bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Canadian Hemophilia Registry as the basis for a national system for monitoring the use of factor concentrates
Authors: Walker I. R. , Pai M. K. , Akabutu J. J. , Ritchie D. Bruce , Growe G. H. , Poon M.‐C. , Card R. T. , Ali S. Kaiser , Israels S. , Teitel J. M. , Garvey B. , Blanchette V. , Giles A. , Lillicrap D. , Drouin J. , Luke B. , Gill K. , Herst J. , Lépine‐Martin M. , Inwood M. , Rivard G. , Strawczynski H. , Jobin F. , Demers C. , Jardine L. , Whitman L. , Ingram L. , Robinson S. , Rubin S. , Scully M.‐F. , Dolan S. , Ross E. 
Published: March 2003

BACKGROUND: Canada's publicly funded blood system has recently introduced high‐purity concentrates as the standard treatment for individuals with hemophilia. The added cost and the need to document patient outcomes have prompted the consideration of a national blood product monitoring system.STUDY DESIGN AND METHODS: This study investigates the suitability of the Canadian Hemophilia Registry (CHR) as the basis of such a monitoring system by assessing the degree to which it represents users of factor concentrates.RESULTS: Currently, there are 1978 individuals registered with the CHR, of whom 1594 (81%) have hemophilia A and 384 (19%) have hemophilia B. The total prevalence is 7.2 per 10(5) population, with the prevalence of severe cases being 2.3 per 10(5). This overall prevalence is similar to that seen in other countries with national registries. The CHR national prevalence also compares favorably with that in the province of Quebec, where registration of users of blood products is compulsory. The CHR figures indicate that the number of persons currently infected with human immunodeficiency virus, both alive and dead, is 652, which is similar to the number of applicants (658) to the federal government's assistance program. The registry is stable, and the number of persons with severe cases, other than young children, newly registered or lost to follow‐up during the last 2 years is very small.CONCLUSION: The CHR includes the vast majority of factor concentrate users and is therefore ideal as the basis for a national monitoring system.
Platelet refractoriness and alloimmunization in pediatric oncology and bone marrow transplant patients
Authors: Hogge D.E. , McConnell M. , Jacobson C. , Sutherland H.J. , Benny W.B. , Massing B.G. 
Published: March 2003

BACKGROUND: The purposes of this study were to determine the overall incidence of platelet refractoriness and alloimmunization among multiply transfused children on a medical oncology and bone marrow transplant service and to evaluate the effect of routine white cell reduction in blood components on that incidence.STUDY DESIGN AND METHODS: The platelet transfusion records of 128 consecutive children admitted to the hospital and requiring blood component support for the treatment of disease were evaluated retrospectively. Mean corrected count increments (CCIs) for each patient were calculated for all random‐ donor platelet transfusions given within 7 days of the routine weekly testings of the patient's serum for lymphocytotoxic antibodies (LCTAbs). Mean CCIs for HLA‐matched platelet transfusions were calculated separately for the patients receiving them.RESULTS: Thirty‐ one patients (24%) had or developed persistently positive LCTAbs (patient's serum reacted with > or = 3/10 panel lymphocytes); 22 (71%) of these patients had a mean CCI < 7.5 to random‐donor platelet transfusions. In contrast, of the 97 patients with negative or transiently positive LCTAbs, only 25 (26%) had a mean CCI < 7.5. The overall incidence of platelet refractoriness (CCI < 7.5) was 37 percent. Patients with acute myelogenous leukemia had a significantly (p < 0.01) reduced incidence (17%) of low CCIs, with or without positive LCTAbs, as compared to patients with other malignant or nonmalignant disorders (41%). No difference in the incidence of LCTAbs or low CCIs was seen in patients undergoing allogeneic or autologous bone marrow transplant or receiving drug therapy only. Among the 24 patients who received HLA‐matched platelets, only those with positive LCTAbs showed a significant improvement in CCIs over that achieved with random‐donor platelet transfusions. Routine white cell reduction in red cell and platelet components with third‐generation white cell filters was performed prior to transfusion in 73 of the patients. There was no significant difference between the incidence of LCTAbs and/or low CCIs in this group and that in the 55 children receiving unfiltered transfusions.CONCLUSION: Alloimmunization and platelet refractoriness occur in pediatric oncology and bone marrow transplant patients, but the incidence‐particularly in children with acute myelogenous leukemia‐ ‐appears to be low. The detection of LCTAbs predicts a poor response to random‐donor platelet transfusion, but most such patients show improved CCIs with HLA‐matched platelets. Routine use of white cell‐reduction filters has thus far failed to eliminate alloimmunization in children requiring prolonged blood component support.
Red cell surface cysteine residue (285) of D polypeptide is not essential for D antigenicity
Authors: Suyama K. , Lunn R. , Goldstein J. 
Published: March 2003

