bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated RBC exchange transfusion:treatment for cerebral malaria
Authors: Weir E.G. , King K.E. , Ness P.M. , Eshleman S.H.
Published: March 2003

BACKGROUND: Cerebral malaria is a life‐threatening complication of Plasmodium falciparum infection. RBC exchange transfusion can reduce the level of parasitemia in this setting. Experience with automated RBC exchange for cerebral malaria may be limited, as most cases occur when the necessary equipment and blood components are not readily available.

CASE REPORTS: Three patients were admitted with cerebral malaria. Parasites were found in more than 30 percent of RBCs in two cases and in more than 60 percent of RBCs in the third case. Many RBCs contained multiple organisms. In each case, antimalarial therapy was begun, and an automated RBC exchange was performed emergently with a cell separator. Exchange transfusion was repeated within 24 hours for two patients. Parasitemia levels were less than 1 percent in all patients 24 hours after the last exchange. The neurologic status of these patients returned to baseline, and they were discharged 7 to 18 days after admission.

CONCLUSION: Automated RBC exchange transfusion can rapidly reduce the level of parasitemia and restore neurologic functioning in patients with cerebral malaria.
Secretor genotyping for A385T, G428A, C571T, C628T, 685delTGG, G849A, and other mutations from a single PCR
Authors: Svensson L. , Petersson A. , Henry S.M.
Published: March 2003

BACKGROUND: The secretor status of an individual is important for disease relationship studies, because it determines the presence of ABH blood group antigens in the gastrointestinal tract and bodily secretions. Routine serologic methods for determining secretor status are unreliable. Current strategies based on PCR for genotyping require relatively large amounts of DNA and have to be done as several separate experiments.

STUDY DESIGN AND METHODS: A single, multiplex PCR technique followed by RFLP digestion with four restriction enzymes produced unique genotype profiles for most known secretor (FUT2) mutations.

RESULTS: Samples from a range of individuals with common and rare secretor genotypes were analyzed. Each gave unique patterns that allowed secretor genotypes to be determined.

CONCLUSION: By using the method described here and genomic DNA, a secretor genotype based on the FUT2 mutations A385T, G428A, C571T, C628T, 685delTGG, and G849A could be accurately determined.
A hypotonic storage solution did not prolong the viability of RBCs
Authors: Babcock J.G. , Lippert L.E. , Derse‐Anthony C.P. , Mechling M. , Hess J.R.
Published: March 2003

BACKGROUND: Hypotonic storage solutions and WBC filtration are both reported to improve RBC viability. This study tested the ability of an investigational hypotonic storage solution (AS‐24, Medsep Corp.) to extend the viability of liquid‐stored RBCs to 8 weeks.

STUDY DESIGN AND METHODS: In a pair of crossover trials, 11 RBC units, WBC‐reduced by filtration and stored in AS‐24 for 8 weeks, were compared with units from the same donors that were stored for 6 weeks in AS‐3, and 13 RBC units, WBC‐reduced by filtration and stored in AS‐3 for 8 weeks, were compared with units from the same donors that were stored for 6 weeks in AS‐3. Viability was measured by the 51Cr/99mTc double‐isotope method.

RESULTS: RBC viability at 8 weeks averaged 64 ± 3 percent in the AS‐24 units and 67 ± 2 percent in the AS‐3 units. It was equal at 77 ± 3 percent and 77 ± 2 percent after 6 weeks' storage in AS‐3 in both trials.

CONCLUSIONS: Prestorage WBC reduction and storage in AS‐24 did not extend RBC viability to 8 weeks. The improved viability previously demonstrated with storage of dilute suspensions of RBCs in hypotonic solutions is probably caused by factors other than the hypotonicity.
MAM: a “new” high‐incidence antigen found on multiple cell lines
Authors: Montgomery William M. , Nance Sandra J. , Donnelly Sarah F. , Brady Thomas W. , Anderson Garth , Mintz Paul D. , Moulds Marilyn K. , Daniels Geoff L. , Spring Frances A. , Molina Nelly , De Asis Eleanor A. , Olivares Esperanza
Published: March 2003

BACKGROUND: Three women have been identified with an antibody to a “new” high‐incidence antigen found on multiple cell lines.

CASE REPORTS: The proposita, M.A.M., presented during her third pregnancy with an antibody reacting with all RBCs tested except her own. She delivered a thrombocytopenic infant with a 3+ DAT, but without symptoms of HDN. The second example, A.N., presented during her third pregnancy with an antibody reacting with all RBCs tested except her own and those of M.A.M. She delivered a slightly thrombocytopenic but severely anemic infant. The third example, F.K., a sister of A.N., has an antibody reacting with all RBCs tested except her own and those of M.A.M. and A.N.

