bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐base substitutions give rise to a five‐banded DNA profile at the D10S28 locus
Authors: Allen R.W. , Sanford‐Sharp C.E.
Published: March 2003

Background: DNA profiles from variable number of tandem repeat (VNTR) loci typically are composed of two bands, one derived from each member of the homologous pair of chromosomes. DNA profiles composed of more than two bands result from mutations, and the uestion arises as to the mechanism underlying these unusual multibanded DNA profiles.

Study Design and Methods: An alleged father in a paternity test was found to have a five‐banded DNA profile at the D10S28 locus when his DNA was subjected to single‐locus restriction fragment length polymorphism mapping with the restriction enzyme Pvu II.

Results: Several results suggest that this complex DNA profile is the result of several single change within the VNTR locus First, there was no evidence of partial digestion of the DNA with Pvu II. Furthermore, the multibanded allele happened, in this case, to be transmitted to the child, who also showed a five‐banded pattern composed of four bands inherited from the alleged father and one band inherited from the mother. Second, digestion of this DNA with Hae III resulted in the visualization of just two bands at the D10S28 locus.

Conclusion: The results confirm the notion that mutations at VNTR loci are not always the result of additions or deletions of tandem repeats, but that they can also involve single‐base substitutions either within or flanking VNTR loci that give rise to atypical DNA profiles and new alleles at the locus. single‐base changes within or flanking VNTR loci that give rise to a typical DNA profiles and new alleles at the locus.
Transfusion transmission of retroviruses: human T‐lymphotropic virus types I and II compared with human immunodeficiency virus type 1
Authors: Donegan E. , Lee H. , Operskalski E.A. , Shaw G.M. , Kleinman S.H. , Busch M.P. , Stevens C.E. , Schiff E.R. , Nowicki M.J. , Hollingsworth C.G. , Mosley J.W. ,   The Transfusion Safety Study Group
Published: March 2003

Background: The incidence of transfusion transmission of human T‐ lymphotropic virus type I (HTLV‐I) and HTLV type II (HTLV‐II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV‐1). The effects of refrigerator storage of the blood component on infectivity of the viruses needs definition.

Study Design and Methods: The circumstances influencing the transmission of HTLV‐I, HTLV‐ II, and HIV‐1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti‐HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing.

Results: Overall, 27 percent (26/95) of the recipients of blood components from anti‐HTLV‐ I‐ and ‐II‐positive donors became infected (9 with HTLV‐I and 17 with HTLV‐II). No recipients of acellular blood components became infected with HTLV‐I or ‐II. There was no probable transmission by components stored > 10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti‐HIV‐1‐positive blood were infected regardless of component type, and no effect on transmission occurred with storage for < 26 days.

Conclusion: Transfusion‐ transmitted HTLV‐I and ‐II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate.
Platelet bacterial contamination and the use of a chemiluminescence‐ linked universal bacterial ribosomal RNA gene probe
Authors: BRECHER M.E. , HOGAN J.J. , BOOTHE G. , KERR A. , MCCLANNAN L. , JACOBS M.R. , YOMTOVIAN R. , CHONGOKOLWATANA V. , TEGTMEIER G. , HENDERSON S. , PINEDA A. , HALLING V. , KEMPER M. , KURAMATO K. , HOLLAND P.V. , LONGIARU M.
Published: March 2003

BACKGROUND: Currently, the maximum outdate for platelets is 5 days, because of the increasing chance of bacterial growth over time. Various methods for rapid detection of bacterial contamination of blood components have been described, with mixed results and no general acceptance. A recently described, molecular biologic approach for the detection of bacterial contamination involves a chemiluminescence‐ linked universal DNA bacterial probe to a highly conserved bacterial region of ribosomal RNA (rRNA).

STUDY DESIGN AND METHODS: A multicenter trial of a chemiluminescence‐linked universal bacterial rRNA probe for the detection of bacterial contamination in platelet concentrates is described. At each of five sites, platelet concentrates (no older than 1 day from date of phlebotomy) were inoculated in triplicate with isolates of four bacterial species (Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus epidermidis, and Staphylococcus aureus) to a final concentration of 10 to 50 colony‐forming units (CFUs) per mL and in triplicate to a final concentration of 1000 CFUs per mL. At one site, an additional 6 platelet concentrates were inoculated with sterile saline to serve as controls. Inoculated units were then subjected periodically to quantitative cultures and probe analyses. A total of 126 platelet concentrates were studied over a period of 7 days (120 inoculated with bacteria and 6 with sterile saline).