BACKGROUND: Only one surface cysteine residue (285) has been thought to be involved in D antigenicity, according to studies using lyophilized or nonlyophilized red cell membranes. However, it has been reported that a 17‐kDa chymotryptic fragment containing the N‐terminus but not this cysteine residue is associated with D antigenicity.STUDY DESIGN AND METHODS: The role of the sulfhydryl (SH) group in D, c, and E antigenicity is assessed by using intact red cells treated with the reagents N‐ethylmaleimide, 5,5′‐dithiobis(2‐nitrobenzoic acid), and 2‐ (4′‐maleimidylanilino)‐ naphthalene‐6‐sulfonic acid. Antigenicity was appraised by hemagglutination titers and immunoprecipitation using human anti‐D, ‐c, and ‐E.RESULTS: Treatment with N‐ethylmaleimide or 5,5′‐dithiobis(2‐nitrobenzoic acid) at various concentrations (< or = 5 mM) or for various times (< or = 120 min) did not cause significant decrease in hemagglutination titers as compared to untreated intact red cells. Moreover, immunoprecipitation of Rh antigen‐carrying peptides by human anti‐D was not affected by prior treatment with N‐ethylmaleimide or 2‐(4′maleimidylanilino)‐naphthalene‐6‐sulfonic acid. Efficacy of blockage of SH groups was demonstrated by inhibition of palmitic acid uptake by the Rh polypeptides for prior treatment with N‐ethylmaleimide and by the presence of fluorescent Rh polypeptides for prior treatment with 2‐(4′maleimidylanilino)‐naphthalene‐6‐sulfonic acid.CONCLUSION: SH group involvement is not essential for D, c, or E antigenic expression in intact red cells.
Prevention of transfusion‐associated Chagas' disease: efficacy of white cell‐reduction filters in removing Trypanosoma cruzi from infected blood
Authors: Moraes‐Souza H. , Bordin J.O. , Bardossy L. , MacPherson D.W. , Blajchman M.A. 
Published: March 2003

BACKGROUND: Transfusion‐associated Chagas' disease (TA‐CD) is a worldwide problem. Measures adopted to prevent TA‐CD include the clinical and serologic screening of blood donors and/or the inactivation of Trypanosoma cruzi present in collected blood, using gentian violet as the trypanocidal agent. This study investigated the efficacy of white cell‐reduction filters in removing T. cruzi from infected blood.STUDY DESIGN AND METHODS: Human blood was contaminated with 2 or 150 T. cruzi parasites per mL and then left unfiltered or filtered with white cell‐reduction filters that provided either 2, 3, or 6 log10 white cell removal. The efficacy of the parasite removal of these filters was evaluated by microscopic enumeration of active forms of T. cruzi both in vivo and in vitro. The in vivo experiments were done in Swiss mice that had been intraperitoneally inoculated with T. cruzi‐infected human blood. The in vitro experiments were performed with fresh human blood that had been deliberately contaminated with T. cruzi.RESULTS: The number of parasites seen in mice inoculated with unfiltered blood containing 2 or 150 parasites per mL was significantly higher than the number of parasites seen in mice inoculated with blood from the same sample, but filtered with white cell‐reduction filters providing 3 or 6 log10 white cell removal. Fifty to 70 percent of the mice given T. cruzi‐infected (2 parasites/mL) filtered blood did not develop T. cruzi infection. In vitro, the use of white cell‐reduction filters, providing 2, 3, or 6 log10 white cell removal, significantly reduced the number of parasites seen in culture.CONCLUSION: The present experimental data provide evidence that white cell‐reduction filters are effective in reducing the number of parasites in T. cruzi‐ infected blood and that this efficacy depends, in part, on the concentration of parasites in the artificially infected blood. Properly designed clinical studies of known carriers of T. cruzi must be conducted to determine whether the use of white cell‐reduction filters may be an alternative method of reducing the incidence of TA‐CD.
In vitro and in vivo persistence of reticulocytes from donor red cells
Authors: Perry E.S. , Moore R.H. , Berger T.A. , Billups L.C. , Maybee D.A. , Salata K.F. , Lippert L.E. 
Published: March 2003