CONCLUSION: This “new” high‐incidence antigen has been named MAM and assigned high‐incidence antigen number 901016 by the International Society of Blood Transfusion. The corresponding antibody, anti‐MAM, has been shown to cause HDN and has the potential to shorten RBC survival after the transfusion of incompatible RBC units, as determined by monocyte monolayer assay. Immunoblotting and flow cytometry show that this new antibody reacts with various WBC lines in addition to RBCs. This antibody also appears to react with platelets in some assays.
Evaluation of an automated system for the collection of packed RBCs, platelets, and plasma
Authors: Elfath M. Dean , Whitley Pamela , Jacobson May S. , Cranfill‐Hupp Kathy , Kemp Donna M. , McNeil Deanna , Sawyer Sherrie , Bell‐Dize Sharon , Gorlin Jed B. , Kevy Sherwin V. , McAteer Michael J.
Published: March 2003

BACKGROUND: This study evaluated the quality of WBC‐reduced platelets, RBCs, and plasma collected on a new system (Trima, Gambro BCT) designed to automate the collection of all blood components. The study also evaluated donor safety and suitability of these components for transfusion.

STUDY DESIGN AND METHODS: In Phase I, the quality of the components collected on the new system was evaluated by standard in vitro and in vivo testing methods. Results were compared to those from control components collected by currently approved standard methods. In Phase II, additional collections were performed to evaluate the acceptability of the new system and the safety of platelets collected.

RESULTS: In vivo 24‐hour RBC recovery was 76.8 ± 3.1 percent for the test RBC units and 77.1 ± 4.4 percent recovery for whole‐blood (control) RBCs. The differences between test and control platelet results in the in vivo and in vitro assays were not clinically significant. Plasma clotting factors and fibrinogen levels met international standards. The system was well accepted by donors, and no major adverse donor reactions were reported for the 68 procedures performed. No problems were reported with transfusing the blood components collected.

CONCLUSION: Blood components collected with the Trima are equivalent to currently available components, and they meet the applicable regulatory standards. This system provides consistent, standardized components with predictable yields. It provides the option of fully automating the collection of all blood components.
Total hip replacement surgery does not influence RBC survival
Authors: Van Iperen Charlotte E. , Van De Wiel Albert , De Bruin Marcel , Marx Joannes J.M.
Published: March 2003

BACKGROUND: RBC survival may be affected by mechanical or oxidative stress as well as the inflammatory effect of surgery, and thus may contribute to postoperative anemia.

STUDY DESIGN AND METHODS: RBC survival was studied in otherwise healthy patients who underwent total hip replacement (THR). RBCs of five patients scheduled for elective THR surgery were labeled with 51Cr 2 weeks before the surgical procedure. The disappearance of 51Cr‐labeled RBCs was calculated for the preoperative period and for the period from postoperative Day 4 on, when blood loss had ceased.

RESULTS: The half‐life of 51Cr‐labeled RBCs did not change if estimated before (29.0 ± 4.4 days) and after (27.4 ± 3.6 days, p = 0.55) surgery. This indicates that the lifespan of RBCs is not influenced by the surgical procedure.

CONCLUSION: A decrease in RBC survival does not contribute to the pathogenesis of the anemia found after THR surgery.
HCV lookback in the United States:effectiveness of an extended lookback program
Authors: Menozzi Delia , Udulutch Troy , Llosa Augusto E. , Galel Susan A.
Published: March 2003

BACKGROUND: In 1998, the FDA recommended look‐back for HCV. The recommendation was initially limited, however, to donors who reacted on a multiantigen HCV screening test and to components collected since January 1, 1988. A lookback program was extended to include donors who reacted on the first‐generation (single‐antigen) HCV screening test and who were positive on a supplemental assay (RIBA‐1 or ‐2) and all components for which transfusion records could be found (back to 1978).

STUDY DESIGN AND METHODS: The yield of the incremental lookback programs was compared to that originally recommended by the FDA by comparing the number of newly identified HCV‐positive recipients in each program. The results of lookbacks were reviewed on 385 blood components for which 314 transfusion recipients were identified.

RESULTS: Of the 135 recipients in the FDA program, 70 percent were dead, 28 percent were living and notified, and 2 percent could not be located. In the incremental programs, there were 179 recipients, of whom 80.4 percent were dead, 16.2 percent were living and notified, and 3.4 percent could not be located. Most adult recipients were dead (81%), but the majority of pediatric recipients were alive (57%); 76 percent of tested recipients were HCV seropositive, with no significant difference between programs. One‐half of test‐positive recipients in each program were newly identified through the lookback program. Seven of the 20 newly identified HCV‐positive recipients were found through the incremental programs. The yield, defined as newly detected HCV cases per total number of recipients, was 9.6 percent for the FDA and 3.9 percent for the incremental programs. This difference was significant (p = 0.04).

