Search

Recognized principles of quality management include a component for process improvement, comprised largely of corrective and preventive action taken in response to identified problems. The importance of identifying and investigating problems has been clearly established in transfusion medicine. Such problems can be identified in the following ways: error, incident, and accident reports; adverse reaction reports; customer complaints; process indicator measurements; results of proficiency testing; and results of internal or external audits, inspections, or assessments. Responses to reported events can be remedial, in which the symptom is addressed, or corrective, in which the underlying cause is addressed with the intent to prevent recurrence. If identified problems or their root causes are trended to look for patterns or problems not yet occurring are anticipated, the action taken is proactive and considered preventive. Methods to trend events, monitor processes, and perform root cause analysis are discussed as well as use of the following process improvement 'tools': control charts, flowcharting, the 'repetitive why', cause-and-effect diagram, and Pareto analysis.

While the Moraten strain measles vaccine is an excellent, safe, and immunogenic vaccine, vaccine failure occurs, presumably when an individual develops an inadequate immune response. In this study, we examined the association of HLA class I genes and measles vaccine-induced antibody levels. We found that the allele distribution of HLA-B alleles differed between non-responders and hyper-responders (p = 0.002). Several class I alleles were associated with non-response (HLA-B13, -B44, and -C5); whereas several other alleles were associated with hyper-response (HLA-B7 and -B51). In addition, non-responders were more likely to be HLA-B homozygous than normal responders (odds ratio 2.1), and more likely to be homozygous than hyper-responders (odds ratio 3.7, p = 0.031 Mantel-Haenzel for trend). Finally, we found evidence of an allele dose-response phenomenon for HLA-B7. We conclude that there are important associations between class I HLA genes and measles antibody levels following immunization.

Immune disorders in chronic liver disease may reflect common host propensities or disease-specific factors. Our aim was to determine the principal bases for these expressions. Four hundred fifty-one patients with various chronic liver diseases were assessed prospectively for concurrent immune disorders. Individuals with immune diseases were more frequently women (73% vs 60%, P = 0.02) and they had HLA DR4 more often than counterparts with other HLA (46% vs 23%, P = 0.000008). The association between HLA DR4 and immune disease was apparent within individual liver diseases and within different categories of liver disease. Women with HLA DR4 had a higher frequency of immune disease than women without HLA DR4 (52% vs 22%, P < or = 0.000001), and they also had immune diseases more commonly than DR4-positive men (52% vs 31%, P = 0.03). DR4-positive men, however, had higher frequencies of immune disease than DR4-negative men, especially in the nonimmune types of liver disease (26% vs 4%, P = 0.002). We conclude that HLA DR4 and female gender constitute an immune phenotype that is an important basis for autoimmune expression in chronic liver disease.

Background: The major histocompatibility complex (MHC) has been consistently associated with susceptibility to MS and the course of several other human autoimmune diseases. A putative association between the course and severity of MS and the MHC remains controversial., Methods: DR and DQ genotyping by either restriction fragment length polymorphism or sequence-specific PCR-based typing in 119 patients representing 73.4% of the population with MS evaluated in a cross-sectional disability survey and 100 healthy controls from Olmsted County, Minnesota., Results: We found a positive association between MS susceptibility and the DR15-DQ6 and DR13-DQ7 haplotypes, and we found a negative association with the DR1-DQ5 haplotype. We found a trend to a positive association of primary progressive MS with DR4-DQ8 and DR1-DQ5 and an association of "bout onset" MS with DR17-DQ2. We did not find an association with disease severity, as defined by EDSS/duration., Conclusion: Lack of consistency between different studies may be due to regional variation in MS and limitations of power but likely indicate a minor effect of MHC class II genes on the course and severity of MS.

Background/aim: Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence., Methods: Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were made with 41 patients who had nonalcoholic steatohepatitis and 18 patients who had chronic hepatitis B., Results: Patients with chronic hepatitis C and steatosis had lower serum concentrations of gamma-globulin (p=0.01) and immunoglobulin G (p=0.05) than their counterparts without steatosis, and they had a lower frequency of antinuclear antibodies (19% versus 52%, p=0.01). They also had a higher mean body mass index (p=0.002) and a greater frequency of risk factors for steatosis (70% versus 34%, p=0.009). These risk factors, however, occurred more commonly in patients with nonalcoholic steatosis (p=0.007). Furthermore, fat deposition occurred more often in chronic hepatitis C than in chronic hepatitis B (52% versus 22%, p=0.03), despite comparable metabolic findings. The degree of steatosis in chronic hepatitis C was not associated with individual metabolic features., Conclusions: Steatosis in chronic hepatitis C is mainly a viral effect, and host-dependent metabolic factors may potentiate the manifestation. Fat deposition is associated with less immunoreactivity and it may connote a distinctive pathogenic mechanism.