Background: Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit.Study Design and Methods: Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37°C by using thiazole orange staining and flow cytometric analysis. Two‐color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients.Results: Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA‐1 blood was temperature‐dependent. Reticulocytes disappeared over 13 and 6 days at 24°C and 37°C, respectively, but at 4°C the reticulocyte count changed little over 35 days. Two‐color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients.Conclusion: This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.
Anaphylaxis after treatment with recombinant factor VIII
Authors: Shopnick R.I. , Kazemi M. , Brettler D.B. , Buckwalter C. , Yang L. , Bray G. , Gomperts E.D. 
Published: March 2003

Background: Treatment of hemophilia patients with recombinant factor VIII concentrates has not previously been associated with anaphylaxis.Study Design and Methods: A 5‐week‐old boy with severe hemophilia A developed dyspnea, cyanosis, hypotension, and a diffuse urticarial rash following treatment with a recombinant factor VIII (Recombinate). To identify the cause of anaphylaxis in this patient, the vial lot was examined for the presence of endotoxin, and a checkerboard immunoblotting technique was used to test serum and/or plasma samples from the patient and mother for the presence of antibodies (IgA, IgG, IgE, and IgM) to Recombinate‐related antigens (recombinant factor VIII, von Willebrand factor, human serum albumin, Chinese hamster ovary proteins, bovine serum albumin, mouse monoclonal anti‐human factor VIII, polyethylene glycol 3350), and to ethylene oxide, the agent used to sterilize the infusion equipment.Results: No immune response directed against the Recombinate‐related antigens or ethylene oxide that could be associated with the anaphylactic reaction was identified. Endotoxin was not present upon rabbit pyrogen testing of the therapeutic product.Conclusion: These studies failed to show any association between Recombinate and the onset of the allergic reaction. This seems to be the first reported case of anaphylaxis following the infusion of a recombinant form of factor VIII concentrate.
Changes in blood counts after the administration of granulocyte‐colony‐ stimulating factor and the collection of peripheral blood stem cells from healthy donors
Authors: Stroncek D.F. , Clay M. E. , Smith J. , Ilstrup S. , Oldham F. , McCullough J. 
Published: March 2003