CONCLUSION: The yield of both programs was limited by the high percentage of recipients who had died. Pediatric recipients were more likely to be living at the time of notification. The incremental program was less efficacious than the FDA program in identifying newly HCV‐positive recipients, but one‐third of the newly detected HCV cases were identified through the incremental program.
Detecting failed WBC‐reduction processes:computer simulations of intermittent and continuous process failure
Authors: Adams Melanie R. , Fisher Dennis M. , Dumont Larry J. , Dzik Walter H. , Heaton William A.
Published: March 2003

BACKGROUND: By regulation, ongoing process control of WBC‐reduced processes is performed on 1 percent of WBC‐reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer‐generated “residual WBC” distributions, sample size sensitivity to continuous or intermittent WBC‐reduction failure was examined.

STUDY DESIGN AND METHODS: Populations of log‐normally distributed values (mean ± SD, 4.5 ± 0.5; n = 105) were generated. Continuous failure (log‐normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admixing increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria.

RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90‐percent confidence, and only if individual WBC values were compared to cutoff.

CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low‐variance normal distribution, the detection of a high‐variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC‐reduction process failure, as well as clinically relevant quality limits.
Selecting donors of platelets for refractory patientson the basis of HLA antibody specificity
Authors: Petz Lawrence D. , Garratty George , Calhoun Loni , Clark Bill D. , Terasaki Paul I. , Gresens Christopher , Gornbein Jeffrey A. , Landaw Elliot M. , Smith Randy , Cecka J. Michael
Published: March 2003

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.
Primitive human HPCs are better maintained and expanded in vitro at 1 percent oxygen than at 20 percent
Authors: Ivanović Zoran , Sbarba Persio Dello , Trimoreau Franck , Faucher Jean‐Luc , Praloran Vincent
Published: March 2003

BACKGROUND: The liquid culture of murine bone marrow cells at 1‐percent oxygen maintains the balance between primative progenitor cell renewal and clonogenic progenitor expansion better than that at 20‐percent oxygen. These results are of potential interest for the ex vivo expansion of human progenitor cells, as low O2 tension could preserve the engraftment potential of cultured apheresis products.

STUDY DESIGN AND METHODS: G–CSF‐mobilized blood cells collected by apheresis, now the main source of progenitor cells for autologous transplantation, were cultured at 1‐percent and 20‐percent O2 for 7 days in serum‐free liquid cultures in the presence of IL‐3 and SCF (5 ng/mL). The growth of the clonogenic progenitors (CFU–GM, BFU–E, CFU–Mix) and of the more primitive human HPCs that are capable of generating clongenic progenitors in secondary liquid culture, as well as the proliferation and differentiation of total and CD34+ cells, was analyzed.

RESULTS: The expansion of CD34+ cells and of clonogenic progenitors was significantly lower in liquid cultures at 1‐percent O2 than at 20‐percent O2. On the contrary, the primitive human HPCs were better maintained and expanded at 1‐percent O2, although the number of CD34+ cells remaining quiescent was lower. After 7 days of liquid culture at 1‐percent or 20‐percent O2 the percentage of CD34+ cells was similar. However, the CD34+ cells that divided more than four times (PKH2 staining) were more numerous in liquid cultures incubated at 1‐percent O2.

CONCLUSION: When cultured at 1‐percent O2 for 7 days in presence of IL‐3 and SCF, the CD34+ cells present in apheresis components underwent more cell divisions and better maintained their primitive progenitor cell potential. As suggested by previous results in mice, our data on human cells emphasize the potential interest of cultures at low O2 tension (1%) for cell therapy protocols aimed at expanding primitive HPCs in autografts.
Donor age‐related differences in PBPC mobilization with rHuG–CSF
Authors: De la Rubia Javier , Díaz Miguel A. , Verdeguer Amparo , Pascual Maria J. , Arbona Cristina , Arrieta Rosario , Brunet Salut , Bargay Joan , Martínez Carmen , Espigado Ildefonso , Serrano David , Alegre Adrián , De Arriba Felipe , De la Serna Javier , Zamora Concha , Benlloch Luis , Sanz Miguel A.
Published: March 2003

BACKGROUND: Data on the administration of rHuG–CSF to normal donors <18 years old are very limited.

STUDY DESIGN AND METHODS: The results of rHuG–CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors ≥18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1‐17) and 38 (18‐71) years, respectively (p<0.001). The mean dose of rHuG–CSF was 10 μg per kg per day (range, 9‐16) during a mean of 5 days (range, 4‐6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001).

RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 × 106 per kg of donor′s body weight in Group A and B, respectively. Fifty‐six percent of Group A donors needed only one apheresis to achieve ≥4 × 106 CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001).