We compared the ability of solid-phase enzyme immunoassay (SPEIA) with that of indirect immunofluorescence to detect serum platelet antibodies by parallel testing five sets of serum specimens: (1) 12 monospecific HLA class I specimens with defined specificities, (2) 4 HPA-1a specimens, (3) 164 sequential unselected specimens sent to our laboratory for serum platelet antibody testing, (4) specimens from 15 consecutive patients sent for indirect immunofluorescence testing alone, and (5) specimens from 19 consecutive patients sent for both indirect and direct immunofluorescence testing. In addition, specimens of HLA sera were tested by standard complement-dependent lymphocytotoxicity. Solid-phase enzyme immunoassay was consistently more sensitive than indirect immunofluorescence for all 12 HLA specimens and more sensitive than complement-dependent lymphocytotoxicity for 11 of 12 specimens. Similarly, SPEIA was more sensitive than indirect immunofluorescence for all four HPA-1a serum specimens by one to three dilutions. In the nine presumed autoimmune cases (group 5), results were positive with SPEIA in one case; no positive results were noted with indirect immunofluorescence. The solid-phase enzyme immunoassay test permits ready differentiation between alloantibodies directed to HLA and those directed to platelet-specific glycoproteins.

Background: IgG antibodies to HLA class I antigens can cause hyperacute rejection of renal allografts. Screening of sera from such transplant candidates is laborious, time-consuming, and expensive when performed by sensitive antihuman globulin-augmented lymphocytotoxicity (AHG-CDC)., Methods: Because 60-70% of our transplant screens are negative, we evaluated a solid phase enzyme-linked method (EIA) as a potential prescreen by parallel testing 215 sera by AHG-CDC and by EIA. This EIA method is designed to detect only IgG antibodies, and all positive AHG-CDC sera were retested after dithiothreitol treatment., Results: There was 96.2% concordance between the tests for IgG antibodies. Seven sera (3.25%) were positive by EIA alone, and one (0.46%) was negative by EIA alone. The EIA method was also less costly ($15.00 versus $105.00) and less time consuming (hours versus days) than AHG-CDC panel testing for large numbers of sera., Conclusions: We conclude that this EIA method is simple, sensitive, objective, and cost effective as a prescreen for HLA class I antibodies.

Objectives: Our aim was to determine whether alleles affecting susceptibility to type 1 autoimmune hepatitis in the United States occur as commonly in German patients with type 2 disease., Methods: DNA specimens from 12 German patients with type 2 autoimmune hepatitis were tested for class II alleles of the major histocompatibility complex by polymerase chain reaction using sequence specific primers. Eighty-six American patients with type 1 disease and 102 Caucasoid normal subjects from the United States were tested in a similar manner., Results: American patients with type 1 autoimmune hepatitis had DRB1*03 alleles more commonly than the German patients with type 2 disease (51% vs 17%, p = 0.03) and DRB1*0301 occurred more frequently in the type 1 patients (51% vs 17%, p = 0.03). The frequency of DRB1*04 alleles was also higher in the type 1 patients after exclusion of the DR1*03 alleles (64% vs 20%, p = 0.01). In contrast, patients with type 2 disease more commonly had DRB1*07 (p = 0.003), DRB1*15 (p = 0.004), and DQB1*06 (p = 0.0004). DRB1*07 (p = 0.005), DRB4*01 (p = 0.03), and DQB1*06 (p = 0.03) also occurred more frequently in the type 2 patients from Germany than in the normal subjects from the United States, although none of these frequencies were statistically significant by an adjusted p value., Conclusions: German patients with type 2 autoimmune hepatitis do not have the same susceptibility alleles as American patients with type 1 disease. Regional differences in prevalence may reflect the genetic profiles of the populations at risk.

To describe the post-transfusion survival of an entire, geographically defined population, we observed all residents of a US county who underwent perioperative transfusion before and after the introduction of a large autologous transfusion programme. We enrolled 444 and 1540 county residents, transfused in 1981 and in 1986-88, respectively. Complete follow-up (until death or for 5 years) was available on 1960 patients (98.8%). Of patients transfused in 1986-88, 67.6% were alive at 5 years, having survived for a mean (+/- SE) period of 46.15 (+/- 0.575) months. The survival statistics were 66.2% and 46.09 (+/- 1.047) months, respectively, for patients transfused in 1981 (P = 0.8424). Transfusion in 1986-88 vs. 1981 (with 615 [40%] vs. six [1.3%] patients receiving some autologous blood) did not have an effect on survival (P = 0.3892), following adjustment for age, gender, transfusion dose, receipt of a single-unit transfusion and transfusing surgical service. We conclude that the survival of an entire, geographically defined transfused population is substantially longer than that reported previously for patients referred to tertiary-care medical centres. The aggregate 5-year survival of patients transfused in 1981 and in 1986-88 does not differ, despite differences in patient case-mix and in perioperative transfusion practice, particularly as it relates to autologous blood usage.

As a potential novel approach to preventing renal allograft rejection, we investigated whether the proliferative response of lymphocytes to mismatched HLA class II antigens in mixed lymphocytic culture (MLC) can be suppressed by antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes. Cilostamide, an antagonist of isozyme PDE3 and, to an even greater extent, in combination with rolipram, an antagonist of isozyme PDE4, markedly suppressed (delta = -60%; p < 0.01) the mitogenic proliferative response of lymphocytes in MLC to HLA-DR alloantigens from unrelated donors. These observations suggest that the selective PDE isozyme antagonists might have potential as novel drugs in "signal transduction-targeted" pharmacotherapy of renal transplant rejection.

We report the case of a 24-year-old man who received high-dose cyclophosphamide (CY) 120 mg/kg over 2 days and twice daily fractionated total body irradiation (TBI) over 3 days(1,320 cGy) prior to allogeneic bone marrow transplantation. Seven and one-half years later he fathered a normal child who has developed normally so far.

Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103, whereas the DRB1*1501 allele may protect from the disease. Our aim was to determine if these alleles or others influence clinical manifestations and prognosis. Eighty-six white patients were evaluated prospectively for immune features and outcomes. Class I alleles were determined by microlymphocytotoxicity, and class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes or sequence-specific primers. One hundred two white, normal subjects were typed in the same fashion. Patients with concurrent immunologic diseases were more commonly positive for DRB4*0103 than patients without these features (68% vs. 38%, P = .01). DRB1*0301 (86% vs. 45%, P = .008) and the DRB1*0301-DRB3*0101 haplotype (79% vs. 42%, P = .02) occurred more commonly in patients who deteriorated during corticosteroid therapy. In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 haplotype were associated with a lower frequency of death from liver failure or the need for transplantation than patients with other alleles (0% vs. 37%, P = .03). Patients with DRB1*0301 differed from those with DRB1*0401 in that they were younger and failed treatment more commonly (27% vs. 5%, P = .04). We conclude that alleles associated with susceptibility to type 1 autoimmune hepatitis also influence its clinical features and prognosis. DRB4*0103 is associated with concurrent immune diseases, DRB1*0301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation.

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

Error management plays a major role in facility process improvement efforts. By detecting and reducing errors, quality and, therefore, patient care improve. It begins with a strong organizational foundation of management attitude with clear, consistent employee direction and appropriate physical facilities. Clearly defined critical processes, critical activities, and SOPs act as the framework for operations as well as active quality monitoring. To assure that personnel can detect an report errors they must be trained in both operational duties and error management practices. Use of simulated/intentional errors and incorporation of error detection into competency assessment keeps employees practiced, confident, and diminishes fear of the unknown. Personnel can clearly see that errors are indeed used as opportunities for process improvement and not for punishment. The facility must have a clearly defined and consistently used definition for reportable errors. Reportable errors should include those errors with potentially harmful outcomes as well as those errors that are "upstream," and thus further away from the outcome. A well-written error report consists of who, what, when, where, why/how, and follow-up to the error. Before correction can occur, an investigation to determine the underlying cause of the error should be undertaken. Obviously, the best corrective action is prevention. Correction can occur at five different levels; however, only three of these levels are directed at prevention. Prevention requires a method to collect and analyze data concerning errors. In the authors' facility a functional error classification method and a quality system-based classification have been useful. An active method to search for problems uncovers them further upstream, before they can have disastrous outcomes. In the continual quest for improving processes, an error management program is itself a process that needs improvement, and we must strive to always close the circle of quality assurance. Ultimately, the goal of better patient care will be the reward.

A 67-year-old man with Waldenström's macroglobulinemia had a relapse of chronic idiopathic thrombocytopenic purpura (ITP), which had been refractory to corticosteroids, splenectomy, vinca alkaloids, and high-dose intravenous gamma-globulin therapy. A biclonal gammopathy (IgM kappa and IgG lambda) was detected in his serum and was likely responsible for his refractory thrombocytopenia. He was treated with chlorambucil and prednisone. Plasmapheresis was effective in temporarily maintaining platelet counts and in decreasing morbidity until immunosuppression was completely effective against the production of the monoclonal protein. The previously reported experiences with use of plasmapheresis in patients with chronic ITP are discussed. Plasmapheresis may be of value in the treatment of selected patients with severe ITP and monoclonal gammopathy.

Background/aims: Immune mechanisms may modulate disease severity in chronic hepatitis C and the DR human leukocyte antigens may affect these mechanisms. Our aims were to evaluate the association between the DR antigens and disease severity at presentation and to seek correlation between these antigens, disease severity and autoantibodies in this condition., Methods: Sixty-four patients were assessed prospectively and classified as having mild, moderate and severe disease by clinical, laboratory and histologic criteria. Fourteen DR antigens were determined by restriction fragment length polymorphism or polymerase chain reaction-sequence specific primers. Eighty normal subjects were typed in a similar fashion., Results: Patients with mild (16), moderate (32) and severe (16) disease at presentation were indistinguishable from each other and from normal subjects by the frequencies of each DR antigen. Subsets of patients with different laboratory and histological findings had DR frequencies comparable to those without these findings and to those of normal subjects. Patients with autoantibodies and/or concurrent immunologic diseases had mild (19% versus 32%, p = 0.4), moderate (50% versus 50%) and severe (31% versus 18%, p = 0.4) disease as commonly as other patients. The frequencies of the DR antigens were similar in each category of disease severity. Patients with autoimmune features differed from patients without these features (3% versus 32%, p = 0.002) and normal subjects (3% versus 25%, p = 0.003) by having a lower frequency of HLA DR1., Conclusions: The DR antigens are not associated with any index of disease severity at presentation. Immunologic manifestations do not identify patients with a different disease severity or a distinctive genetic predisposition for disease activity. The presence of DR 1 is associated with a lower frequency of immune manifestations.

