspects of this condition can be explored in a scientific manner. These conferences have set out criteria by which TRALI is distinguished from other causes of acute lung injury. This review outlines the widely accepted clinical (mainly pulmonary) features of TRALI, the treatment options, and the excellent long-term prognosis for patients who survive the initial pulmonary insult.

Humans↗

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↗

Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North American patients outside DR3 and DR4.

AIMS: To determine the clinical phenotype and outcome of patients with definite type 1 autoimmune hepatitis, who lack human leukocyte antigen (HLA) DR3 and DR4, and to assess the importance of HLA DR7 and DR13. METHODS: Two hundred and seven adult patients were typed for DR3, DR4, DR7, and DR13 by DNA-based techniques. One hundred and two blood donors constituted a normal population. RESULTS: Twenty-six patients lacked DR3 and DR4 (13%). Treatment failure occurred more commonly in these individuals than in the 68 patients with DR4 (20% vs. 3%, P = 0.03), and relapse after drug withdrawal was less frequent than in the 84 patients with DR3 (55% vs. 87%, P = 0.03). HLA DR13 occurred more often than in those with DR3 (54% vs. 15%, P = 0.0002) or DR4 (54% vs. 12%, P = 0.00005), and it was more frequent than in normal adults (54% vs. 22%, P = 0.003), including those without DR3 or DR4 (54% vs. 27%, P = 0.03). HLA DR7 was not associated with susceptibility or outcome. CONCLUSIONS: White North American patients who lack DR3 and DR4 respond differently to corticosteroid treatment than patients with classical HLA phenotypes. HLA DR13 is common in these adult patients, and it may affect treatment outcome.

Adrenal Cortex Hormones↗

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 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↗

A brief history of the early years of blood transfusion at the Mayo Clinic: the first blood bank in the United States (1935).

At the Mayo Clinic in 1914, Francis McGrath modified an existing aspiration-injection apparatus and adapted it for arm-to-arm blood transfusions. Separately, in 1919, both Pemberton and Sanford described in detail the Mayo Clinic experience with more than 1000 transfusions between January 1915 and January 1918. Most transfusions were by the indirect citrate method from freshly drawn blood. In 1935, John Lundy established a bank of refrigerated blood for transfusions at Mayo Clinic and reported on the activity in that and subsequent years. The functioning clinical blood bank established by Lundy at Mayo Clinic predated that of Bernard Fantus in Chicago by almost 2 years.

Blood Banks↗

Transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is characterized by the sudden development of noncardlogenic pulmonary edema (acute lung Injury) after transfusion of blood products. Poor awareness of TRALI outside of the blood transfusion medicine community has led to a serious underestimation of this condition, currently the most Important severe complication of blood transfusion. Concern for the transfer of donor antileukocyte antibodies has prompted major changes in the management of the blood supply in some countries; however, recent studies have suggested alternative pathophyslological mechanisms for TRALI related to the shelf life of cellular blood products. Although all blood products have been implicated, most reported cases were associated with fresh frozen plasma, red blood cell, and platelet transfusions. Because many patients have additional predisposing factors for acute lung injury, carefully designed prospective studies are needed to fully assess attributable risk related to transfusion. The treatment of TRALI is supportive, and the prognosis is generally better than for other causes of acute lung Injury. As many as one third of all patients who develop acute lung injury have been exposed to blood products. TRALI may be an important and potentially preventable cause of acute lung injury.

Global Health↗

Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy.

