bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion‐dependent patient
Authors: Hersh J.K , Horn E.G. , Brecher M.E. 
Published: March 2003

BACKGROUND:It is known that in vivo platelet survival varies as the platelet count changes. Previous attempts at curve fitting fail to predict the decreased platelet survival in thrombocythemia. Therefore, mathematical relations that more closely approximate platelet survival were derived and used in models of platelet transfusion practice.STUDY DESIGN AND METHODS:A differential equation for platelet loss was derived that included a constant (constant homeostatic loss), a first‐ order term (senescent loss), and a second‐order term (one proportional to the square of the platelet concentration and whose contribution is expected to be significant only at higher platelet concentrations). Data derived from this model was compared to platelet survival data in normal, thrombocytopenic, and thrombocythemic patients and to the platelet decay after high‐dose chemotherapy. To provide further validation of this model, predicted and actual platelet requirements were calculated or obtained (chart review) in bone marrow patients with uncomplicated thrombocytopenia after ablation and at two platelet‐ transfusion thresholds (20 and 10 × 10(9)/L).RESULTS:The equations accurately modeled normal, thrombocytopenic, and thrombocythemic platelet survival. Chart review demonstrated a 12.5 percent reduction in platelet transfusion requirements when the transfusion threshold was reduced from 20 to 10 × 10(9) per L. The model predicted a reduction of 14.0 percent. For 100 days of uncomplicated thrombocytopenia and a transfusion threshold of 10 × 10(9) per L, transfusion of 3 units of platelet concentrates compared to a 6‐unit pool of platelet concentrates, resulted in a 22‐percent savings of platelet units. CONCLUSION: Platelet survival as a function of platelet concentration can be modeled by use of a differential equation. This model challenges current dogma regarding platelet destruction and predicts decreased platelet survival in thrombocythemic patients. The model illustrates that large doses of platelets would result in greater time between transfusions, however, more units of platelets are used. Consideration should be given to the more frequent use of smaller doses of platelets in patients who chronically require platelet transfusion support.
Lowering the hemoglobin cutoff for female plateletpheresis donors
Authors: Fraser J. L. , Whatmough A. , Uhl L. , Kruskall M. S. 
Published: March 2003

BACKGROUND: The standards of the American Association of Blood Banks describe a minimum hemoglobin level of 12.5 g per dL for apheresis donors. Until 1995, the authors' institution accepted occasional platelet donors with a lower minimum hemoglobin (11.5 g/dL), if accompanied by medical director approval.STUDY DESIGN: All donation records from a 6‐month period before 1995 were retrospectively reviewed to determine whether this lower hemoglobin cutoff adversely affected either the safety of the platelet donation process or donors' subsequent hemoglobin levels.RESULTS: Of 450 donations, 56 (12%, Group 1) were from donors with hemoglobin concentrations between 11.5 and 12.4 g per dL (2 donations from 1 man; 54 donations from 45 women). The remaining 394 donations (88%, Group 2) came from donors with hemoglobin concentrations > or = 12.5 g per dL (216 donations from 118 men; 178 donations from 119 women). The frequency of donor reactions was acceptable (Group 1, 11%; Group 2, 6%); 2 percent of donations by Group 1 donors and 1 percent by Group 2 donors were terminated because of these reactions. Of 46 donors in Group 1, 30 returned to donate platelets again at a later time; at least once, 23 (77%) had a hemoglobin > or = 12.5 g per dL. Ten donors in Group 1 returned for additional donations within 56 days; no meaningful decrease in hemoglobin levels occurred. A hemoglobin cutoff of 12.5 g per dL during the study period would have excluded 1 percent of platelet donations by men and 23 percent by women.CONCLUSION: The data demonstrate that the lower hemoglobin cutoff of 11.5 g per dL is a safe and relevant threshold for accepting female plateletpheresis donors and would allow more participation by women in blood donor programs.
Infection by an unenveloped DNA virus associated with non‐A to ‐G hepatitis in Japanese blood donors with or without elevated ALT levels
Authors: Itoh K. , Hirakawa K. , Okamoto H. , Ukita M. , Tanaka H. , Sawada N. , Tsuda F. , Miyakawa Y. , Mayumi M. 
Published: March 2003