Background/aims: Human leukocyte antigens DR3 and DR4 influence susceptibility for type 1 autoimmune hepatitis and affect its immunological manifestations. We aimed to determine if autoimmune features in patients with chronic liver diseases other than autoimmune hepatitis are associated with these same antigens., Methods: One hundred and seventy-eight patients were evaluated. Class II typing was performed by restriction fragment length polymorphism in all patients and 80 normal subjects., Results: One or more autoantibodies, including antinuclear antibodies (28%), smooth muscle antibodies (8%), thyroid antibodies (18%) and antimitochondrial antibodies (13%), were found in 92 patients (52%). Concurrent clinical diseases of an immunological nature were recognized in 53 patients (30%). Patients with antinuclear antibodies had a higher frequency of the A1-B8-DR3 haplotype than patients without these antibodies (27% versus 12%, p = 0.04) and patients with concurrent immunological diseases had a higher frequency of HLA DR4 than patients without this antigen (51% versus 26%, p = 0.003). Patients with antinuclear antibodies were more commonly DR3 positive than normals (35% versus 16%, p = 0.03) and patients with concurrent immunological diseases were more commonly HLA DR4 positive than normals (51% versus 30%, p = 0.02)., Conclusions: We conclude that the clinical expression of antinuclear antibodies is associated with the A1-B8-DR3 haplotype and the presence of concurrent immunological diseases is related to the DR4 antigen. These clinical manifestations have a genetic basis that is not disease-specific.

Forces influencing the composition of the mature TCR repertoire have been well studied in the mouse. In particular, the contribution of MHC molecules in negative and positive selection events of T lymphocytes has been established. To understand whether the allelic polymorphism of HLA-DRB1 molecules can shape the human TCR repertoire, we compared the usage of TCR V beta segments in two cohorts of unrelated individuals who were selected for the expression of HLA-DRB1 alleles. To investigate the potential role of antigenic experience in shaping the TCR repertoire, we compared the usage of V beta gene elements in CD45RO- CD4+ (naive) T cells versus CD45RO+ CD4+ (memory) T cells. A correlation between V beta gene segment usage and HLA-DRB1 alleles could be demonstrated for the repertoire of the naive CD4+ T cells, suggesting a shaping force of the HLA-DRB1 allele on the peripheral TCR repertoire. While the HLA-DRB1 imposed profile in V beta distribution was maintained in CD45RO+ CD4+ T cells, it was less pronounced, indicating that antigenic experience modulates the functional TCR repertoire.

Objective: To determine whether, in patients with type 1 autoimmune hepatitis and human leukocyte antigen (HLA) DR3 and DR4 positivity, any DQ antigen is disease-specific., Material and Methods: HLA class II typing was performed by restriction fragment length polymorphism in 103 patients with type 1 autoimmune hepatitis, 104 patients with chronic viral hepatitis, and 80 normal subjects. A shared association with a disease-specific DQ antigen was sought in patients with HLA-DR3, DR4, and DR3-DR4., Results: Patients with HLA-DR3 and DR4 shared positivity for DQ2, DQ4, DQ5, DQ6, and DQ7, but the associations reflected established linkages or were of low frequency. Patients heterozygous for DR3-DR4 or homozygous for either DR3 or DR4 did not have a shared DQ antigen. Only the DR3-DQ2 haplotype distinguished patients with autoimmune hepatitis from normal subjects or those with chronic viral hepatitis., Conclusion: The DR3 and DR4 antigens are not associated with a single disease-specific DQ antigen in type 1 autoimmune hepatitis. The DR3-DQ2 haplotype is the principal risk factor for the disease at our referral center. Analyses by restriction fragment length polymorphism do not implicate a single susceptibility gene at the DQ locus.

Objective: To determine disease concordancy in the first identical twin with corticobasal degeneration. The patients were 63-year-old, erythrocyte antigen-confirmed monozygotic male twins who were clinically discordant for progressive apraxia caused by corticobasal degeneration., Interventions: Neuropsychologic and kinesiologic testing, magnetic resonance imaging, and positron emission tomographic measurements of cerebral metabolic rate for glucose., Results: The affected twin had lower neuropsychologic and kinesiologic test scores than did his brother, particularly on tests sensitive to right-compared with left-hemisphere function; widespread cerebral atrophy, worst in right parietotemporal cortices; and reduced whole-brain cerebral metabolic rate for glucose, worst in right posterior cortices. The clinically asymptomatic twin had normal neuropsychologic and kinesiologic test scores but performed more poorly on tests sensitive to left- compared with right-hemisphere function; had no abnormalities on magnetic resonance imaging; and had left temporoparietal as well as mild whole-brain hypometabolism., Conclusions: Corticobasal degeneration may remain clinically discordant in identical twins after 7 years. Positron emission tomography and neuropsychologic findings suggest the possibility of a preclinical stage of corticobasal degeneration. There is generalized cortical atrophy in patients with corticobasal degeneration in addition to focal atrophy.

Immune mechanisms have been implicated in chronic viral hepatitis, and these may be influenced by genetic factors. To determine if disease severity in chronic viral hepatitis is associated with the human leukocyte antigens DR3 and/or DR4, 109 patients were evaluated prospectively. The frequencies of DR3 and DR4 in these patients were compared to those in 80 normal subjects. Patients with DR3 and/or DR4 had the same occurrence of severe disease as patients with other DR antigens (21% versus 30%, P = 0.3). Patients with DR3, however, had higher serum gamma globulin and immunoglobulin G levels than patients with DR4 and a greater frequency of severe disease (36% vs 12%, P = 0.046). Patients with DR4 had concurrent immunologic diseases more commonly than patients with DR3 (44% vs 9%, P = 0.005) and patients with other DR antigens (44% vs 9%, P = 0.0002). Patients with DR4 but not DR3 had severe disease less frequently than other patients (9% vs 31%, P = 0.02). The frequencies of DR3 in patients with severe disease (37% vs 18%, P = 0.06) and DR4 in patients without severe disease (44% vs 30%, P = 0.07) were different than those in normal subjects but not to a statistically significant level. We conclude that patients with DR3 and DR4 have different clinical and laboratory findings and disease severity. Patients with DR4 have milder disease than patients with other DR antigens. Disease severity, however, is not closely associated with DR3 or DR4.