OBJECTIVE: Although restrictive red cell transfusion practice has become a standard of care in the critically ill, data on the use of fresh frozen plasma (FFP) are limited. We hypothesized that the practice of FFP transfusion in the medical intensive care unit is variable and that liberal use may not be associated with improved outcome. DESIGN: Retrospective cohort study. SETTING: A 24-bed medical intensive care unit in a tertiary referral center. PATIENTS: All patients admitted to a medical intensive care unit during a 5-month period who had abnormal coagulation defined as international normalized ratio (INR) of > or = 1.5-times normal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected data on demographics, severity of illness as measured by Acute Physiology and Chronic Health Evaluation (APACHE) III scores, INR, bleeding episodes, and transfusion complications. We identified 115 patients with coagulopathy (INR of > or = 1.5) but without active bleeding. A total of 44 patients (38.3%) received FFP transfusion. INR was corrected in 16 of 44 patients (36%) who received transfusion. Median dose of FFP was 17 mL/kg in patients who had INR corrected vs. 10 mL/kg in those who did not (p = .018). There was no difference in age, sex, APACHE III scores, liver disease, Coumadin treatment, or INR level between those who did and did not receive FFP. Invasive procedures (68.2% vs. 40.8%, p = .004) and history of recent gastrointestinal bleeding (41% vs. 7%, p < .001) were more frequent in the group with transfusion. Although there was no difference in new bleeding episodes (6.8% in transfused vs. 2.8% in nontransfused group, p = .369), new onset acute lung injury was more frequent in the transfused group (18% vs. 4%, p = .021). Adjusted for severity of illness, hospital mortality and intensive care unit length of stay among survivors were not different between the two groups. CONCLUSION: The risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable. Randomized controlled trials evaluating restrictive vs. liberal FFP transfusion strategies are warranted.

APACHE↗

Quality school: an innovative approach to laboratory quality practices training.

The quality management program in the Division of Transfusion Medicine at our institution had evolved to the point that the program generally was perceived to be the sole responsibility of our Quality Unit (which was administratively independent of day-to-day operations). It became clear that this administrative model was counterproductive to our new goal of instilling a responsibility for quality into every work level of our division. Such a culture change requires a considerable, organized educational effort. Quality School was established to meet these particular educational needs. The details of the modular structure of the courses and the initial results of their implementation are described. This Quality School approach was developed specifically for transfusion medicine, but the principles could be applied to any clinical laboratory.

Blood Banks↗

Persistence of low levels of alloantibody after desensitization in crossmatch-positive living-donor kidney transplantation.

BACKGROUND: : Desensitization protocols have been developed to allow successful kidney transplantation in sensitized recipients. However, a detailed analysis of the impact of these protocols on alloantibody has not been performed. METHODS: : We studied 12 living-donor kidney-transplant recipients with positive antihuman globulin-enhanced complement dependent cytotoxicity (AHG-CDC) crossmatches against their donors. Using a variety of crossmatch techniques and single-antigen flowbeads (SAFBs), we characterized the specificity and amount of alloantibody at baseline before desensitization, after desensitization (using plasmapheresis followed by 100 mg/kg intravenous immunoglobulin, and anti-CD20 antibody), and 4 months after transplantation (after splenectomy and on maintenance immunosuppression). RESULTS: : All 12 patients with a positive baseline AHG-CDC crossmatch were AHG-CDC crossmatch negative at the time of transplant (after desensitization). However, despite desensitization, the majority of patients had low-level donor-specific alloantibodies demonstrable on the day of transplantation by both flow crossmatch (FXM 8/12) and SAFBs (10/11). Four months after transplantation, no patient had a positive AHG-CDC crossmatch, but again the majority had persistent low levels of donor-specific alloantibodies by FXM (6/12) and SAFBs (9/11). No patient experienced hyperacute rejection, and the persistence of low levels of donor-specific alloantibodies did not correlate with the development of humoral rejection in the early posttransplant period. CONCLUSIONS: : Despite desensitization, a majority of positive crossmatch transplant recipients demonstrate low levels of donor-specific alloantibodies both on the day of transplant and 4 months after transplantation. The impact of these antibodies appears to be minimal early after transplant, but their long-term significance bears further study.

B-Lymphocytes↗

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↗

Acute lung injury after blood transfusion in mechanically ventilated patients.

BACKGROUND: Liberal transfusion strategy increases the risk of acute lung injury (ALI), but specific transfusion-related factors have not been characterized. We tested the hypotheses that storage age and specific type of blood products are associated with increased risk of ALI in mechanically ventilated patients. STUDY DESIGN AND METHODS: From a database of mechanically ventilated patients, we identified those who received blood products during the first 48 hours of intensive care. We extracted information about underlying ALI risk factors as well as the type, amount, and shelf age of administered blood products. Outcome was assessed by an independent, blind review of chest radiographs and clinical findings. RESULTS: Of 181 patients transfused during the first 48 hours of mechanical ventilation, 60 (33%) developed ALI. There was no difference in average duration of red blood cells storage between patients who did and did not develop ALI (median, 18.5 vs. 17.5 days; p = 0.22). In a multivariable logistic regression analysis, important risk factors associated with the development of ALI were thrombocytopenia (odds ratio, 5.9; p = 0.004) and transfusion of fresh frozen plasma (odds ratio, 3.2; p = 0.023). CONCLUSION: Thrombocytopenia and transfusion of fresh frozen plasma, but not storage age of red blood cells, were associated with the development of ALI in this cohort of mechanically ventilated patients.

