Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41-year- old man with chronic myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA-identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous-flow blood cell separator. The patient was given group O Rh-positive RBCs and group A Rh-positive platelets. Prophylaxis for graft-versus-host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti-M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti-K. During the second hemolytic episode (Day 35), the patient's blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the serum. Eluates made from the recipient's RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum and in an eluate made from the patient's RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.     

Blood transfusion costs: a multicenter study

The cost of delivering a unit of blood (whole blood or red cells) to a hospitalized patient was examined in 19 United States teaching hospitals. The average hospital acquisition cost was calculated by using the prices charged by regional blood centers for blood products. To this cost was added an estimate of costs incurred by hospitals for handling, testing, and administering blood. Across study sites, the average hospital cost per unit transfused was $155 and the average charge to the patient was $219. Acquisition cost, the price that hospitals pay for blood, was 37 percent of the total cost to the hospital; the other 63 percent of the hospital cost included costs for blood bank handling (13%), laboratory tests (43%), and blood administration (7%). Significant variations in blood transfusion cost were found within our sample. Most of the variability can be attributed to geographic location of the blood supply source, type of red cell product transfused, prices charged by blood transfusion services, and the frequency of laboratory tests. The results of this transfusion cost study may be helpful in determining the costs of health care delivery, especially when blood transfusions are indicated.     

Interleukin-4 stimulates human monocytes to produce tissue-type plasminogen activator

Tissue-type plasminogen activator (t-PA) is involved in the lysis of blood clots (fibrinolysis) and is used clinically for this purpose. Endothelial cells are one source of the t-PA present in blood. We report here that interleukin-4 (IL-4) (0.1 to 0.25 U/mL; 1 to 3 x 10(- 11) mol/L), but not interferon-gamma (IFN-gamma), elevates t-PA messenger (m)RNA expression and secretion of t-PA activity by human monocytes, with the maximum response at 2.5 U/mL. Supernatant t-PA activity was detected within three hours of exposure to IL-4 and maximum activity within six hours. Thus, IL-4 may control fibrin deposition at sites of inflammation during cell-mediated immune responses, as well as having a therapeutic role in thrombolysis.     

Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity

Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known. Methods: for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.     

Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma

Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.     

The genetic basis of immune and autoimmune responses

HLA class I and class II molecules play a major role in the presentation of short, pathogen-derived peptides to T cells, a process that initiates the adaptive cellular and humoral immune responses. However, the factors governing a cell's ability to respond or not to particular peptides are still not completely understood. Taking the example of a viral infection, in tissues infected with a virus, viral particles are taken up by antigen-presenting cells and uncoated. The viral DNA or RNA enters the nucleus, where it replicates. mRNA enters the cytosol and is transcribed into proteins. These proteins are degraded in proteasomes and the resulting peptides (8–10 residues) are loaded onto class I molecules for export to the surface of the cells. In the meantime, the groove of the class II molecules is also preparing to accommodate peptides (12–24 residues) generated by the endocytic protein-processing pathway. The surface of the infected cell then becomes adorned with peptide-loaded human leukocyte antigen (HLA) molecules. CD4⁺ T helper lymphocytes engage class II molecules and elicit responses from B cells, which will ultimately lead to antibody production, whereas CD8⁺ T lymphocytes become cytotoxic T cells. As a consequence, the virus is eliminated from the body. However, certain mysteries and challenges remain. How can, as an exception to this rule, an autoimmune response be the escape from the perfect machinery? This review offers some hypotheses on how to see the problem through to its solution.