CONCLUSION: The administration of rHuG–CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.
A randomized controlled trial oftransfusion‐related acute lung injury: is plasma from multiparous blood donors dangerous?
Authors: Palfi Miodrag , Berg Sören , Ernerudh Jan , Berlin Gösta
Published: March 2003

BACKGROUND: Transfusion‐related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double‐blind, crossover study.

STUDY DESIGN AND METHODS: Intensive care patients, judged to need at least 2 units of plasma, were randomly assigned to receive a unit of control plasma and, 4 hours later, a plasma unit from a multiparous donor (≥3 live births) or to receive the plasma units in opposite order. The patients were closely monitored, and body temperature, blood pressure, and heart rate were recorded. Blood samples for analysis of blood gases, TNFα, IL‐1 receptor antagonist, soluble E selectin, and C3d complement factor were collected at least on four occasions (before and after the transfusion of each unit).

RESULTS: Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFα concentrations than transfusion of control plasma. The mean arterial pressure increased significantly after the transfusion of control plasma, whereas plasma from multiparous donors had no effect on it. Five posttransfusion reactions were observed in 100 patients, in four cases after the transfusion of plasma from multiparous donors.

CONCLUSION: Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients.
A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins
Authors: Lee Douglas C. , Stenland Christopher J. , Miller Jeanette L.C. , Cai Kang , Ford Elizabeth K. , Gilligan Kevin J. , Hartwell Randal C. , Terry Jarrett C. , Rubenstein Richard , Fournel Michael , Petteway Stephen R.
Published: March 2003

BACKGROUND: Experimental evidence from rodent models indicates that blood can contain transmissible spongiform encephalopathy (TSE) infectivity, which suggests a potential risk for TSE transmission via proteins isolated from human plasma. Because methods that can reduce TSE infectivity typically are detrimental to protein function, infectivity must be removed to ensure the safety of these therapeutic proteins. Animal bioassays are conventionally used to detect infectivity, but the pathogenic form of the prion protein (PrPSc) can serve as a marker for TSE infectivity.

STUDY DESIGN AND METHODS: Seven plasma protein‐purification steps were performed after the plasma intermediates were spiked with TSE‐infected material. Resulting fractions were analyzed for PrPSc by using a Western blot assay and for TSE infectivity by using an animal bioassay. Western blots were quantitated by an endpoint dilution analysis, and infectivity titers were calculated by the Spearman‐Kärber method.

RESULTS: PrPSc partitioning paralleled TSE infectivity partitioning, regardless of the nature of the protein‐purification step. The detection ranges for PrPSc and infectivity were 0 to 5.3 log and 1.1 to 8.9 log median infectious dose per unit, respectively. Clearance of PrPSc and infectivity ranged from 1.0 to 6.0 log.

CONCLUSION: Purification steps for isolating therapeutic proteins from human plasma showed the removal of both PrPSc and TSE infectivity. PrPSc partitioning coincided with infectivity partitioning, which showed a close relationship between PrPSc and TSE infectivity. By exploiting this association, the in vitro Western blot assay for PrPSc was valuable for estimating the partitioning of TSE infectivity during plasma protein purification.
Optimizing pretransfusion antibody detection and identification:a parallel, blinded comparison of tube PEG,solid‐phase, and automated methods
Authors: Bunker Mark L. , Thomas Christine L. , Geyer Stanley J.
Published: March 2003

BACKGROUND: The ideal pretransfusion testing strategy identifies maximal significant antibodies at minimal cost. Objectives of this study were to compare the characteristics of three testing methods and determine their optimal incorporation into the following generic testing sequence: 1) screen, for antibodies 2) if results are positive, use primary identification method, 3) if results are inconclusive, use secondary identification method.

STUDY DESIGN AND METHODS: A total of 2000 consecutive, unselected, coded specimens were tested with three screening methods—PEG IAT, manual and automated solid phase red cell adherence assay (SPRCA). Of 202 positive results, 187 were of sufficient volume and were tested with both PEG and manual SPRCA identification panels, yielding 82 with significant antibodies, plus one that was negative by both methods found on retrospective review of nonstudy results. Calculations were made on the 1985 volume‐sufficient specimens, simulating the possible testing permutations.

RESULTS: Manual SPRCA was the most sensitive antibody screen (67/83 = 81%) and the least specific (1840/1902 = 97%); automated SPRCA was the least sensitive (54/83 = 65%) and most specific (1883/1902 = 99%); and PEG was intermediate in both sensitivity (64/83 = 77%) and specificity (1860/1902 = 98%). Of the identification panels, manual SPRCA identified more antibodies than PEG (67 versus 66) but had more inconclusive results (41 versus 20). Of overall strategies, manual SPRCA screening with either sequence of identification methods identified the most antibodies (66). The combination of PEG screen, PEG identification, and manual SPRCA identification identified slightly fewer antibodies (63) but had the lowest reagent cost, total (reagent plus labor) cost, and cost per antibody identified. The sequence of automated SPRCA screening with manual SPRCA identification, and PEG identification had the lowest hands‐on time.