Background/aims: Chronic viral hepatitis may have immunologic manifestations, and such features may reflect genetic predispositions. The aim of this study was to assess associations between immune manifestations and HLA-DR antigens., Methods: Ninety-five patients were evaluated prospectively for immunologic features. A microlymphocytotoxicity technique was used to determine DR3, DR4, and A1-B8-DR3 phenotypes. DR antigens were also determined by restriction fragment length polymorphism in 76 patients with chronic viral hepatitis and 80 normal subjects., Results: Autoantibodies were found in 59 patients (62%), and concurrent immunologic diseases were found in 22 patients (23%). Patients with antinuclear antibodies had the A1-B8-DR3 phenotype more commonly than seronegative counterparts (26% vs. 6%; P = 0.02) and had DR3 positivity more frequently than normal subjects (41% vs. 18%; P = 0.03). In contrast, patients with concurrent immunologic diseases had DR4 positivity more commonly than patients without these findings (68% vs. 27%; P = 0.001) and normal subjects (68% vs. 30%; P = 0.003)., Conclusions: Patients with chronic viral hepatitis commonly have autoantibodies and/or concurrent immunologic diseases. The expression of antinuclear antibodies is associated with the A1-B8-DR3 phenotype, and the presence of concurrent immunologic diseases is associated with the DR4 phenotype. In these instances, autoimmune expression may reflect a genetic predisposition that is facilitated by viral infection or is coincidental with it.

Objective: To calculate the total "potential" frequency of preoperatively donated autologous erythrocyte (red blood cell or RBC) units in the entire population of patients who received transfusions in a specific US county, in a hypothetical situation in which all patients who received transfusions for elective surgical procedures (and were considered medically eligible for preoperative autologous blood donation [PABD]) predeposited a number of autologous RBCs appropriate for their procedure., Material and Methods: All Olmsted County residents who received RBC transfusions during 1991 and 1992 were retrospectively assessed for eligibility for PABD. Patients who were eligible to donate blood were assigned a number of autologous RBC predeposits appropriate for their scheduled procedure. Calculated total potential frequency figures for PABD were compared statistically on the basis of age, gender, and surgical service., Results: Study patients were eligible for PABD in 459 of 1,038 surgical admissions. The percentage eligibility for PABD was similar across age and gender patient groups but differed across admitting surgical services. Reasons for ineligibility for PABD differed across the patient categories studied. Under the aforementioned assumption, theoretically 786 of the 8,137 RBC units transfused to all study patients (9.7%) could have been provided by PABD., Conclusion: From the standpoint of an entire community population, the total potential effect of PABD on the blood supply can amount to a maximum of 9.7% of all transfused units of RBCs, an upper limit that is similar across age and gender patient groups but differs across transfusing surgical services.

Objective: To determine the effect of perioperative blood transfusions in patients with prostate cancer who underwent radical prostatectomy, we analyzed 1,785 patients with a follow-up of five years or more who were treated during a twenty-one-year period (1966 to 1987)., Methods: Patients were divided into three groups according to the number of units transfused during the perioperative period: group 1, 0 units (n = 440), group 2, 1 to 2 units (n = 746), and group 3, 3 or more units (n = 599)., Results: With univariate analysis, no statistically significant differences were found among the three groups in overall survival rate (71%, 75%, and 71% at ten years; p = 0.48), cause-specific survival rate (89%, 88%, and 86% at ten years; p = 0.36), or progression-free survival rate (61%, 68%, and 68% at ten years; p = 0.83). Adjusting for tumor grade, pathologic stage, and hormonal therapy using the Cox statistical model, we found no significant association between the blood-use group and overall survival rate (p = 0.45), cause-specific survival rate (p = 0.17), or progression-free survival rate (p = 0.34). The estimated relative risk and 95 percent confidence interval associated with blood transfusion (three or more units versus none) were as follows: 1.03 and 0.76 to 1.38 for total mortality, 1.56 and 0.95 to 2.56 for cause-specific death, and 1.20 and 0.91 to 1.57 for disease progression, respectively., Conclusions: According to these findings, withholding homologous blood transfusion, except for infectious precautions, should not be based on the suspicion that it can accelerate death from cancer in patients who undergo radical prostatectomy for prostate cancer.

