S. Breanndan Moore

Roles of the Neutrophil and Other Mediators in Adult Respiratory Distress Syndrome

The adult respiratory distress syndrome (ARDS) and transfusion-related acute lung injury (TRALI) are characterized by diffuse, acute lung injury. Most likely, TRALI is a type of ARDS although it is associated with a much lower morbidity and mortality than found with classic ARDS. For years, the pathogenesis of ARDS has been explained by the complement hypothesis in which pulmonary neutrophilic sequestration and degranulation follow complement-mediated neutrophil chemotaxis. A definitive role for the neutrophil in diffuse, acute lung injury, however, has not been established. Although numerous chemoattractants for neutrophils are generated in the lungs and, through degranulation and formation of toxic oxygen free radicals, the neutrophil is fully capable of causing tissue injury, substantial evidence refutes the requirement for neutrophils in diffuse, acute lung injury. Other potential factors in the pathogenesis of ARDS include primary endothelial cell injury, alveolar macrophage activity, and hemostatic disorders.

Immunologic Mechanisms in the Maternal-Fetal Relationship

Until recently, the immunologic tolerance between a mother and her allogeneic fetus has been a highly speculative and poorly understood phenomenon. New data indicate that maternal acceptance of the fetal allograft necessitates a specific, protective immune response. This specific recognition apparently involves unique placental antigens with genes that are closely linked to HLA loci. Lack of recognition of these antigens, as in matings between partners with similar HLA profiles, may result in repeated spontaneous abortions caused by unsuppressed rejection mechanisms.

Evidence for Linkage of IgA Deficiency With the Major Histocompatibility Complex

A 57-year-old woman with IgA deficiency and Stills disease was the proband in a 20-member, three-generation kindred in which we studied the possible linkage of IgA deficiency with her HLA-A1-B8 haplotype. The presence of paternal A1-B8 haplotype complicated the analysis. Known maternal HLA-A1-B8 haplotype, present in three of the children of the proband, was associated with IgA deficiency, whereas all five family members with exclusively paternal A1-B8 had normal IgA. Of three third-generation family members whose A1-B8 haplotype was of indeterminate origin--that is, potentially either maternally or paternally derived--two had IgA deficiency and one did not.

Transfusion-induced alloimmunization in patients awaiting renal allografts

Abstract. Lymphocytotoxic antibodies can be induced by the immunologic stimulus of pregnancy, blood transfusion, or tissue allograft. The presence of such antibodies can delay or prevent renal transplantation. However, a history of prior transfusion exposure has been strongly associated with excellent renal allograft survival. The problem of ensuring this ‘transfusion effect’ while minimizing the risk of alloimmunization is real for patients awaiting renal allografts. We examined the influence of pregnancy, allograft rejection, and transfusions on the levels of lymphocytotoxic antibodies in the sera of patients awaiting renal transplantation. The results indicate that transfusions alone have a minimal effect on alloimmunization in men and in nulliparous women. The influence of transfusions alone was seen with 77% of men and 86% of women showing less than 10% panel reactivity. Deliberate transfusion policies for patients awaiting renal allografts should be designed to minimize transfusion exposure to parous patients or those who have previously rejected a renal graft.

A blood bank consultation service: principles and practice

In the blood bank setting, a close relationship with both clinicians and patients is essential for good medical practice. In July 1982, the Mayo Clinic Blood Bank and Transfusion Services formally organized a consultation service with daily visits to patients of mutual interest to blood bank consultants and clinicians for practice and education. Detailed diaries of this activity were maintained for 12 months, during which time 802 impatient visits were recorded. The most frequent reasons for consultations were clarification or amplification of the clinical history (34.0%), evaluation of transfusion reactions (27.2%), and assessment of serologic problems (18.2%). These consultations resulted in diagnostic, management, and therapeutic recommendations for a wide variety of medical problems. Of the 802 consultations, 23% were conducted at the direct request of clinicians. We believe that a blood bank consultation service is feasible, is enlightening for the blood bank and clinicians, and contributes to patient care.