CONCLUSIONS: The most cost‐effective pretransfusion strategy is PEG screen with PEG identification, plus manual SPRCA identification when PEG identification is inconclusive.
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
Authors: Valeri C. Robert , Ragno Gina , Pivacek Linda E. , Srey Rithy , Hess John R. , Lippert Lloyd E. , Mettille Frank , Fahie Roland , O'Neill E. Mary , Szymanski Irma O.
Published: March 2003

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.

STUDY DESIGN AND METHODS: Studies were performed at three military sites and two civilian sites. Each site performed in vitro testing of 20 units of RBCs. In addition, one military site and two civilian sites conducted autologous transfusion studies on ten units of previously frozen, deglycerolized RBCs that had been stored at 4°C in AS‐3 for 15 days. At one of the civilian sites, 10 volunteers received autologous transfusions on two occasions in a randomized manner, once with previously frozen RBCs that had been stored at 4°C in AS‐3 for 15 days after deglycerolization and once with liquid‐preserved RBCs that had been stored at 4°C in AS‐1 for 42 days.

RESULTS: The mean ± SD in vitro freeze‐thaw‐wash recovery value was 87 ± 5 percent; the mean ± SD supernatant osmolality on the day of deglycerolization was 297 ± 5 mOsm per kg of H2O, and the mean ± SD percentage of hemolysis after storage at 4°C in AS‐3 for 15 days was 0.60 ± 0.2 percent. The paired data from the study of 10 persons at the civilian site showed a mean ± SD 24‐hour posttransfusion survival of 76 ± 6 percent for RBCs that had been stored at 4°C for 15 days after deglycerolization and 72 ± 5 percent for RBCs stored at 4°C in AS‐1 for 42 days. At the three sites at which 24‐hour posttransfusion survival values were measured by three double‐label procedures, a mean ± SD 24‐hour posttransfusion survival of 77 ± 9 percent was observed for 36 autologous transfusions to 12 females and 24 males of previously frozen RBCs that had been stored at 4°C in AS‐3 for 15 days after deglycerolization.

CONCLUSION: The multicenter study showed the acceptable quality of RBCs that were glycerolized and deglycerolized in the automated ACP 215 instrument and stored in AS‐3 at 4°C for 15 days.
Quantitative and genotypic analysis of TT virusinfection in Chinese blood donors
Authors: Zhong Sheng , Yeo Winnie , Lin Che Kit , Lin Xiao‐Rong , Tang Mandy W. , Johnson Philip J.
Published: March 2003

BACKGROUND: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified.

STUDY DESIGN AND METHODS: Sera from 471 healthy blood donors (aged 11‐58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC‐PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection.

RESULTS: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC‐PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 × 102 copies per mL to 6 × 104 copies per mL, with a median value of 1.2 × 104 copies per mL. Sequencing and phylogenetic analysis of a 223‐bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60‐percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found.

CONCLUSION: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.
Partial expression of RHc on the RHD polypeptide
Authors: Faas Brigitte H.W. , Beuling Esther A. , Ligthart Peter C. , Van Rhenen Dick J. , Van Der Schoot C. Ellen
Published: March 2003

BACKGROUND: In the human Rh blood group system, c is, after D, the most immunogenic antigen.

STUDY DESIGN AND METHODS: The background of a new partial c phenotype (Dc), identified on the RBCs of two unrelated white persons, was studied. This was done by analyzing the reactivity of the RBCs from the donors with anti‐c reagents, by performing sequence analysis, and by carrying out transduction studies.

RESULTS: Serologic results suggested the existence of a new partial c phenotype. Genomic DNA and cDNA analysis revealed a normal RHCe allele, a normal RHD allele, and an RHD allele that carried two point mutations: 307T>C and 329T>C (the latter known to be associated with the DVII, Tar‐positive phenotype). No normal RHc allele was found. Thus, it was most likely that c is encoded by the mutated RHD allele (phenotype DDcCCee). Indeed, subsequent transduction of K562 erythroleukemic cells with an RHD cDNA carrying the 307T>C point mutation (leading to S103P) resulted in the expression of c.

CONCLUSION: In the human Rh system, P103 is involved in the expression of c. Moreover, c can be expressed in vivo on the D polypeptide.
A comparative study of the postoperative allogeneicblood‐sparing effects of tranexamic acid and of desmopressin after total knee replacement
Authors: Zohar Edna , Fredman Brian , Ellis Martin H. , Ifrach Nisim , Stern Avraham , Jedeikin Robert
Published: March 2003

BACKGROUND: Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet‐induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet‐induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought.