RESULTS: This assay was, in some cases, able to detect S. aureus bacterial contamination in the range of 100 to 1000 CFUs per mL; the majority of samples (B. cereus, P. aeruginosa, S. aureus, and S. epidermidis) with contamination exceeding 10(4) CFUs per mL; and all samples with contamination of 2.1 × 10(5) CFUs per mL or greater. Increasing the sample size from the recommended 0.4 mL to 1.0 mL resulted in an unacceptable loss of specificity (83.3%).

CONCLUSION: The routine use of this assay would be expected to result in a decreased risk of septic platelet transfusion reactions and could lead to a lengthening of the current 5 day storage period for platelets. Further, the pooling of random‐donor platelet concentrates before storage instead of immediately before transfusion may be possible if this rRNA probe is employed to detect bacteria in the pool.
A multicenter evaluation of reproducibility of swirling in platelet concentrates
Authors: BERTOLINI F. , MURPHY S. ,   Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion
Published: March 2003

BACKGROUND: Eleven laboratories participated in a study investigating whether swirling can be used in monitoring platelet discoid morphology in platelet concentrates (PCs).

STUDY DESIGN AND METHODS: In each laboratory, two readers observed the swirling pattern in 1‐ to 5‐day‐ old PCs, in PCs containing spherical platelets obtained by 4 degrees C storage (spherical PCs), and in PCs containing known proportions of spherical and discoid platelets. Swirling was reported as positive, intermediate, or negative. Moreover, platelet morphology was evaluated by oil‐phase microscopy.

RESULTS: Swirling of spherical PCs was found to be positive and negative in 5 and 68 percent of cases, respectively. Conversely, swirling of fresh PCs was positive and negative in 83 and 2 percent of cases, respectively. Results in PCs containing known amounts of added spherical platelets were intermediate between those in fresh and spherical PCs. The observed agreement between the two readers (number of concordant readings/total readings) was 67 percent. Most disagreements concerned positive versus intermediate or intermediate versus negative evaluations, whereas a positive versus negative disagreement was observed in only 1 percent of cases. The percentages of discs found by microscopy showed greater variation among the different laboratories, indicating that this measurement should be better standardized.

CONCLUSION: Evaluation of swirling seems promising for large‐scale quality control of PCs. Further studies are needed to confirm this hypothesis.
Low cytokine contamination in buffy coat‐derived platelet concentrates without filtration
Authors: Flegel W.A. , Wiesneth M. , Stampe D. , Koerner K.
Published: March 2003

BACKGROUND: Cytokines (interleukin [IL]‐1 beta, IL‐6, and tumor necrosis factor [TNF]) generated by white cells during the storage of platelet concentrates can cause febrile nonhemolytic transfusion reactions. The high rate of febrile reactions reported in other studies was not observed in the patients in the authors' center. This discrepancy prompted the determination of cytokine levels in buffy coat‐ derived platelet concentrates.

STUDY DESIGN AND METHODS: Platelet concentrates were produced from buffy coats by a standard large‐scale production process. Buffy coats were separated from the red cell and plasma components, and then platelets were recovered from the buffy coats by a soft‐spin procedure. Levels of cytokines (IL‐1 beta, IL‐6, IL‐8, and TNF) were determined with commercial enzyme‐linked immunosorbent assays.

RESULTS: In platelet concentrates produced by the buffy coat method, IL‐1 beta, IL‐6, IL‐8, and TNF were observed at or below the detection limit of current enzyme‐linked immunosorbent assays after 5 days' storage at 22 +/− 2 degrees C. Therefore, prestorage filtration had no measurable effect on cytokine levels. In controls, IL‐ 1 beta, IL‐6, IL‐8, and TNF were quantitatively detected after exogenous addition of recombinant cytokines or exposure to lipopolysaccharide.