Spontaneous echo contrast ("echocardiographic smoke") is known to occur in low-flow states and to require the presence of red cells and plasma proteins. Limited morphologic information regarding the microanatomic structure of red cells exhibiting spontaneous echo contrast is known. The study was designed to evaluate the microanatomic features of red cells exhibiting spontaneous echocardiographic contrast with scanning electron microscopy. With human blood, a beaker, and a stirring bar, a simple model for demonstration of spontaneous echo contrast and its reversal was devised. Blood elements were "sampled" from within this model at times of high and low spontaneous echogenicity by adherence of blood elements to poly-L-lysine-coated slides that were subsequently fixed and examined with scanning electron microscopy. Spontaneous echo contrast was maximal at complete stasis or low-flow states and could be abolished by agitation of blood with continuous stirring. Sampling during low-flow states with high echogenicity showed a preponderance of clumped red cells, whereas at high-flow and low echogenicity states red cells were dispersed and usually solitary. No morphologic features suggestive of activation of the coagulation system were noted. Spontaneous echo contrast is caused by reversible red blood cell clumping, which occurs in fresh human blood at low-flow (low shear rate) states and can be abolished by increasing flow. This phenomenon is independent of activation of the clotting system.

Background: HLA DR3 and DR4 have been recognized as independent risk factors for autoimmune hepatitis. We compared the clinical features and prognosis of patients with HLA DR4 to those with HLA DR3 and other phenotypes to determine if subclassification by HLA is a valid consideration., Methods: Forty-four patients with HLA DR4; 41 patients with HLA DR3; and 16 patients with neither allele were studied. Ninety patients were treated with corticosteroids., Results: Patients with HLA DR4 were older (51 +/- 2 years vs. 38 +/- 3 years, P = 0.0001) and more commonly women (89% vs. 68%, P = 0.04) than counterparts with HLA DR3. Additionally, these patients had higher serum immunoglobulin G levels (3300 +/- 216 mg/dL vs. 2732 +/- 192 mg/dL, P = 0.05) and a greater frequency of concurrent immunologic diseases (59% vs. 27%, P = 0.005). Similar differences in clinical presentation distinguished the patients with HLA DR4 from those with other phenotypes. Remission during corticosteroid therapy (85% vs. 63%, P = 0.05) occurred more commonly in the patients with HLA DR4 than in those with HLA DR3 and treatment failure (10% vs. 32%, P = 0.03) occurred less frequently., Conclusions: Patients with HLA DR4 have a different clinical profile than counterparts with other phenotypes, and they have a better response to corticosteroid therapy than patients with HLA DR3. Subclassification of patients by HLA DR phenotype may have clinical and prognostic value.

To assess the frequency and genetic predispositions of concurrent immunological diseases and immunoserological markers in autoimmune hepatitis and chronic viral hepatitis, we assessed 185 patients prospectively, including 122 patients with autoimmune hepatitis and 63 patients with viral disease. Human leukocyte antigens were determined in all patients. Sixty patients (32%) had concurrent immunological diseases, and the majority of the diseases (68%) had known human leukocyte antigen associations. Although patients with autoimmune hepatitis had concurrent immunological diseases more commonly than those with viral disease (38% vs. 22%; p = 0.04), the nature of the diseases was similar in both groups, as were the frequencies of human leukocyte antigen-DR4 (42% vs. 39%; p = 0.7). The presence of human leukocyte antigen-DR4 was associated with the concurrence of immunological diseases in both autoimmune (62% vs. 33%; p = 0.01) and viral hepatitis (75% vs. 29%; p = 0.009). In autoimmune hepatitis, human leukocyte antigen-DR4 was also associated with the expression of smooth muscle antibodies and high-titer antinuclear antibodies. We conclude that concurrent immunological diseases and immunoserological markers are common in autoimmune and chronic viral hepatitis. Both conditions have a common genetic predisposition for concurrent immunological disease associated with human leukocyte antigen-DR4. The expression of smooth muscle antibodies and high-titer antinuclear antibodies is associated with human leukocyte antigen-DR4 in autoimmune hepatitis only, suggesting that this response is associated with triggering antigens and immune recognition systems that are different from those in viral disease.

Objective: This study evaluated the outcome of liver grafts from ABO incompatible donors, focusing on biliary complications, and compared the results to an ABO compatible control group. Also, the expression of donor ABH antigens in the liver graft was analyzed., Summary Background Data: The outcome of liver transplantation using an ABO incompatible graft is still debated. These blood group related (ABH) antigens are known to be expressed not only on the surface of the erythrocytes, but also on the epithelial cells of large bile ducts. Because the biliary epithelium of hepatic allografts may continue to express donor ABH antigens, it may be more susceptible to immunologic bile duct injury after transplantation across the ABO barrier., Methods: Eighteen ABO incompatible grafts were compared with 18 ABO compatible grafts in patients who were matched according to medical urgency, primary liver disease (PLD), and recipient age. After transplantation, the grafts were analyzed with cholangiography, Doppler ultrasound, or arteriography and liver histology according to protocol. Immunoperoxidase staining for ABH antigens was performed on hepatic tissue., Results: Biliary complications developed in 82% of the ABO incompatible donors, compared to 6% of the ABO matched controls. Hepatic artery thrombosis occurred in 24%. Cellular rejection was diagnosed in 65% versus only 28% in the control group. The 1-year actuarial graft survival rate was 44% versus 78% in the control group. ABH antigens of the donor were expressed on vascular endothelium and bile duct epithelial cells as long as 150 days after transplant., Conclusions: Using ABO incompatible allografts, a high incidence of biliary and hepatic artery complications and decreased graft survival in liver transplantation were found. An immunologic injury to the bile duct epithelium and/or to vascular endothelium is suspected.