BACKGROUND: After the collection of granulocyte‐colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells from healthy donors, the donor platelet counts fall. However, the magnitude and duration of this decrease are not known. STUDY DESIGN AND METHODS: Sixty healthy people were given G‐CSF (5, 7.5, or 10 micrograms/kg/day) for 5 days (Days 1–5), and 1 peripheral blood stem cell component was collected on Day 6. The platelet count, white cell count, absolute neutrophil count, hematocrit, and red cell count were measured before administration of G‐CSF (Day 0), before collection of peripheral blood stem cells on Day 6, and on Days 8, 10, 13, 16, and 20.RESULTS: The platelet count fell from 261 +/− 47 × 10(9) cells per L on Day 0 to 159 +/− 30 × 10(9) cells per L on Day 8 (p < 0.0001) and reached its lowest level on Day 10 (146 +/− 30 × 10(9)/L; p < 0.001). Compared to Day 0 levels, the platelet count was lower on Day 13 (185 +/− 49 × 10(9)/L, p < 0.001), was the same on Day 16 (270 +/− 53 × 10(9)/L), and was greater on Day 20 (333 +/− 60 × 10(9)/L, p < 0.0001). The white cell count returned to pretreatment values on Day 13, and the absolute neutrophil count returned to pretreatment values on Day 10 (Day 0 white cell count = 6.05 +/− 1.59 × 10(9)/L and Day 0 absolute neutrophil count = 3.97 +/− 1.52 × 10(9)/L). On Day 20, both were less than pretreatment values (white cell count = 5.14 +/− 1.24 × 10(9)/L, p = 0.0007 and absolute neutrophil count = 3.20 +/− 1.24 × 10(9)/L, p = 0.0036). The red cell counts on Day 16 (4.52 +/− 0.41 × 10(12)/L) and Day 20 (4.42 +/− 0.39 × 10(12)/L) were less than Day 0 values (4.73 +/− 0.43 × 10(12)/L, p = 0.008 and p < 0.0001, respectively). The hematocrit on Day 20 (39.2 +/− 3.2%) was also less than that on Day 0 (41.2 +/− 4.8%; p = 0.01). The changes in these blood counts were not affected by the dose of the G‐CSF.CONCLUSION: After stimulation with granulocyte‐colony‐stimulating factor and the collection or peripheral blood stem cells, the platelet counts in normal donors were decreased for at least 7 days (Days 6–13). Two weeks after collection of peripheral blood stem cells (Day 20), platelet production was increased, but the production of neutrophils and red cells was decreased. If two or more peripheral blood stem cell components are collected, then the platelet count should be measured after the second and subsequent collections. Further studies on the long‐term effect of G‐CSF on blood counts are needed.
A simple and rapid competitive enzyme‐linked immunosorbent assay to identify HPA‐1a (PlA1)‐negative donor platelet units
Authors: Denomme G. , Horsewood P. , Xu W. , Smith J. , Kelton J. 
Published: March 2003

Background: Alloantibodies to HPA‐1a (PlA1) are the major cause of neonatal alloimmune thrombocytopenia and posttransfusion purpura and have been implicated in refractoriness to random‐donor platelet transfusions. However, most assays used to phenotype platelets are cumbersome or time‐consuming for large numbers of samples. Study Design and Methods: A simple, competitive (inhibition) enzyme‐linked immunosorbent assay for HPA‐1a phenotyping of donor platelets was developed. A segment from the donor platelet unit transfer line was sealed to obtain a small aliquot of platelets. These platelets were washed once and added to a predetermined dilution of serum containing alloantibodies to HPA‐1a. Residual anti‐HPA‐1a binding to the glycoprotein IIb/IIIa purified by lectin and high‐performance liquid chromatography and coated on microtiter wells was detected with a conjugated antihuman IgG. A lack of inhibition equivalent to control (no platelets) was used to determine that the platelets were HPA‐1b/b. Results: Of the 557 platelet units tested, 14 (2.5%) were found to be HPA‐1a negative, and they were confirmed to be HPA‐1b/b by DNA genotyping. Two of the 14 HPA‐1b/b units were also HPA‐3b/b (approx. 0.35% of the random population). Use of the microtiter format allows 100 to 200 samples to be processed per day. Conclusion: This simple and inexpensive assay is useful for identifying HPA‐1b/b units for platelet‐compatible transfusions or for platelet antibody investigations.
Effectiveness of very low doses of subcutaneous recombinant human erythropoietin in facilitating autologous blood donation before orthopedic surgery
Authors: Sans T. , Bofill C. , Joven J. , Clivillé X. , Simó J.M. , Llobet X. , Peró A. , Galbany J. 
Published: March 2003