CONCLUSION: Platelet concentrates prepared from buffy coats may be virtually free of cytokines (IL‐1 beta, IL‐6, IL‐8, and TNF) during 5 days of storage. Filtration is not required to reduce the recipient's cytokine exposure via such platelet concentrates.
Low risk of viral infection after administration of vapor‐heated factor VII concentrate or factor IX complex in first‐time recipients of blood components. International Factor Safety Study Group
Authors: Shapiro A. , Abe T. , Aledort L. M. , Anderle K. , Hilgartner M. W. , Kunschak M. , Preston F. E. , Rivard G. E. , Schimpf K. ,   The International Factor Safety Study Group
Published: March 2003

BACKGROUND: Vapor‐heated human factor VII concentrate and human factor IX complex are both obtained from prothrombin complex, undergo similar methods of manufacture, and are subjected to an identical two‐step vapor‐heating process for virus inactivation. STUDY DESIGN AND METHODS: Intermediate‐purity vapor‐heated human factor VII concentrate and vapor‐ heated human factor IX complex were monitored for safety with regard to viral infection in the context of an International Factor Safety Study, a prospective study that follows the revised recommendations from the International Congress of Thrombosis and Hemostasis (ICTH). Because the rarity of the respective hereditary deficiencies would have made separate analyses unrealizable, the results were combined for the final analysis. Entry required that patients have no history of transfusion with any blood derivative. After the first infusion of the study drug, patients were monitored for 6 months for the development of non‐A, non‐ B hepatitis (NANBH) and infection with hepatitis B virus (HBV) and for 15 months for infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). An event was defined as a positive result on any test for any infection. An alanine aminotransferase level more than 2.5 times the upper limit of normal on two consecutive occasions was defined as an event for NANBH. HBV infection was monitored with tests for three different HBV markers: the HBV surface antigen, antibody against the HBV surface antigen, and antibody against HBV core antigen. HCV and HIV infection were monitored with tests for HCV and HIV antibodies. RESULTS: The 25 patients who completed the study (1 has not completed the study and 1 dropped out) received a total of 434 infusions comprising 17 different production lots of the concentrates. Twenty patients were analyzable for NANBH and 25 for HCV and HIV infection. Since most patients had been given HBV vaccination, only 4 patients were analyzable for this end point. None of the patients showed evidence of having developed an event. These data satisfy ICTH criteria when the products are considered together, but vapor‐heated factor VII concentrate does not qualify alone because there were only five patients in this group. CONCLUSION: Vapor‐heated factor VII concentrate and vapor‐heated factor IX complex are associated with a low risk of viral infection. Preliminary results are also presented, indicating that the concentrates are safe with regard to inhibitor development.
The chemical and immunoglobulin structural features necessary for reactions of quinine‐dependent antibodies to neutrophils
Authors: Stroncek D. F. , Herr G. P.
Published: March 2003

BACKGROUND: Previously described were three patients with quinine‐ dependent antibodies to neutrophils, platelets, and red cells who had episodic pancytopenia and renal failure. The nature of the antibody‐ drug‐neutrophil interactions was investigated with sera from these patients. STUDY DESIGN AND METHODS: Sera from all three patients were tested against neutrophils in flow cytometry in the presence of several compounds related to quinine. IgG and Fab and F(ab')2 fragments were prepared from the serum of one patient and tested against neutrophils in flow cytometry and immunoprecipitation in the presence of quinine and related compounds. RESULTS: In flow cytometry, sera from all three patients plus quinidine reacted with neutrophils. Sera from Patients 1 and 3 reacted with neutrophils in the presence of cinchonidine (desmethoxy‐quinine) and serum from Patient 3 also reacted with neutrophils in the presence of cinchonine (desmethoxy‐quinidine). None of the sera reacted with neutrophils in the presence of chloroquine or primaquine. Serum from Patient 3 plus quinolinic acid, a tryptophan metabolite, reacted with neutrophils, but sera from the other two patients did not. Patient 3 serum plus tryptophan or another tryptophan metabolite, quinalidic acid, did not react with neutrophils. IgG from Patient 3 serum reacted with neutrophils in flow cytometry in the presence of quinine, quinidine, cinchonidine, cinchonine, and quinolinic acid. F(ab')2 fragments plus quinine or cinchonidine also reacted with neutrophils, but Fab fragments plus quinine did not. In the presence of quinine, Patient 3 IgG immunoprecipitated the 85‐ and 60‐kDa molecules and F(ab')2 fragments immunoprecipitated the 85‐kDa molecule. Patient 3 serum plus quinidine, cinchonidine, cinchonine, and quinolinic acid immunoprecipitated the 130‐ and 85‐kDa molecules, but not the 60‐kDa molecule. CONCLUSION: Quinine‐dependent neutrophil antibodies often react with neutrophils in the presence of quinidine and related compounds. These reactions were mediated by the F(ab')2 domain of IgG.
Infectious disease markers in blood donors in northern Thailand
Authors: Mundee Y. , Kamtorn N. , Chaiyaphruk S. , Nantachit N. , Ness P. M. , Nelson K. E.
Published: March 2003