Aged↗

ABO-incompatible kidney transplantation using both A2 and non-A2 living donors.

BACKGROUND: Given the scarcity of cadaveric organs, efforts are intensifying to increase the availability of living donors. The current study assessed the feasibility of using ABO-incompatible living-donor kidneys to expand the donor pool. METHODS: The authors performed 18 ABO-incompatible living-donor kidney transplants between May 1999 and April 2001. Ten patients received living-donor kidneys from A2 and eight patients received kidneys from non-A2 blood group donors. Immunosuppression consisted of Thymoglobulin antibody induction, tacrolimus, mycophenolate mofetil, and prednisone. Eight non-A2 and two A2 kidney recipients also received a pretransplant conditioning regimen of four plasmapheresis treatments followed by intravenous immunoglobulin and splenectomy at the time of transplantation. Antidonor blood group antibody titer was measured at baseline, pretransplant, at 1- to 3-month and 1-year follow-up, and at the time of diagnosis of antibody-mediated rejection. RESULTS: No hyperacute rejection episodes occurred. One-year graft and patient survival rates in the 18 ABO-incompatible recipients were only slightly lower than those of 81 patients who received ABO-compatible kidney transplants during the same period (89% vs. 96% and 94% vs. 99%, respectively). Glomerular filtration rate and serum creatinine levels did not differ between the groups. Antibody-mediated rejection occurred in 28% of ABO-incompatible recipients, and was reversible with plasmapheresis, intravenous immunoglobulin, and increasing immunosuppression in all patients except one. CONCLUSIONS: ABO-incompatible living donor kidney transplants can achieve an acceptable 1-year graft survival rate using an immunosuppressive regimen consisting of Thymoglobulin induction, tacrolimus, mycophenolate mofetil, and prednisone combined with pretransplant plasmapheresis, intravenous immunoglobulin, and splenectomy.

ABO Blood-Group System↗

The association of class I HLA alleles and antibody levels after a single dose of measles vaccine.

Despite the success of the current measles vaccine in controlling disease in industrialized countries, the importance of vaccine failure has become increasingly apparent. Our objective was to determine if associations exist between seronegativity after measles vaccination and class I human leukocyte antigen (HLA) alleles. We undertook a cross-sectional observational study in Rochester, Minnesota, with 242 school-age children previously recruited from a communitywide seroprevalence study. We studied two groups of subjects: 72 were seronegative (EIA < or =0.8 after a single dose of measles vaccine) and 170 were seropositive (enzyme immunoassy [EIA] > or =1.0 after one dose). We used the resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A and HLA-B alleles via microlymphocytotoxicity assays. We found no statistically significant associations with class I HLA-A but did find associations with class I HLA-B, which includes alleles associated with seronegativity (B8, B13, and B44) and those associated with seropositivity (B7 and B51). Elucidation of the specific peptide-HLA complex interactions that lead to varying or failed immune responses may provide fertile groundwork for improved vaccines that can overcome limitations of the current live, attenuated measles vaccine.

Alleles↗

Overcoming a positive crossmatch in living-donor kidney transplantation.

Many patients who have an otherwise acceptable living-kidney donor do not undergo transplantation because of the presence of antibodies against the donor cells resulting in a positive crossmatch. In the current study, 14 patients with a positive cytotoxic crossmatch (titer </= 1 : 16) against their living donor underwent a regimen including pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Eleven of 14 grafts (79%) are functioning well 30-600 days after transplantation. Two grafts were lost to accelerated vasculopathy and one was lost to death with good function. No hyperacute or cellular rejections occurred. Antibody-mediated rejection occurred in six patients [two clinical (14%) and four subclinical (29%)] and was reversible with plasmapheresis and steroids. Our results suggest that selected crossmatch-positive patients can be transplanted successfully with living-donor kidney allografts, using a protocol of pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Longer follow-up will be needed, but the absence of anti-donor antibody and good early outcomes are encouraging.

Adult↗