BACKGROUND: An unenveloped, single‐stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non‐A to ‐G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels.STUDY DESIGN AND METHODS: A total of 861 blood donors without previous transfusions and who were negative for markers of hepatitis B or C virus infection were tested. DNA of the TT virus was detected by polymerize chain reaction with hemi‐nested primers.RESULTS: TT virus DNA was detected in 62 of 280 (22.1% [95% CI: 18.1‐26.6]) donors with elevated ALT levels (mean ± SD, 89.3 ± 36.4 U/L; range, 61‐301 U/L), which is significantly more frequently (p<0.02) than its detection in 91 of 581 (15.7% [95% CI: 13.2‐18.4]) donors with normal ALT (<45 U/L). The frequency of TT virus DNA increased with age, in donors with and without elevated ALT.CONCLUSION: The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non‐A to ‐G hepatitis.
Factor VIII/von Willebrand factor complex in methylene blue‐treated fresh plasma
Authors: Aznar J.A. , Molina R. , Montoro J.M. 
Published: March 2003

BACKGROUND: The effect of virus inactivation of fresh plasma with methylene blue has been studied on the factor VIII/von Willebrand factor molecular complex (FVIII/vWF), factor XIII, and fibrinogen.STUDY DESIGN AND METHODS: FVIII function or activity, vWF activity, vWF antigen, vWF:Ag, vWF multimeric structure, fibrinogen, and factor XIII were analyzed in paired samples of control fresh plasma (untreated) and the same fresh plasma treated with methylene blue. Treated plasma was filtered (0.8‐1.2 μm), mixed with a methylene blue solution (300 μg/L), and illuminated at 50,000 lux for 30 minutes on both sides.RESULTS: Average loss of biologic activity of coagulation factors studied was 25 percent (FVIII function, 29%; fibrinogen, 39%; factor XIII, 16%; and vWF activity, 18%). Reduction in vWF activity was significantly lower than that in FVIII function (p<0.05), and the vWF multimeric structure did not show alterations.CONCLUSION: Methylene blue‐treated plasma and the cryoprecipitates obtained from it may be effective for replacement therapy in cases of von Willebrand disease and deficiencies of factor XIII and fibrinogen, but the clinical studies are needed to verify that possibility.
Transfusion‐related acute lung injury due to granulocyte‐agglutinating antibody in a patient with paroxysmal nocturnal hemoglobinuria
Authors: Żupańska B. , Uhrynowska M. , Konopka L. 
Published: March 2003

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is usually reported after the transfusion of blood components from donors with white cell (WBC) antibodies, but only very rarely if the patient has these antibodies. The pathogenesis of TRALI is not fully understood. Not all transfusion recipients develop TRALI, even though WBC antibodies are present in the donor or the recipient.CASE REPORT: A patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed TRALI after the transfusion of non‐WBC‐reduced red cells is described. Granulocyte‐agglutinating anti‐5b was detected in his serum, and the crossmatch with the donor granulocytes was positive. The patient also developed a severe exacerbation of hemolysis with renal failure; serologic results excluded an immune hemolytic posttransfusion reaction. The patient recovered from both events after about 1 week.CONCLUSION: Granulocyte‐agglutinating antibodies present in the recipient play an important role in TRALI, and also other factors may contribute to its pathogenesis. The reaction between the PNH patient's antibody (anti‐5b) and transfused WBCs was found not only to be responsible for the respiratory distress but also to have triggered, through the innocent‐bystander mechanism of complement activation, an intensive hemolysis, which was very likely a contributing factor in the development of TRALI.
Quality and clinical response to transfusion of prestorage white cell‐reduced apheresis platelets prepared by use of an in‐line white cell‐reduction system
Authors: Elfath M. , Tahhan H. , Mintz P. , Dumont L. , Whitley P. , Sawyer S. , McNeil D. 
Published: March 2003