STUDY DESIGN AND METHODS: A prospective, single‐blind study of 40 patients undergoing TKR was performed. In the tranexamic acid (TA) group, in the 30 minutes before the limb tourniquet was deflated, an IV bolus dose of TA (15 mg/kg) was administered. Thereafter, a constant IV infusion of 10 mg per kg per hour was administered until 12 hours after tourniquet deflation. In the desmopressin group, desmopressin (0.3 mg/kg) and saline were administered by a similar protocol. No blood was administered intraoperatively. A postoperative Hct <27 percent constituted the postoperative transfusion trigger. Patients were examined daily for signs of lower‐limb deep vein thrombosis, and they underwent lower‐limb Doppler ultrasound on postoperative Day 5. Three months after surgery, the incidence of delayed thromboembolic events was assessed.

RESULTS: During the first 12 postoperative hours, blood accumulation in the surgical drain was significantly (p<0.05) lower in the TA group (162 mL ± 129) than in the desmopressin group (342 mL ± 169). From the sixth postoperative hour until 3 days postoperatively, Hct levels were significantly lower in the desmopressin group than in the TA group. Significantly more allogeneic blood was transfused in the desmopressin group (11 patients received 16 units) than in the TA group (3 patients each received 1 unit) (p<0.02). There were no clinical signs of deep vein thrombosis or abnormal Doppler ultrasound studies. Three months postoperatively, there were no thromboembolic events among the 37 patients interviewed.

CONCLUSION: TA induces better blood sparing than desmopressin. Therefore, a tourniquet‐induced increase in fibrinolysis is the likely cause of delayed bleeding after TKR surgery. However, before routine administration, the effect of TA on the incidence of thromboembolic events requires further investigation.
Molecular basis of the Dombrock null phenotype
Authors: Rios Maria , Hue‐Roye Kim , Storry Jill R. , Lee Terry , Miller Jeffery L. , Reid Marion E.
Published: March 2003

BACKGROUND: The Dombrock blood group system consists of two antithetical antigens, Doa and Dob, and three high‐incidence antigens, Gregory (Gya), Holley (Hy), and Joseph (Joa). The null phenotype of the Dombrock blood group system (Donull) was identified when it was found that Gy(a–) RBCs also lack Doa, Dob, Hy, and Joa.

STUDY DESIGN AND METHODS: DNA from three Gy(a–) persons was analyzed. PCR products for each of the three DO exons and their flanking intronic regions were sequenced in both directions. The cDNA from two of the people was subjected to PCR using primers in exon 1 and exon 3, and the products were sequenced.

RESULTS: The Donull phenotype is associated with a single nucleotide mutation in the acceptor splice site of DO (IVS1–2a>g), which results in outsplicing of exon 2.

CONCLUSION: Outsplicing of exon 2 is predicted to cause a –1 frameshift and a premature stop codon. Any product of such a transcript would lack the glycosyl‐phosphatidylinositol‐anchor motif, and RBCs would be devoid of the Do glycoprotein.
Transfusing methylene blue‐photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate
Authors: Atance Rosa , Pereira Arturo , Ramírez Begoña
Published: March 2003

BACKGROUND: Photodynamic virus inactivation of plasma with methylene blue significantly decreases the recovery of fibrinogen and coagulation factors V and VIII. Because an adequate supply of fibrinogen is essential for the therapeutic efficacy of transfused plasma in many clinical settings, it was plausible that transfusing photoinactivated plasma (PIP) instead of FFP would result in an increased demand for plasma and cryoprecipitate.

STUDY DESIGN AND METHODS: The study involved a retrospective analysis of the use of plasma at a university hospital (Barcelona, Spain) over three 1‐year periods: one before the implementation of PIP therapy and two after. Blood components transfused to plasma recipients were listed by broad diagnostic categories based on the Diagnosis‐Related Group classification.

RESULTS: During the period under study, 2,967 patients were given plasma in this hospital. They received 27,434 units of plasma, 1,660 of cryoprecipitate, 10,079 of platelets, and 24,607 of packed RBCs. Patients undergoing surgical procedures accounted for 74 percent of all transfused plasma. In 71 percent of patient admissions, packed RBCs were transfused in addition to plasma. Diagnostic categories with the greatest requirement for plasma were cardiac valve surgery, liver transplant, wounds and traumatic injuries, and bowel surgery. The use of PIP was associated with a 56‐percent increase in the aggregated demand for plasma, whereas the transfusion of non‐virusinactivated cryoprecipitate increased twofold the first year and threefold the second year. The growth in the use of plasma took place in all the diagnostic categories. In those categories that include patients with liver disease, a partial substitution of PIP for cryoprecipitate was observed during the second year after PIP therapy implementation.

