Treatment of autoimmune hemolytic anemias.

Treatment of autoimmune hemolytic anemias varies depending on whether the patient has autoimmune hemolytic anemia of warm antibody type, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, or autoimmune hemolytic anemia secondary to an underlying disorder. Initial therapy for warm antibody autoimmune hemolytic anemia should be corticosteroids, such as prednisone at conventional doses of 1 to 1.5 mg/kg/d orally. Criteria must be established to determine whether the therapeutic response is adequate, because long-term therapy may lead to significant detrimental side effects. Splenectomy has the advantage over therapeutic options in that it has the potential for complete and long-term remission. The major adverse effect is the syndrome of overwhelming postsplenectomy infection. Other therapeutic options, which are less likely to have long-term benefit, are immunosuppressive drugs, danazol, intravenous immunoglobulin, and plasma exchange. Therapy of cold agglutinin syndrome often is unsatisfactory. All patients should avoid exposure to cold, and if additional therapy is necessary, the therapies used for warm antibody autoimmune hemolytic anemia may be tried with less likelihood of response. Paroxysmal cold hemoglobinuria requires aggressive supportive therapy, generally supplemented by corticosteroids. Hemolysis usually terminates spontaneously. Patients with secondary autoimmune hemolytic anemia may be treated similarly to those with idiopathic autoimmune hemolytic anemia, and additional therapy for the underlying disorder also may result in remission of the hemolysis.

In vitro studies of the impact of transfusion on the detection of alloantibodies after autoadsorption.

BACKGROUND: In a patient with warm autoantibodies who has recently received a transfusion, it is not recommended to perform adsorptions using autologous RBCs to detect alloantibodies. Although not scientifically documented, this position is based on the theory that transfused RBCs in the patient's circulation would be capable of adsorbing alloantibodies that may be present. This in vitro study was designed to determine what percentage of transfused RBCs might completely remove alloantibodies in vivo. STUDY DESIGN AND METHODS: Selected D, E, K, Fy(a), and Jk(a) antibodies were adsorbed with mixtures of antigen-positive and antigen-negative RBCs to determine the lowest concentration of antigen-positive RBCs capable of removing all alloantibody reactivity. The percentage of antigen-positive RBCs in each mixture was determined by flow cytometry. RESULTS: Small amounts of antigen-positive RBCs (2-6%, as determined by flow cytometry) completely removed anti-D, -E, and -Fy(a) reactivity. Reactivity of two examples of anti-K was removed by 11 percent and 17 percent of K+ RBCs, respectively. Anti-Jk(a) reactivity was completely removed by 4 to 5 percent Jk(a+) RBCs using a PEG adsorption; the endpoint (>11%) was estimated, but complete adsorption with ZZAP-treated RBCs was not performed. CONCLUSION: Small amounts of antigen-positive RBCs are generally capable of removing all alloantibody reactivity. Thus, waiting for 3 months after transfusion before performing autologous adsorptions is a prudent policy.

Selecting donors of platelets for refractory patients on the basis of HLA antibody specificity.

BACKGROUND: Patients who are refractory to platelet transfusion as a result of HLA alloimmunization are generally given HLA-matched or crossmatched platelets. However, HLA-matched platelets that are matched at HLA-A and -B loci (A-matched) or those without any mismatched or cross-reactive antigens (BU-matched) are frequently unavailable. A disadvantage of crossmatching is that crossmatched platelets have a shelf life of only 5 days, so that crossmatch tests must be performed frequently for patients requiring long-term platelet transfusions. An alternative method is the selection of platelets according to the patient's HLA antibody specificity, called the antibody specificity prediction (ASP) method. STUDY DESIGN AND METHODS: An anti-human globulin-enhanced microlymphocytotoxicity test modified by a double addition of serum and a computer program were used to determine the specificity of patients' HLA antibodies. Platelet crossmatching was performed with a solid-phase adherence assay. The percentage of platelet recovery (PPR) was determined in 1621 platelet transfusions in an observational study in 114 patients, and the PPR of platelets selected by the ASP method was compared with the PPR of those that were HLA-matched, crossmatched, or randomly selected. The numbers of potential donors in files of HLA-typed donors as identified by HLA matching vs. the ASP method were determined. RESULTS: After adjustments for covariates, the mean +/- SEM PPR was similar for HLA-matched (21 +/-4%), cross-matched (23+/-4%), and ASP-selected (24+/-3%) platelets and was significantly lower for randomly selected (15+/-1.4%) platelets. For 29 alloimmunized HLA-typed patients, the mean number of potential donors found in a file of 7247 HLA-typed donors was 6 who were an HLA-A match (median = 1), 33 who were an HLA-BU match (median = 20), and 1426 who were identified by the ASP method (median = 1365). CONCLUSION: The ASP method of donor selection for refractory alloimmunized patients appears as effective as HLA matching or crossmatching. Far more donors are identified in a file of HLA-typed donors by the ASP method than by HLA matching, and this indicates that the ASP method provides important advantages regarding the availability of compatible platelet components.

The sickle cell hemolytic transfusion reaction syndrome.