BACKGROUND: A major epidemic of human immunodeficiency virus type 1 (HIV‐1) infections that are primarily due to heterosexual transmission has developed in Thailand since 1988. The epidemic has been most severe in northern Thailand. The blood banks in Chiang Mai began screening donors for HIV‐1 antibodies in February 1988 and for p24 antigen in April 1992. STUDY DESIGN AND METHODS: The trends of HIV‐1 antibody prevalence were analyzed by type of donor (i.e., paid, replacement, and voluntary) for the period of 1988 through 1993. In addition, the prevalence of HIV‐1 p24 antigen and of antibodies to syphilis, hepatitis B surface antigen, and hepatitis C virus was evaluated among blood donors at Chiang Mai University Hospital and the Thai Red Cross blood banks in Chiang Mai. RESULTS: The prevalence of HIV‐1 antibodies increased from 0.84 percent in 1988 to 4.04 percent in 1991. Seropositivity was highest in paid professional donors. After discontinuation of the use of paid donors in 1993, HIV‐1 antibody prevalence decreased to 3.34 percent. Antibody prevalence in replacement donors increased from 0.56 percent in 1988 to 5.82 percent in 1991. Among 44,446 donors tested, 7 (0.016%) were HIV‐1 p24 antigen positive but antibody negative. CONCLUSION: The exclusion of paid donors and the use of p24 antigen testing are justified in northern Thailand. Additional strategies to exclude donors at very high risk and to attract those at low risk for infection should be developed and evaluated to increase blood transfusion safety in this and other, similar populations.
Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol‐anchored protein that carries Gregory, Holley, and Dombrock blood group antigens
Authors: Rao Neeraja , Udani Manisha , Nelson Julie , Reid Marion E. , Telen Marilyn J.
Published: March 2003

BACKGROUND: The high‐frequency Hy and Gya antigens have been shown to reside on the same protein. Gy(a‐) Hy‐negative red cells are also Do(a‐ b‐). A mouse monoclonal antibody, 5B10, was produced with specificity related to the human Gregory, Holley, and Dombrock blood group antigens. STUDY DESIGN AND METHODS: The antibody reacted in direct hemagglutination assays, and its specificity was investigated by radioimmunoassay, inhibition assay, and Western blotting. RESULTS: The 5B10 antibody failed to bind to abnormal paroxysmal nocturnal hemoglobinuria red cells and human erythroleukemia cell line K562, but it was weakly reactive with HEL cells. Red cells, but not other circulating hematopoietic cells, express the 5B10 antigen. The 5B10 antibody had a specificity similar but not identical to that of Gya. Gy(a‐) Hy‐negative red cells reacted extremely weakly with 5B10 antibody, but Gy(a‐) Hy‐negative red cells treated with a variety of proteases bound 5B10 antibody strongly. This suggests that these cells express a variant form of the protein recognized by 5B10. CONCLUSION: Identification of a monoclonal antibody to this glycosylphosphatidylinositol‐linked protein opens a new avenue for investigation of the biochemistry, genetics, and function of the glycosylphosphatidylinositol‐linked protein that bears the Gya, Hy, and Do antigens.
Multiple or uncommon red cell alloantibodies in women: association with autoimmune disease
Authors: Ramsey G. , Smietana S. J.
Published: March 2003

BACKGROUND: Patients with multiple or uncommon red cell (RBC) alloantibodies require special efforts in the blood bank. This study investigated whether such persons had other immune‐related conditions that might help to explain or predict their propensity for RBC antibody formation.

STUDY DESIGN AND METHODS: Charts were retrospectively reviewed of 29 men and 83 women with multiple (> or = 3) RBC antibodies of potential clinical significance, uncommon RBC antibodies (anti‐e, ‐ Kpb, ‐Jkb, ‐Fyb, ‐S, ‐U, ‐Yta, ‐Dib, ‐Ata), or both. The clinical features in 43 women with multiple antibodies were compared to those in two equal‐sized control cohorts of women matched for transfusion‐ related diagnoses, but having either one RBC antibody or none.