BACKGROUND: This study evaluated the quality and clinical effectiveness of white cell (WBC)‐reduced apheresis platelets collected by the use of a new technology, fluidized particle‐bed separation.STUDY DESIGN AND METHODS: In phase I, six suitable donors underwent two separate plateletpheresis procedures on one occasion, each separated by less than 10 minutes. In random order, a control unit was collected with the COBE Spectra and a test unit with the Spectra Leukocyte‐Reduction System (LRS). The quality of apheresis platelet components was assessed by an in vitro test panel, and residual WBCs were counted by Nageotte chamber and flow cytometric methods. For the in vivo studies, the test and control units were randomly labeled with either 51Cr or 111In at the end of storage and transfused simultaneously to the donor. Samples were taken for calculation of platelet survival and recovery. In phase II, 109 thrombocytopenic patients were given platelets collected by use of the Spectra LRS.RESULTS: Test platelets had significantly fewer residual WBCs (median 7.6 × 104) than control platelets (median 3.9 × 105), with equivalent in vitro function values. Test and control platelets had similar recovery and survival. Transfused platelets collected by use of the LRS achieved a mean 1‐hour corrected‐count increment of 19.3.CONCLUSION: The LRS collects platelet components with significantly lower WBC contamination without adverse effects on the function or in vivo survival of the platelets.
Pressure cycling technology:a novel approach to virus inactivation in plasma
Authors: Bradley D.W. , Hess R.A. , Tao F. , Sciaba‐Lentz L. , Remaley A.T. , Laugharn J.A. , Manak M. 
Published: March 2003

BACKGROUND: Hydrostatic‐pressure virus inactivation is a novel approach to the inactivation of pathogens in plasma and blood‐derived components, that retains the therapeutic properties of these products.STUDY DESIGN AND METHODS: A custom‐built apparatus was used to pressurize human plasma samples spiked with lambda phage. Phage titer and plasma protein activities were monitored after pressure treatment.RESULTS: Pressure‐mediated inactivation of lambda phage was found to be an effective means for virus inactivation, particularly when performed at near‐zero (0°C) temperatures, rather than at temperatures above 20°C and below –40°C. The efficiency of inactivation was improved by an increase in applied pressure and repeated cycling from atmospheric to high pressure. In contrast, activities of plasma proteins alkaline phosphatase and total amylase did not vary with temperature and remained within 29 percent and 6 percent, respectively, of starting values after the same pressure treatments. By combining cycling, near‐zero temperatures, and high pressure, phage titers in serum were reduced approximately 6 log after 10 to 20 minutes of treatment. Activities of plasma proteins IgG, IgM, and factor X were at 104 percent, 89 percent, and 80 percent, respectively, of starting values after 20 minutes of the same temperature and pressure treatment.CONCLUSION: High‐pressure procedures may be useful for the inactivation of viruses in blood and other protein‐containing components.
Amino acid substitutions in human erythroid protein band 3 account for the low‐incidence antigens NFLD and BOW
Authors: McManus K. , Pongoski J. , Coghlan G. , Zelinski T. 
Published: March 2003

BACKGROUND: The low‐incidence red cell antigens NFLD (700.37) and BOW (700.46) were first described in 1984 and 1988, respectively. Recent investigations showed that antigens of the Diego blood group system (including a number of low‐incidence antigens) are coded by SLC4A1 (solute carrier family 4, anion exchanger member 1 gene). Among these newly characterized Diego system antigens is Wu (designated DI9). Because a serologic relationship among Wu, NFLD, and BOW has been established, a series of genetic and molecular investigations of SLC4A1 in relation to NFLD and BOW were undertaken.STUDY DESIGN AND METHODS: By the use of exon‐specific primers, single‐strand conformational polymorphism (SSCP) analysis of SLC4A1 was performed on DNA isolated from an NFLD+ person from Japan, from the members of a Canadian kindred segregating for NFLD, and from two unrelated BOW+ persons. Exons displaying SSCPs were subjected to genetic linkage analysis (for NFLD only) and DNA sequencing.RESULTS: SSCPs in DNA amplified from exons 12 and 14 of SLC4A1 were observed for all NFLD+ subjects. Linkage between each of these polymorphisms and NFLD was established with peak lods = 4.82 at θ = 0.00 for combined paternal and maternal meiosis. DNA sequencing of exons 12 and 14 of SLC4A1 from NFLD+ persons identified A→T and C→G mutations that underlie Glu429Asp and Pro561Ala substitutions in human erythroid band 3 protein (band 3). DNA from the two unrelated BOW+ persons only exhibited an SSCP in exon 14 of SLC4A1. Subsequent DNA sequencing revealed a C→T mutation that accounts for a Pro561Ser substitution in band 3.CONCLUSION: SLC4A1 codes for the low‐incidence red cell antigens NFLD and BOW. In light of these findings, both antigens have been assigned to the Diego blood group system.
Incidence and clinical presentation of posttransfusion TT virus infection in prospectively followed transfusion recipients: emphasis on its relevance to hepatitis
Authors: Wang J.T. , Lee C.Z. , Kao J.H. , Sheu J.C. , Wang T.H. , Chen D.S. 
Published: March 2003