BACKGROUND: Patients with sickle cell anemia may develop serious, life-threatening hemolytic transfusion reactions (HTRs). More severe anemia may develop after the HTR than was present before transfusion, which suggests the possibility of an increased rate of hemolysis of autologous red cells. STUDY DESIGN AND METHODS: The signs and symptoms occurring during eight severe HTRs that occurred in five patients with sickle cell anemia were reviewed, as were published reports by other investigators. Calculations of red cell production and destruction incorporating known correction factors for reticulocyte maturation were performed to determine the most probable mechanism for the striking drop in hematocrit observed in several instances. RESULTS: A characteristic constellation of findings was recognized in some severe HTRs in patients with sickle cell anemia. Calculations of daily red cell production and senescence indicated that a marked drop in hematocrit occurs when erythropoiesis is suppressed in a patient with a short red cell life span and that this could account for severe posttransfusion anemia when donor red cells are hemolyzed during an HTR. CONCLUSION: A sickle cell HTR syndrome was defined. A rapid increase in the severity of anemia occurs in patients with sickle cell anemia when all donor red cells are hemolyzed during an HTR and when there is suppression of erythropoiesis, as commonly occurs as a result of transfusion or concomitant illness. Although an increased rate of hemolysis of autologous red cells may also occur, more definitive data are required to document that in these patients.

A comprehensive transfusion medicine curriculum for medical students. Transfusion Medicine Academic Award Group.

BACKGROUND: The Transfusion Medicine Academic Awards (TMAA) program, sponsored by the National Heart, Lung, and Blood Institute, has provided grants to medical schools to help them develop comprehensive curricula in transfusion medicine. In 1989, the TMAA Group published a set of comprehensive curricular goals for teaching transfusion medicine. The medical student portion of this curriculum has now been revised to reflect new developments in transfusion medicine and recent trends in medical school education. STUDY DESIGN AND METHODS: Two medical schools independently revised the 1989 curriculum for their students. Because significant similarities were noted between curricula of the two institutions, the two revisions were combined and submitted to all TMAA institutions for comment. As a result, a revised medical school curriculum was developed and approved by the TMAA Group. RESULTS: The revised curriculum consists of 28 objectives in six major areas of transfusion medicine. It is presented in its entirety in this article. CONCLUSION: The TMAA transfusion medicine curriculum should provide to medical schools a valuable resource for evaluating their teaching of transfusion medicine and should provide to medical school deans and curriculum committees an authoritative source of transfusion medicine expertise.

Factors affecting the labor efficiency of hospital-based blood bank laboratories.

BACKGROUND: A variety of financing mechanisms and managerial innovations have been developed in the past decade to control hospital costs. Some evidence suggests that those changes have not produced substantial improvements in labor efficiency among employees in the hospital's technical level, such as in the blood bank laboratories. STUDY DESIGN AND METHODS: This study measured labor efficiency in 40 hospital-based blood bank laboratories in Southern California during the year from July 1989 to June 1990 and explored the impact of financial, managerial, and operational factors on labor efficiency. RESULTS: With standardized output measures used in all blood bank laboratories, a wide variation of labor efficiency was found. Multivariate analyses indicate that the labor efficiency of blood bank employees was not influenced by organizational financial incentives, but was affected by the managerial styles of blood bank managers. CONCLUSION: Interpretation of the findings suggests that labor efficiency is affected by operational designs intended to improve responses to variable workloads and reduce slack time.

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors.

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion-associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one-way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA-GVHD.

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.

Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate.

Hemolysis most commonly occurs following bone marrow transplant when there is "minor" ABO blood group incompatibility between donor and recipient. The hemolysis has been attributed to destruction of the patient's incompatible erythrocytes by donor-derived anti-A and/or anti-B antibody produced from "passenger" immunocompetent donor lymphocytes. Extraordinary transfusion requirements of group O erythrocytes in a series of patients receiving unrelated minor ABO-incompatible marrow grafts led us to investigate whether this mechanism could account for the extent of hemolysis observed. In seven consecutive minor ABO-incompatible unrelated-donor bone marrow transplant recipients receiving cyclosporine without posttransplant methotrexate, we observed excessive hemolysis. For cases in this index group, a strongly reactive donor-derived ABO blood group antibody was identified coincident with development of hemolysis. Transfusion requirements in the first three patients (26 U of group O erythrocytes each) greatly exceeded the recipient's volume of incompatible erythrocytes, indicating that lysis of transfused group O erythrocytes was also occurring. Pretransplant erythrocyte exchange transfusion with group O erythrocytes performed in the four subsequent patients decreased the severity of hemolysis, but did not prevent it. Among minor ABO-incompatible marrow graft recipients, an analysis of variance demonstrated effects on transfusion requirements due to donor-recipient relationship being unrelated (P less than .002) and the use of posttransplant methotrexate (P = .0001), and there was interaction between these two factors (P less than .001). Bone marrow transplants from unrelated donors resulted in an exaggerated immune response to ABO blood group antigens, which was associated with hemolysis of transfused group O erythrocytes, as well as the patient's ABO-incompatible erythrocytes. This serious complication may be prevented by posttransplant immunosuppression with methotrexate.