RESULTS: Women with uncommon RBC antibodies had a 33‐percent (18/54) prevalence of autoimmune disease. Twenty‐eight percent of the 43 women with multiple antibodies had autoimmune disease, compared to 14 percent of women in the cohort with one RBC antibody (p = 0.09) and 7 percent of those in the cohort without RBC antibodies (p = 0.01). Only one of the 29 men had autoimmune disease.

CONCLUSION: Autoimmune disease is a common underlying factor in women who make multiple or uncommon RBC alloantibodies of potential clinical significance.
Efficacy of autologous fresh whole blood or platelet‐rich plasma in adult cardiac surgery
Authors: Triulzi D.J. , Gilmor G.D. , Ness P.M. , Baumgartner W.A. , Schultheis L.W.
Published: March 2003

BACKGROUND: Transfusing fresh autologous blood during cardiac surgery may improve hemostasis and decrease the need for transfusion.

STUDY DESIGN AND METHODS: A prospective randomized study was performed with fresh whole blood (WB) obtained by intraoperative hemodilution (IH) and with platelet‐rich plasma (PRP) obtained by perioperative apheresis from adult cardiac surgery patients.

RESULTS: Seventy patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH arm, and 28 to serve as controls. A mean of 924 +/− 130 mL of WB was collected from the IH group, and a mean of 650 +/− 124 mL of PRP was collected from the PRP group (mean, 1.42 +/− 0.74 × 10(11) platelets); these components were transfused after bypass. Preoperative measures were similar among groups. Intraoperatively, the groups did not differ in bypass time, estimated blood loss, number of transfusions, or proportion receiving transfusion(s). Postoperatively, control patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP]; p = 0.014), but there was no difference in the proportion of patients requiring red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the length of hospitalization (p = 0.57).

CONCLUSION: Although a hemostatic benefit manifested as reduced postoperative bleeding was observed, this study does not support the use of fresh blood components obtained by IH or PRP collection during low‐risk cardiac surgery. Additional studies are needed to assess whether more aggressive component collection or the use of these techniques in high‐ risk cases may have a greater impact on clinical outcome variables, including transfusion.
Preoperative autologous blood donation: benefit or detriment? A mathematical analysis
Authors: Cohen J.A. , Brecher M.E.
Published: March 2003

BACKGROUND: Advocates of preoperative autologous blood donation (PABD) often fail to consider the needs of individual patients and the effects of donation on hematocrit. Mathematical modeling is used here to analyze PABD.

STUDY DESIGN AND METHODS: A model of PABD was constructed to simulate the transfusion of red cells once a predetermined minimum hematocrit was reached. Preoperatively deposited units not needed to maintain a hematocrit at this level were not transfused. Final hematocrits were compared to the hematocrit that would be expected if the patient had not donated blood for his or her own operative use.

RESULTS: For many patients, particularly those with normal initial hematocrits, large estimated blood losses must occur before the minimum hematocrit is reached. It is also known that patients donating multiple units typically cannot maintain their baseline hematocrit. In such cases, for blood losses of any volume, the final hematocrit was lower if units were collected preoperatively and transfusion did not occur. Preoperatively donating patients are more likely to be transfused earlier and more frequently than nondonating patients. Derived figures, based on individual patient values, help predict which patients will benefit most from PABD.

CONCLUSION: PABD may actually lead to decreased postoperative hematocritis (with enhanced risk of ischemia) and otherwise unnecessary transfusions.
Carboplatin‐induced immune hemolytic anemia
Authors: Marani T. M. , Trich M. B. , Armstrong K. S. , Ness P. M. , Smith J. , Minniti C. , Sandler S. G.
Published: March 2003