To determine if the hepatitis viruses are important etiologic factors in autoimmune hepatitis, the clinical, immunoserologic, virologic and HLA phenotypes of 105 of the latter patients were assessed prospectively and compared to 45 patients with chronic viral hepatitis. Patients with autoimmune hepatitis were more often women with higher serum aspartate aminotransferase and immunoglobulin levels than patients with viral disease. Only eight patients (8%) were seropositive for anti-HBc and anti-HBs (four patients) or anti-HCV (four patients) and none with anti-HCV were reactive by second generation immunoassay or recombinant immunoblot assay. Smooth muscle (90 vs. 22%, P < 0.001) and antinuclear (70 vs. 22%, P < 0.001) antibodies were more common in patients with autoimmune hepatitis and the titers more frequently exceeded 1:80 (84 vs. 11%, P < 0.0001). Patients with autoimmune hepatitis were more often positive for HLA B8 (48 vs. 20%, P < 0.01) and DR3 (49 vs. 20%, P < 0.003) and they more frequently had the HLA A1-B8-DR3 phenotype (38 vs. 10%, P < 0.003). Only one of the 120 patients tested for anti-LKM1 was seropositive. We conclude that in an American referral population autoimmune hepatitis usually lacks virologic markers and has a distinctive clinical, immunoserologic and HLA phenotype. Hepatitis viruses are not important immunogenic stimuli for non-organ specific antibodies and they are unlikely to be important causes of this form of autoimmune hepatitis.

Background: Cryptogenic chronic active hepatitis may be an autoimmune or viral disease. Our aims were to determine the clinical features, human leukocyte antigen phenotype, and response to corticosteroid therapy of severe cryptogenic chronic active hepatitis and to compare it with these other diseases., Methods: Twelve patients with cryptogenic hepatitis were compared with 94 patients with autoimmune hepatitis and 30 patients with chronic viral hepatitis., Results: Patients with cryptogenic hepatitis were indistinguishable from those with autoimmune hepatitis by age, gender, and individual laboratory and histological findings. HLA B8 (75% vs. 49%, P = 0.2), DR3 (71% vs. 51%, P = 0.5), and A1-B8-DR3 (57% vs. 38%, P = 0.6) occurred as commonly in each group. Patients with cryptogenic hepatitis entered remission (83% vs. 78%, P > 0.9) and failed treatment (9% vs. 11%, P > 0.8) as frequently as those with autoimmune hepatitis during corticosteroid therapy. In contrast, patients with chronic viral hepatitis had lower biochemical abnormalities, less frequent multilobular necrosis at presentation, and different human leukocyte phenotypes than those with cryptogenic or autoimmune disease., Conclusions: Severe cryptogenic hepatitis has a clinical expression, genetic phenotype, and corticosteroid responsiveness that is similar to autoimmune hepatitis. It may be an autoimmune disorder that has escaped detection by conventional immunoserological markers.

Nonanastomotic biliary strictures that involve only the biliary tree of the graft occur after orthotopic liver transplantation in patients with hepatic artery thrombosis, chronic ductopenic rejection and ABO blood group incompatibility. This complication may also occur in the absence of these known risk factors. The major focus of our study was to evaluate the risk factors for nonanastomotic biliary stricturing of unknown cause after orthotopic liver transplantation. Results demonstrate that the development of biliary strictures is strongly associated with the duration of cold ischemic storage of allografts in both Euro-Collins solution and University of Wisconsin solution. Results also demonstrate that strictures are not associated with the type of biliary reconstruction, the primary liver disease, cytomegalovirus infection, allograft rejection or the presence of a positive lymphocytotoxic crossmatch. More recently, we have markedly reduced the occurrence of nonanastomotic biliary stricturing by decreasing the ischemia time of our allografts. Thus nonanastomotic biliary strictures appear to be the result of the ischemia/reperfusion-induced tissue injury associated with the harvest and implantation of allografts.

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection. A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Time-dependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance. In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome.

We implemented a pilot program at our institution for automatic referral of patients for presurgical assessment for preoperative and intraoperative collection of autologous blood. Although patients and clinicians support the use of autologous transfusion, often a request for collection of autologous blood is not initiated. During 11 months, 269 patients (82%) of three orthopedic surgeons entered the program, and 218 underwent operation and were dismissed from the hospital. A total of 940 units of autologous blood (675 preoperatively and 265 intraoperatively) was collected from these 218 patients, and 84% of the units were transfused. Throughout hospitalization, 86% of the patients received only autologous blood, whereas 14% received various proportions of homologous and autologous blood. In contrast, only 26% of a concomitant control group of 220 consecutive orthopedic surgical patients not participating in the automatic-referral program received only autologous blood. Thus, the automatic-referral program increased the percentage of elective orthopedic surgical patients who received only autologous blood from 26% to 86% (P less than 0.001). This study also showed that the same amount of blood was used for autologous transfusions as was routinely used for homologous transfusions in similar cases. The automatic-referral system was convenient for physicians and patients and offered the benefits of reduction of transfusion-associated risks and amelioration of patient anxieties.