Background: Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. Study Design and Methods: Fifty‐two patients, scheduled for orthopedic surgery, were enrolled in a double‐blind and placebo‐controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. Results: Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p < 0.01) cumulative increase in red cell volume during the study period (297 ± 127 vs. 121 ± 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p < 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p < 0.05 and p < 0.01, respectively). Conclusion: Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost‐benefit ratio of blood conservation interventions. Doses ≤ 60 IU per kg are ineffective in facilitating such collections in this surgical setting.
Inhibition of cytokine accumulation and bacterial growth during storage of platelet concentrates at 4° C with retention of in vitro functional activity
Authors: Currie L.M. , Harper J.R. , Allan H. , Connor J. 
Published: March 2003

BACKGROUND: The potential for bacterial contamination limits the storage of platelet concentrates (PCs) at 22° C to 5 days. In addition, storage of platelets under conventional protocols for longer times (> 3 days), in the absence of white cell filtration, has been correlated with incidents of cytokine‐associated febrile reaction in recipients. It has been demonstrated that the addition of a reagent mixture of second‐messenger effectors allows platelets stored at 4°C to maintain significant in vitro functional activity. Thus, the effects of 4°C storage on the growth of bacteria and the accumulation of cytokines by the white cell fraction of PCs were analyzed to demonstrate the benefits of this refrigerated storage system.STUDY DESIGN AND METHODS: The platelet storage solution was added directly to PCs obtained from the blood bank, and these treated PCs were stored at 4° C without agitation. In parallel, control PCs were stored according to standard blood‐banking procedures. On Days 1, 3, 5, and 9, the PCs were measured for the plasma concentrations of cytokines. Treated and control PCs stored at 4°C and 22°C were inoculated with low‐titer Staphylococcus aureus, and bacterial growth was measured over a 5‐day period.RESULTS: Control PCs displayed a time‐dependent increase in the plasma concentration of interleukin 6, interleukin 1β, and tumor necrosis factor α. These conventionally stored PCs also displayed a time‐dependent increase in the bacteria titer. In contrast, the treated PCs stored at 4°C displayed no accumulation of the above cytokines in the plasma fraction and no increase in bacteria titer above the initial inoculation.CONCLUSION: The storage of PCs at refrigerated temperatures inhibits the accumulation of white cell‐produced cytokines in the PCs, an effect that could alleviate cytokine‐associated febrile transfusion reactions The 4°C storage was also bacteriostatic, which indicates that the storage of PCs at that temperature increases safety by decreasing the potential for sepsis. Thus, the ability to store PCs at 4°C may allow extension of the storage limit beyond 5 days.
A retrospective analysis of microbial contaminants in outdated random‐donor platelets from multiple sites
Authors: Leiby DA. , Kerr K.L. , Campos J.M. , Dodd R.Y. 
Published: March 2003

BACKGROUND: Platelet components contaminated with bacteria are an important source of transfusion‐associated bacterial sepsis. Estimates of contamination rates vary widely (0–10%) and are highly controversial. The present study, designed with stringent testing regimens, retrospectively determined the prevalence of microbial contaminants in platelets from four collection regions.STUDY DESIGN AND METHODS: During a 9‐month period, outdated platelet units were assayed by spreading aliquots from the unit, and from thioglycollate broth medium inoculated with part of the unit, onto 5‐percent sheep blood agar media. Cultures were examined after 72‐hour incubation at 37°C, and, if bacterial growth was present, the assay processes were repeated with fresh inocula. Units were considered contaminated only if repeatedly positive.RESULTS: Four (0.08%) of 4995 units sampled were contaminated, two with Corynebacterium sp. and one each with Propionibacterium acnes and Aspergillus terreus. Contaminants were present at low, subclinical levels and were detected only after amplification in thioglycollate. The contaminated units were cultured 1, 2, 3, and 7 days after expiration.CONCLUSION: Contamination rates were low and did not vary by region. The identification of A. terreus suggests the role that transfusion may play in transmitting fungal infections should be reassessed. The persistent detection of contaminated platelet units supports the need for a test to detect clinically relevant levels of microbial contaminants in blood components.