BACKGROUND: A case of acute hemolysis following therapy with carboplatin, an anticancer chemotherapeutic agent, was investigated. Hemolytic anemia has been associated with cisplatin, a related drug, but not with carboplatin. CASE REPORT: An 8‐year‐old boy was treated for an astrocytoma by monthly intravenous injections of carboplatin. Lower back pain was noted after 26 monthly injections, and overt intravascular hemolysis occurred after the 27th injection. The direct antiglobulin test was 4+ with anti‐IgG and 1+ with anti‐C3d. RESULTS: Blood samples obtained on Days 28 and 56 after the last injection were tested for carboplatin‐dependent antibody. The direct antiglobulin test was 1+ with anti‐IgG; the eluate was 1+ with and without carboplatin. The serum indirect antiglobulin test was negative in the absence of carboplatin, 3+ to 4+ in the presence of carboplatin, and 1+ with carboplatin‐coated cells. Day 56 serum antibody titer was 64 (agglutination at 37 degrees C), 512 (indirect antiglobulin test) in the presence of carboplatin, and 8 (indirect antiglobulin test) with carboplatin‐coated cells. CONCLUSION: The findings indicate a carboplatin‐induced antibody reacting in vitro by a complex mechanism combining elements of “immune complex,” drug adsorption, and autoantibody mechanisms. Drug‐dependent hemolysis is a previously unreported but potentially serious complication of carboplatin therapy.
Prevention of chemotherapy‐induced anemia by the use of erythropoietin in patients with primary malignant bone tumors (a double‐blind, randomized, phase III study)
Authors: Wurnig C. , Windhager R. , Schwameis E. , Kotz R. , Zoubek A. , Stockenhuber F. , Kurz R. W.
Published: March 2003

BACKGROUND: Patients undergoing chemotherapy for treatment of malignancy frequently experience clinically significant anemia. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been effectively introduced in anemic patients suffering from chronic renal failure. The present study was designed to assess, first, whether rHuEPO treatment decreases transfusion requirements in chemotherapy‐induced anemia and, second, whether high‐dose rHuEPO application is safe.

STUDY DESIGN and METHODS: Thirty consecutive anemic patients (hemoglobin <11 g/dl) receiving combination chemotherapy for primary malignant bone tumors were studied in a prospective, double‐blind, randomized, Phase III trial. Patients received chemotherapy according to one of two German protocols, depending on histologic diagnosis. All subjects enrolled were randomly assigned either to receive 600 IU of rHuEPO per kg of body weight intravenously twice a week or to receive a placebo during chemotherapy. To obtain comparable data, an observation period of 20 weeks was chosen. Twenty‐nine patients fulfilled the criteria and were eligible for statistical evaluation.

RESULTS: Transfusion requirements were significantly decreased from Week 8 of therapy (p<0.05) in the treatment group. Therapeutic benefits were even more evident with continuation of therapy (Week 12, p = 0.03; Week 16, p = 0.016; Week 20, p = 0.002). The blood required was 2.1 units of red cells in the treatment group and 8.4 units of red cells in the placebo group. All patients tolerated rHuEPO with no serious side effects.

CONCLUSION: These findings suggest that rHuEPO is an effective and well‐tolerated therapeutic option for decreasing the transfusion requirements in chemotherapy‐induced anemia.
Antigen testing for human immunodeficiency virus (HIV) and the magnet effect: will the benefit of a new HIV test be offset by the numbers of higher risk, test‐seeking donors attracted to blood centers? Retrovirus Epidemiology Donor Study
Authors: Korelitz J.J. , Busch M.P. , Williams A.E. ,   the Retrovirus Epidemiology Donor Study
Published: March 2003

Background: There currently is debate on whether to include new assays for viral antigens and nucleic acids in the battery of screening tests applied to all blood donations. Proposals call for implementation of p24 antigen screening tests to help identify donors who are infected with human immunodeficiency virus type 1 (HIV‐1) but have not yet seroconverted (window‐period donors). There is concern, however, that people at higher risk for HIV infection will be attracted to blood centers in order to obtain the results of an HIV assay that is not routinely available elsewhere. Therefore, the benefit of antigen testing may be offset by an increase in the HIV incidence rate among blood donors.

Study Design and Methods: Estimates were obtained from previous reports for the HIV incidence rate among blood donors, the percentage of donations from test‐seeking donors, the duration of the HIV‐infectious window period, and the performance of p24 antigen screening assays. Sensitivity analyses were performed by using various percentages of test‐seeking donors following implementation of antigen testing and various HIV incidence rate ratios of test‐seekers to nonseekers. Hypothetical residual HIV risks were calculated for multiple scenarios and compared to the current estimate of HIV risk without antigen screening of blood donations.

Results: If antigen testing reduces the window period by 27 percent (e.g., from 22 days to 16 days), and the HIV incidence rate among test‐seekers is 30 times that among nonseekers, then the benefit of antigen testing will be eliminated if the percentage of test‐seekers (currently estimated at 3.2%) increases to 5.7 percent. If antigen testing reduces the window period by approximately 45 percent (e.g., from 22 days to 10 days or from 13 days to 6 days) and the HIV incidence rate ratio (test‐seekers vs. nonseekers) is assumed to be equal to the HIV prevalence ratio (5.3), then the percentage of donations from test‐seeking donors would have to increase to 25 percent of all donations to offset the benefit of antigen screening.