Between April 1982 and July 1990, 101 patients underwent allogeneic or syngeneic bone marrow transplantation at the Mayo Clinic. This patient population consisted of 30 with acute nonlymphocytic leukemia, 25 with acute lymphoblastic leukemia, 29 with chronic granulocytic leukemia, and 17 with other diseases (aplastic anemia in 7, myelodysplastic syndrome in 5, and lymphoma in 5). The results achieved in our patients who underwent transplantation in first complete remission of both acute nonlymphocytic leukemia and acute lymphoblastic leukemia compare favorably with previously reported results. Only 1 of 15 patients (7%) with acute nonlymphocytic leukemia and 2 of 8 patients (25%) with acute lymphoblastic leukemia who underwent transplantation in first complete remission had a relapse. Thus, we recommend early bone marrow transplantation during initial complete remission for patients with either of these disorders who have adverse prognostic factors. In contrast, of 12 patients with either acute nonlymphocytic leukemia or acute lymphoblastic leukemia who underwent transplantation during relapse, 11 died within 6 months. Therefore, such patients should be offered new experimental treatments. Our patients with chronic granulocytic leukemia fared better when they underwent transplantation early during the course of their disease rather than during the accelerated or blast phase. Prospective studies are needed to determine the best approach in these patients.

To assess the clinical and prognostic implications of human leukocyte antigen B8 in corticosteroid-treated severe autoimmune chronic active hepatitis, 81 consecutive patients were tested for histocompatibility antigens on the A and B loci, treated with corticosteroids, and followed prospectively for 111 +/- 8 mo. The 47 patients with HLA-B8 were younger (38 +/- 2 yr vs. 48 +/- 2 yr; p less than 0.01), had higher serum levels of aspartate aminotransferase (658 +/- 60 U/L vs. 465 +/- 49 U/L; p = 0.02) and bilirubin (7 +/- 1 mg/dl vs. 2.8 +/- 0.4 mg/dl; p = 0.003), and more commonly had histologic features of bridging necrosis, multilobular necrosis, and cirrhosis (85% vs. 56%; p less than 0.01) at presentation than the 34 patients without HLA-B8. Remission (79% vs. 71%), relapse after drug withdrawal (76% vs. 71%), treatment failure (13% vs. 6%), progression to cirrhosis (46% vs. 32%), and death from liver failure (6% vs. 3%) occurred as frequently in patients with and without HLA-B8. Importantly, HLA-B8-negative patients with HLA-A1 relapsed less frequently than HLA-B8-positive patients with and without HLA-A1- and HLA-B8-negative counterparts without HLA-A1. It is concluded that HLA-B8-positive patients are younger and have more severe disease at presentation than HLA-B8-negative patients. The HLA-B8 phenotype does not influence the response to corticosteroid therapy. HLA-B8-negative patients with HLA-A1 relapse less frequently than other phenotypes.

A case of PlA1-associated posttransfusion purpura (PTP) is reported, in which a previously sensitized patient developed life-threatening thrombocytopenia, purpura, hematuria, and bronchial bleeding. The patient was transfused with PlA1-negative single-donor apheresis platelets (from four different donors) on four occasions. The first transfusion resulted in a 1-hour posttransfusion increment of 57 x 10(9) per L. The use of two additional PlA1-negative apheresis platelets provided support for a tracheostomy. Bronchial bleeding leading to respiratory arrest was controlled with a fourth transfusion. All PlA1-negative platelet transfusions resulted in transient increases in the patient's platelet count. This is the first reported case of repeated, transiently effective transfusion of PlA1-negative platelets demonstrated during the acute phase of thrombocytopenia.

A biopsy study of 60 allografts from 53 patients after orthotopic liver transplantation (OLT) revealed prominent centrilobular necrosis (CN) in 18% of the grafts that were suitable for analysis. The lesions often had a "punched-out" appearance, sometimes with unusual features such as giant cell formation. Persistent CN developed 4 weeks to 6 months after OLT, and persisted in two cases for 2 years and longer. In some instances, CN disappeared or healed by scarring. We found no association between CN and rejection arteritis or arteriopathy. Ductopenic (chronic) rejection subsequently occurred in six of eight livers with CN. Overall, patients with persistent CN had a worse prognosis than control patients. A comparison of cases with matched controls failed to reveal significant differences with respect to perioperative factors such as ischemia time, immunologic test results such as lymphocyte crossmatches, drug administration--in particular, of azathioprine, frequency of cellular (acute) rejection or infection episodes, or frequency of complications affecting major hepatic vessels or bile ducts. Morphologic evidence suggests that in some instances, rejection-induced endotheliitis/phlebitis of hepatic vein branches may lead to sinusoidal outflow blockage, sinusoidal dilatation, and dropout of hepatic cell plates. Although potentially reversible conditions such as ischemia or adverse drug reactions are among the possible causes of CN, severe rejection leading to ductopenia appears to be the most important underlying condition. Thus, presence of CN in repeated biopsy specimens from allografts should be considered a warning sign of irreversible rejection.

HLA-DR locus antigens were determined in 69 patients with giant cell arteritis, polymyalgia rheumatica, or both. The frequencies of HLA-DR4 and HLA-DRW6 in these patients were increased above normals. But the differences were not significant in the total group nor when the patients were separated according to the presence or absence of polymyalgia rheumatica.

Utilizing the diallelic BW4-BW6 system of antigens and antibodies, we divided subjects possessing HLA-BW35 into two groups, depending on the association of their BW35 antigens with BW4 or BW6, and demonstrated in family studies that the associated antigens appeared to be inherited together. Absorption experiments were performed to establish the validity of the typings. Anti-human beta2-microglobulin was used in an effort to "map" the location of the BW4 and BW6 antigenic determinants on the HLA molecule.