Irma O. Szymanski

A multicenter study of in vitro and in vivo values in human RBCs frozen with 40-percent (wt/vol) glycerol and stored after deglycerolization for 15 days at 4°C in AS-3: assessment of RBC processing in the ACP 215

BACKGROUND: The FDA has approved the storage of frozen RBCs at –80°C for 10 years. After deglycerolization, the RBCs can be stored at 4°C for no more than 24 hours, because open systems are currently being used. Five laboratoris have been evaluating an automated, functionally closed system (ACP 215, Haemonetics) for both the glycerolization and deglycerolization processes.

Effect of Recombinant Human Erythropoietin on Transfusion Risk in Coronary Bypass Patients

BACKGROUND Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.

EPSTEIN-BARR VIRUS INFECTIONS IN THE X-LINKED RECESSIVE LYMPHOPROLIFERATIVE SYNDROME

Prospective studies demonstrated variable phenotypic expression of the X-linked recessive lymphoproliferative syndrome (X.L.R.L.S.) in three brothers: (1) hypogammaglobulinaemia and subclinical Epstein-Barr-virus (E.B.V.) infection with antibody response to E.B.V.; (2) E.B.V. infection with defective immune response to E.B.V., fatal infectious mononucleosis (I.M.), and immunoblastic lymphoma; and (3) histiocytic lymphoma. Hypogammaglobulinaemia and measles pneumonitis had preceded infection with E.B.V. The diverse phenotypic expressions probably resulted from the varied immune response to E.B.V. Recombination of X chromosomes was documented by Xg-blood-group studies in a survivor. E.B.V. can induce fatal I.M. and malignant lymphoma in X.L.R.L.S., but an immune response to E.B.V. can be protective.

Increased Apoptosis of CD20+ IgA+ B Cells is the Basis for IgA Deficiency: The Molecular Mechanism for Correction In Vitro by IL-10 and CD40L

IgA deficiency is the most common primary immunodeficiency in humans. Comparative analysis of gene expression in PBMC from IgA-deficient (IgAd) and normal donors using functional multiplex panels showed overexpression of the Caspase-1 (CASP-1) gene. Cells from all the IgAd donors (n=7) expressed 4–10-fold caspase-1 mRNA over normal controls (n=5). CD19+ B cells from all IgAd donors produced IgA in cultures following IL-10 and CD40L with Staphylococcus aureus (Cowan) (SAC) or tetanus toxoid (TT) treatments. In CD19+ B cells from IgAd donors, reconstitution of IgA secretion was associated with protection of the CD20+ B cell population that underwent apoptosis in the absence of IL-10, CD40L, and TT (triple treatment). Caspase-1 gene expression was decreased in the reconstituted cells. Furthermore, treatment with a caspase-1 inhibitor also independently protected against B cell apoptosis in vitro. An apoptosis-specific cDNA array showed differential expression of 4 out of 96 genes and a shift towards survival-related gene expression from the apoptotic to the protected B cells after triple treatment. There was an increase in the expression of the IAP-2 (inhibitor of apoptosis) gene in the reconstituted cells. Upregulation of the IAP-2 gene protects B cells from deletion and allows for IgA secretion in this system. The inability to detect secreted IgA in IgAd patients could result from the loss of IgA-committed B cells that express high levels of caspase-1.

Effect of rejuvenation and frozenstorage on 42-day-old AS-1 RBCs

BACKGROUND: The FDA has approved a 42‐day storage period for RBCs stored in ADSOL (AS‐1). This study was undertaken to provide data for the FDA about the feasibility of salvaging AS‐1 RBCs at the end of their storage period by rejuvenation and freezing.

Evaluation of double 51Cr technique.

Summary. The post‐transfusion survival of multiple units of concentrated red cells was measured by 51chromium automated differential agglutination and double 51chromium technics. Since the mean 24 h survivals were similar with both assay methods, these methods are considered acceptable in evaluating red cell preservation. Analysis of the paired data, however, revealed a significant difference in the results, indicating that an average of 3% of 51chromium eluted from red cells during the first 24 h.

Transfusion‐Associated Graft‐versus‐Host Disease in an Immunocompetent Patient following Cardiac Surgery

Objectives: We determined which of the 22 blood components obtained from unrelated donors and transfused to an apparently immunocompetent patient following open heart surgery caused transfusion–associated graft–versus–host disease (TA–GVHD). Methods: Serologic and molecular methods were used to type the donors, the patients family members, and the patients postmortem tissues for HLA and a genetic marker on chromosome 17. Results: Two donors were homozygous for the HLA class I antigens A1 B8, for which the patient was heterozygous. Both donors were heterozygous, not homozygous as expected, for the class II alleles. One of them had the same class II alleles as the patient (DRB1*0301, DRB3*0101/DRB1*0404, DRB4*0103). The patients tissues were chimeric for restriction fragments at 17p13 of this donor. Conclusion: One–way HLA match leading to TA–GVHD can be caused by donor blood that is homozygous for class I and heterozygous for class II alleles. Two blood components given to our patient had such one–way HLA match. Class II alleles of the lymphocytes in one component were identical with those of the recipient and caused TA–GVHD. Class II alleles of the lymphocytes in the other component differed from those of the recipient and were eliminated either by the immune system of the patient or the lymphocytes that caused the TA–GVHD (graft versus graft).

Motivation of Plateletpheresis Donors

Twenty randomly chosen voluntary plateletpheresis donors were interviewed in depth. Information on their family histories, past histories, present psychosocial adjustment, and history of blood donation was elicited. Most donors had a high level of commitment and drive to achieve, frequently related to low self‐image dating from childhood. The act of platelet donation had several important meanings for the subjects. It improved their self‐esteem, making them feel more worthy and responsible persons. It provided them with an opportunity to establish relationships with others. The data obtained in this survey suggest that the altruistic behavior of the voluntary donors should be seen both as an act of giving and also one of receiving emotional gratification which fulfills ones important psychological needs. Utilization of these data in recruitment of plateletpheresis donors is suggested.

Relationship between the third component of human complement (C3) bound to stored preserved erythrocytes and their viability in vivo.

Abstract. In this study we evaluated whether the 4 °C storage‐induced coating of red blood cells (RBC) with molecules of the third component of human complement, C3, affects the viability of the preserved RBC. To this end, we determined whether the amount of C3 bound to preserved RBC correlated with the 24‐hour survival value. The % anti‐C3c‐induced agglutination of stored RBC provided an estimate of the amount of RBC‐bound C3. In some cases, the number of RBC‐bound C3c‐containing molecules was also quantitated. The 24‐hour survival of autologous RBC was measured in 114 cases. All units were initially stored at 4°C as RBC concentrates followed in 21 cases by frozen storage and in 75 cases by biochemical rejuvenation and frozen storage.

Sterility of single‐donor apheresis platelets

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