CONCLUSION: The use of PIP was associated with a marked increase in the demand for plasma and cryoprecipitate, which probably was due to the low hemostatic quality of the new component. It is possible that such an increase overrode the potential health benefits derived from transfusing virus‐inactivated plasma.
The use of genotyping to predict the phenotypes of human platelet antigens 1 through 5 and of neutrophil antigens in Taiwan
Authors: Chu Chen‐Chung , Lee Hui‐Lin , Chu Thomas Weitao , Lin Marie
Published: March 2003

BACKGROUND: The human platelet antigen (HPA) 1 through 5 and the human neutrophil antigen (HNA‐1) systems are relevant to immune‐related thrombocytopenia and neutropenia. The alloantigen distribution profiles in the population will aid in estimating the risk of alloimmunization.

STUDY DESIGN AND METHODS: Genotyping of the genes that control the expression of the HPA‐1 through ‐5 and HNA‐1 systems in Taiwanese (n = 326) and Taiwan's indigenous peoples (n = 608) was performed by PCR with the sequence‐specific primer (PCR‐SSP) method.

RESULTS: In the HPA system, HPA‐1b and HPA‐4b were absent among Taiwan's indigenous tribes and detected among other Taiwanese only with frequencies of <0.2 percent and <0.5 percent, respectively. The GP1BA*2 (HPA‐2b) and GP1A*2 (HPA‐5b) allele frequencies range from 1 percent to 7 percent and 0.4 percent to 3.5 percent among the two ethnic groups, respectively. GP2B*1 (HPA‐3a) and GP2B*2 (HPA‐3b) showed similar allele frequencies. In the HNA‐1 system, the FCGR3B*1 (HNA‐1a) allele frequency was about twice that of FCGR3B*2 (HNA‐1b) in Taiwanese and also in most of the indigenous tribes. Three FCGR3B (HNA‐1) null persons were found in one indigenous tribe (Ami tribe), for an FCGR3B null frequency of 19.8 percent. However, no FCGR3B*3 (HNA‐1c) allele was detected in Taiwan.

CONCLUSION: The frequencies of HPA‐1b, ‐2b, and ‐5b in the Taiwanese population were much lower than those among whites. In Taiwan, all of the HNA‐1 null found was due to the deletion of the FCGR3B gene, and this deletion may be widely distributed in the Ami tribe.
Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure
Authors: Streiff Michael B. , Ness Paul M.
Published: March 2003

BACKGROUND: FV inhibitors are a largely preventable iatrogenic coagulopathy in which the frequency is increasing in clinical practice.

STUDY DESIGN AND METHODS: Three cases associated with our institution are reported. A systematic review of the MEDLINE database was performed, and reference lists were reviewed to identify relevant publications.

RESULTS: One hundred twenty‐six cases of FV inhibitors have been reported in the world's literature. Eighty‐seven have been reported in the last decade, of which two thirds are due to exposure to bovine thrombin. Bovine thrombin‐associated FV antibodies develop in 40 to 66 percent of cardiac surgery patients and in 20 percent of neurosurgery patients. Thirty‐three percent of reported patients developed bleeding complications. Inhibitors persisted on average 2.3 months. Standard coagulation assays do not reliably predict clinical manifestations. Multimodality therapy, including immunosuppression, is useful for treatment of symptomatic patients.

CONCLUSIONS: FV inhibitors are a common complication of bovine thrombin exposure that can have devastating clinical consequences. Transfusion medicine specialists and hematologists can play a critical role in reducing the incidence of FV inhibitors by educating the medical community about safer alternative fibrin sealants.
Molecular background of D(C)(e) haplotypes within the white population
Authors: Noizat‐Pirenne France , Le Pennec Pierre‐Yves , Mouro Isabelle , Rouzaud Anne‐Marie , Juszczak Geneviève , Roussel Michèle , Lauroua Pierre , Krause Claire , Rouger Philippe , Cartron Jean‐Pierre , Ansart‐Pirenne Hélène
Published: March 2003

BACKGROUND: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e.

STUDY DESIGN AND METHODS: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low‐frequency antigens of the Rh (RH) system and other non‐Rh low‐frequency antigens. Neither Hor+, Mol+ nor Hor+, Mol– RBCs expressed the V (RH10), VS (RH20), and/or Rh32 (RH32) low‐frequency antigens. These results suggested that Hor+, Mol+ variants expressed Rh33 (RH33 or Har) and FPTT (RH50), whereas Hor+, Mol– variants might express an undefined low‐frequency antigen. Further serologic and molecular analyses were performed.

RESULTS: Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe‐D(5)‐Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so‐called RHCeVA allele). The presence of exon 5RHD resulted in several amino acid alterations predicted in the external loop 4 of the CeVA polypeptide. Molecular analysis of Hor+, Mol– variants revealed the presence of a new RHCe allele characterized by a single point mutation C340T within exon 3 (the so‐called RHCeMA allele), resulting in a R114W substitution predicted on the external loop 2 of the CeMA polypeptide. A serologic study showed a different pattern of reactivity with C and e MoAbs.