BACKGROUND: A novel transfusion‐transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion.STUDY DESIGN AND METHODS: Serial serum samples collected as part of a prospective study of posttransfusion hepatitis were examined for TTV DNA by a nested PCR assay.RESULTS: Among 150 adults undergoing cardiac surgery, posttransfusion specimens from 59 individuals were positive for TTV DNA. Pretransfusion sera were found to be positive in 13 of these individuals. Therefore, 46 (33.6%) of the 137 previously uninfected patients developed new TTV viremia after transfusion. Among the 46 patients, 3 were coinfected with HCV, 5 were coinfected with HGV, and 38 were infected with TTV alone. No apparent symptoms or signs were noted in the 38 patients infected by TTV alone or the 5 infected with HGV plus TTV. The average peak serum ALT activity was 31 IU per L, with persistently normal levels in 34 of the 38 patients with TTV infection alone. In 8 other patients who subsequently developed well‐documented non‐A‐G hepatitis, 3 were positive for TTV (3/8 vs. 46/137, p = 0.8). In 12 patients followed for more than 1 year, TTV viremia persisted in every case.CONCLUSION: In this population, TTV is transmitted by transfusion to approximately 30 percent of patients who undergo cardiac surgery. Most of the infections appear to become persistent. Despite the high prevalence rate, TTV does not appear to cause hepatitis on its own.
Heparin‐induced coagulopathy associated with staphylococcal protein A immunoadsorption treatment columns: an in vitro and in vivo analysis
Authors: Kunkel J.F. , Sarode R. , Verba M. , Yomtovian R. 
Published: March 2003

BACKGROUND: The staphylococcal protein A (SPA) column used to treat refractory autoimmune and alloimmune thrombocytopenia and rheumatoid arthritis patients is primed with heparin to prevent possible fibrin clot formation when the patient's plasma is passed through the column. A BMT patient with refractory alloimmune thrombocytopenia had prolonged activated partial thromboplastin times (aPTTs) at the end of SPA column treatments. This observation led to in vivo and in vitro analysis of the kinetics of heparin elution from the SPA column.STUDY DESIGN AND METHODS: Two patients with refractory rheumatoid arthritis, who were treated on five occasions with the SPA column (as a part of a national trial) primed with 5000 U of heparin, were monitored for aPTT and heparin in their plasma. In addition, two in vitro analyses were performed with FFP for heparin elution from the SPA column.RESULTS: The in vivo studies showed the presence of 0.3 to 1.5 U per mL of heparin in patients' plasma at the end of the SPA column treatments that corresponded with the prolonged aPTTs. The in vitro studies showed that 82 to 85 percent heparin (approx. 4400 U) was eluted from the SPA column during rather than before the procedure.CONCLUSION: Patients undergoing SPA column treatments, especially those with thrombocytopenia, may be at increased risk of bleeding as a result of the presence of a significant amount of heparin in their circulation during the entire period of SPA column treatment.
V(D)J germline gene repertoire analysis of monoclonal D antibodies and the implications for D epitope specificity
Authors: Perera W.S. , Moss M.T. , Urbaniak S.J. 
Published: March 2003

BACKGROUND: The D antigen is a highly immunogenic human RBC antigen. Alloimmunization against the D antigen produces high‐affinity antibodies that cause hemolytic transfusion reactions and HDN.STUDY DESIGN AND METHODS: Cloning and subsequent sequence analysis of 11 new samples of monoclonal anti‐D was performed in an attempt to identify V(D)J germline gene usage. Sequences were compared and analyzed with 37 previously published samples of anti‐D for identification of VH and VL pairings, canonical structures, and conformation of restricted germline gene usage.RESULTS: The VH and VL pairings used by the new D MoAbs resulted in seven canonical combinations, three of which had not been described previously. Preferential usage of gene segments from the VH3 and VH4 families and of D3, D6, JH6, and DPK9 germline gene segments was also determined. Three samples of anti‐D from different donors were found to use similar VH and Vκ germline genes, despite the fact that two of the antibodies recognized epD6/7 and the third recognized epD1. From the cumulative analysis of the anti‐D IgG, 24 VH and VL gene pairings were identified, resulting in only 10 canonical structures.CONCLUSIONS: Despite the potential for diversity, only a minority of VH and VL germline genes are used by anti‐D. Consequently, VH and VL pairings and the resulting canonical structures are similarly restricted.
Correlation of in vivo and in vitro functions of fresh and stored human platelets
Authors: Rothwell S.W. , Maglasang P. , Reid T.J. , Gorogias M. , Krishnamurti C. 
Published: March 2003