Morning Admission for a Same-Day Surgical Procedure: Resolution of a Blood Bank Problem

To minimize the risks associated with an elective surgical procedure on the day of admission without adequate time for blood bank serologic analysis, we implemented two administrative changes: (1) collection of blood samples from patients on the evening before operation and (2) a system for recommending a 3-hour delay of the operation in those cases without such a sample. During a 4-month period before implementation of these changes, 70 patients had serologic problems; morning blood samples had been obtained from 36 of these patients. For a comparable time after implementation of these changes, a serologic problem was encountered in 41 surgical cases, in 7 of which morning blood samples had been obtained. Similarly, the number of cases in which the operation was begun before resolution of a serologic problem decreased from 19 to 3. These decreases occurred despite a 13.4% increase in total morning-admission cases between the first and second study periods. Although no patient experienced adverse transfusion-related events during either study period, simple administrative changes that necessitated no increases in costs were instrumental in substantially decreasing the risks to patients.

The Role of the Lewis Antigen System in Renal Transplantation and Allograft Rejection

The recent literature on the technologic and clinical progress being made in renal transplantation has not emphasized applicable advances in blood group serology. Accumulated data on the Lewis blood group system, however, seem to implicate Lewis incompatibilities between kidney donors and recipients as contributing factors in allograft rejection. Lewis antigens may be capable of inciting both cell-mediated and humoral immune responses of a cytotoxic nature, and such antigens are expressed on cell surfaces of the renal parenchyma in Lewis-positive persons. Hence, this serologically defined system could be the source of diminished allograft survival in recipients who are mismatched with their organ donors for Lewis antigens, despite compatibility within other histocompatibility antigen systems. This premise is still open to question, and future, controlled, clinical studies will be necessary to establish a definite role for the Lewis antigen system in renal transplant rejection.

A Study of HLA Antigens in Alcoholism

The concept that alcoholism may be inherited has been suggested on the basis of twin and adoption studies and the further evidence that alcoholism is commonly seen in several members of a family. Genetic marker studies that have been conducted among alcoholics have often yielded seemingly contradictory results. Thus far, genetic marker studies involving HLA antigens have not been used in the study of alcoholism. In the current study, we identified and performed HLA typing in 52 alcoholics to determine whether a significant difference existed between the frequency of HLA-A and HLA-B locus antigens in an alcoholic population and that in a control population consisting of 1,704 nonalcoholic blood donors. In this study, we could not demonstrate a difference in the occurrence of these antigens between the two populations.

Platelet Crossmatch Evaluation in Refractory Hematologic Patients

Although previous investigators have attempted to identify platelet crossmatching methods that could be used routinely for pretransfusion testing, such studies have excluded patients with underlying clinical conditions inherently associated with low corrected platelet increments. Because many refractory hematologic patients have such underlying conditions, we decided to assess the usefulness of platelet crossmatching (in addition to HLA matching) in determining the posttransfusion corrected platelet count increment in eight medically complicated patients who received a total of 35 single-donor platelet transfusions. In this limited study, the predictive value of a negative crossmatch was only 55%, whereas that of a positive crossmatch was 88%. The test used had a sensitivity of 65% and a specificity of 83%. The results of our study suggest that platelet crossmatching may be a useful additional study for predicting the outcome of transfusion--even in medically complex cases--if it can be done rapidly and relatively inexpensively.

Immune Thrombocytopenias: Tests for Platelet Antibodies

In a study of 49 consecutive patients for whom a test for platelet antibodies had been ordered, tests were performed for both cell-bound and serum platelet antibodies. In cases of autoimmune thrombocytopenia (ITP), the test result for cell-bound antibody was more likely to be positive than was the test result for serum antibody. In three patients with ITP who were taking systemic corticosteroids, however, the result of the CBPAT was negative. A similar phenomenon occurred in a patient with SLE. The result of the SPAT correlated best with the presence of alloantibodies formed during pregnancy or after blood transfusion.