CONCLUSION: Two types of mutations resulted in amino acid substitutions predicted in external loops 4 and 2, respectively, which altered both the C and e reactivity, and indicated conformation changes or defective interaction between nonadjacent loops of the Ce polypeptide. Serologic analysis showed that together with Hor and Mol sera testing, the use of different C and e MoAbs could help to identify these variants within the white population.
Acquired and transient RBC CD55 deficiency (Inab phenotype) and anti‐IFC
Authors: Matthes Thomas , Tullen Emanuelle , Poole Joyce , Banks Jackie , Nagy Monika , Stelling Marie‐Jose , Boehlen Françoise , Michel Martine , Beris Photis , Hustinx Hein , Crew Vanja , Daniels Geoff
Published: March 2003

BACKGROUND: Antigens of the Cromer blood group system reside on the glycoprotein CD55 (decay‐accelerating factor). The Inab phenotype is the null phenotype of this system. So far, only five propositi have been described who exhibit this phenotype, and single‐nucleotide substitutions in the CD55 gene have been found in three of them. This report describes the first example of a patient with an acquired and transient form of the Inab phenotype.

CASE REPORT: A 54‐year‐old black patient was admitted to the hospital because of abdominal pain. Multiple splenic infarctions were visualized in the abdominal computerized tomography scan, and a prophylactic splenectomy was performed. The patient's serum reacted by an IAT with all donor RBCs tested.

RESULTS: Serologic analysis showed that the patient had the rare Inab phenotype and that his serum contained anti‐IFC. Flow cytometry demonstrated the absence of CD55 on his RBCs, whereas lymphocytes, monocytes, granulocytes, and platelets expressed CD55, albeit at a weaker level than cells of common phenotypes. cDNA revealed no differences from the published sequences. Flow cytometry performed 12 months after splenectomy showed reappearance of the CD55 antigen; serologic tests performed after 17 months revealed that the anti‐IFC had almost disappeared and that the RBCs were again agglutinated by various Cromer antibodies.

CONCLUSION: A patient with an acquired and transient form of the Inab phenotype is described, in whom the CD55 deficiency is limited to the RBCs and is associated with splenic infarctions.
An improved serodiagnostic test for Chagas' disease employing a mixture of Trypanosoma cruzi recombinant antigens
Authors: Umezawa Eufrosina S. , Bastos Sueli F. , Coura Jose R. , Levin Mariano J. , Gonzalez Antonio , Rangel‐Aldao Rafael , Zingales Bianca , Luquetti Alejandro O. , Da Silveira Jose Franco
Published: March 2003

BACKGROUND
: Blood transfusion is one of the most important transmission routes of Chagas' disease, a major parasitic infection in Latin America. Therefore, screening for antibodies to
Trypanosoma cruzi is mandatory in blood banks in South America. Most of the commercial serologic tests employ epimastigote antigens and show a high number of inconclusive and false‐positive results, with high economic and social costs.

STUDY DESIGN AND METHODS
: An ELISA using a mixture of three
T. cruzi recombinant antigens, B13, 1F8, and H49 (mix‐ELISA), was evaluated, first with a panel of well‐characterized sera from 617 patients with Chagas' disease and 277 nonchagasic individuals, living in nine countries of South and Central America. Subsequently, the mix‐ELISA was evaluated with 451 samples, from an endemic area of Brazil (Goiás), that were rejected from several blood banks because they presented discrepant results by two commercially available kits (indirect immunofluorescence assay, indirect hemagglutination assay, and/or ELISA).

RESULTS : The mix‐ELISA exhibited 99.7 percent sensitivity and 98.6 percent specificity in the first evaluation with the 894 samples. In the second evaluation, 451 sera that had discrepant results in the first screening for Chagas' disease were further analyzed with the mix‐ELISA. Upon consideration of the consensus results obtained with the trypomastigote excreted‐secreted antigens blot test, a confirmatory test for Chagas' disease, the mix‐ELISA led to a reduction in 99.6 percent in the number of discordant sera.

CONCLUSION
: The combination of three
T. cruzi recombinant antigens in a multiantigen immunoassay was highly sensitive and specific for Chagas' disease diagnosis. It is proposed that it can be applicable in blood bank screening in conjunction with the conventional serologic tests.
Enigma Variations on History in Three Keys: A Conversational Essay
Authors: Dening Greg
Published: March 2003

Book reviewed in this article:

History In Three Keys: The Boxers as Event, Experience, and Myth by Paul A. Cohen.
Mad History Disease Contained?Postmodern Excess Management Advice from the UK
Authors: Kansteiner Wulf
Published: March 2003

Book reviewed in this article:

In Defence of History, by Richard J. Evans.