BACKGROUND: Long‐term storage of human platelets has been hindered by the loss of function of the platelets stored under current protocols. Novel preservation methods have encouraged examination of platelet function of cells preserved by cooling and freezing. The function of the platelets was assessed by using both in vitro assays and an in vivo rabbit bleeding model.STUDY DESIGN AND METHODS: Human platelets were stored in the presence or absence of 2 μM cytochalasin B and 80 μM EGTA/AM at 4°C for 14 days or by freezing in the presence or absence of 5 percent DMSO. After the storage period, the platelets were resuspended in normal saline and infused into rabbits. Platelet function was assessed in vivo in a kidney bleeding model and in vitro by platelet‐induced clot retraction and by platelet aggregation.RESULTS: Platelets stored at either 4°C or ‐145°C exhibited shorter survival times in the rabbit circulation than did fresh platelets. Platelets cooled to 4°C, in both the presence or absence of cytochalasin B and EGTA/AM treatment, or frozen in the absence of DMSO were not effective in halting bleeding. However, frozen DMSO‐treated platelets were as effective as fresh platelets in stopping bleeding. In vitro assays showed that cooled platelets treated with cytochalasin B and egtazic acid/AM and frozen DMSO‐treated platelets retained 30 to 40 percent platelet function, while the cooled and frozen control samples exhibited no platelet‐induced clot retraction. With thrombin as the agonist, only frozen DMSO‐treated platelets exhibited a tendency to aggregate, although at only 22 percent of the aggregation function of fresh platelets.CONCLUSION: It is possible to freeze platelets and retain in vivo efficacy if the cryopreservative DMSO is included in the preparation. In vitro responses were greatly reduced by all of the storage protocols, but it may not be necessary to retain 100 percent in vitro function to have a platelet substitute or storage product that functions satisfactorily in vivo.
Separation of dendritic cells from highly purified human monocytes by counterflow centrifugation induces tissue factor expression
Authors: Broussas Matthieu , Cornillet‐Lefebvre Pascale , Bernard Jacky , Adjizian Jean‐C. , Potron Gérard , Nguyên Philippe 
Published: March 2003

BACKGROUND: In vitro generation of dendritic cells (DCs) from human monocytes represents a promising tool in immunotherapy. However, it is not known whether the separation of DCs from monocytes induces tissue factor expression and therefore may trigger coagulation in patients receiving these DC preparations. The aim of this study is thus to analyze tissue factor expression on monocyte‐derived DCs and to compare their ability to trigger thrombin generation to that of macrophages obtained from the same monocytes.STUDY DESIGN AND METHODS: Human monocytes are separated by leukapheresis and washed by using counterflow centrifugation in sterile, endotoxin‐free conditions. Macrophages are grown from human monocytes in the presence of GM–CSF alone and immature DCs are grown in the presence of GM–CSF plus IL‐4 for 5 days with fetal calf serum (IDC‐FCS). Immature DCs are also grown from human monocytes for 7 days in the presence of GM–CSF plus IL‐4 with human group AB serum (IDC‐HS). The addition of prostaglandin E2 and TNFα in this culture medium at Day 5 leads to mature DCs (MDC‐HS). Tissue factor mRNA expression is studied by RT‐PCR analysis. Tissue factor antigen is measured by ELISA in cell lysates and by direct flow cytometry. The procoagulant activity of intact cells is assessed by using an amidolytic assay or a chronometric assay.RESULTS: IDC‐FCS express tissue factor mRNA and antigen and trigger thrombin generation. Procoagulant activity of IDC‐FCS is dependent on both tissue factor expression and exposure to anionic phospholipid. Monocyte‐derived macrophages cultured for 5 days with GM–CSF alone express lower levels of tissue factor mRNA, tissue factor antigen, and procoagulant activity than IDC‐FCS. IDC‐HS and MDC‐HS also express high levels of tissue factor mRNA and antigen and support procoagulant activity.CONCLUSION: Monocyte‐derived DCs express a high level of functional tissue factor and support procoagulant activity. This finding should be taken into account in clinical trials.