Conclusion: This model helps identify the key measures for assessing the potential adverse effect of increased test seeking as a consequence of the addition of p24 antigen (or other direct virus) assays to blood donor screening programs. In most scenarios, the beneficial effect of antigen screening exceeded the potential detrimental effect of attracting higher‐risk, test‐seeking donors. The possibility cannot be ruled out, however, that a subgroup of high‐risk, test‐seeking donors attracted to the blood centers by a new HIV test will offset the reduction in the residual risk of HIV infection associated with antigen screening.
Coexistent IgG2 and IgA deficiencies in blood donors
Authors: Sandler S.G. , Trimble J. , Mallory D.M.
Published: March 2003

Background: To meet the transfusion requirements of IgA‐deficient patients with anti‐IgA, blood services screen random donors to identify potential donors of IgA‐deficient blood components. New information reveals that some IgA‐deficient persons may also be deficient in IgG2 and may be at increased risk for bacterial infections.

Study Design and Methods: Serum samples from IgA‐deficient blood donors and patients were tested for IgG2 concentration by radial immunodiffusion using monospecific anti‐IgG2.

Results: Four (9.0%) of 44 IgA‐deficient blood donors and 14 (31.5%) of 44 IgA‐deficient patients had coexistent IgG2 and IgA deficiencies. Follow‐up interviews with the 4 donors who had coexistent IgG2 and IgA deficiencies revealed that 3 had recurrent respiratory infections and had been hospitalized at least once for pneumonia. The fourth donor did not report a history suggestive of recurrent infections.

Conclusion: Some blood donors, recruited specifically because they are IgA deficient, may also be deficient in IgG2. Persons identified by donor screening programs as being IgA deficient should be tested for IgG2. If deficient in IgG2, they should be evaluated for a history of recurrent bacterial infections and counseled accordingly.
Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering
Authors: Webb I.J. , Coral F.S. , Andersen J.W. , Elias A.D. , Finberg R.W. , Nadler L.M. , Ritz J. , Anderson K.C.
Published: March 2003

Background: It is important to compare the incidence of bacterial contamination of components collected from the peripheral blood or bone marrow (BM), as well as of components processed with or without cell selection or depletion, and to evaluate the sequelae of such contamination.

Study Design and Methods: Bacterial contamination rates were compared in 1380 untreated autologous peripheral blood progenitor cells (PBPCs), 291 untreated autologous BM samples, 916 monoclonal antibody (MoAb)‐treated autologous and allogeneic BM samples, and in 45 autologous PBPC components from which the CD34+ cells were selected. Bacterial cultures were performed at sequential time points during the processing of MoAb‐treated BM.

Results: Bacterial contamination was documented in 44 of 2632 components from 1593 patients (1.67% of components, 2.76% of patients) before cryopreservation. Although only 0.65% of untreated PBPCs were contaminated before cryopreservation, each patient was more likely to have given a contaminated PBPC component than a contaminated BM component (2.41% vs. 0%, p < 0.01). Bacterial contamination of MoAb‐treated BM was greater during or after manipulation than it was before (2.33% vs. 0.77%, p < 0.05). At thawing, contamination was documented in 42 (1.97%) of 2136 components cultured. Ten (13.7%) of 73 patients who received hematopoietic progenitor cells that were contaminated before cryopreservation or at thawing developed fever or positive blood cultures within 48 hours of transfusion. Fever was associated with bacteremia in two cases, but no irreversible clinical sequelae were noted.

Conclusion: These studies suggest that, despite careful attention to sterile procedures, low‐level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary.
Intraoperative bleeding: a mathematical model for minimizing hemoglobin loss
Authors: Smetannikov Y. , Hopkins D.
Published: March 2003

Background: The rationale for intraoperative blood transfusion is often based on incorrect concepts and criteria.

Study Design and Methods: A mathematical model based on physiologic measures and describing the usual pattern of surgical blood loss is presented, and a theoretical means of minimizing intraoperative hemoglobin loss with hypervolemic hemodilution is proposed.

Results: Intraoperative hemoglobin loss is often overestimated especially in connection with high‐volume blood loss. The model of intraoperative hypervolemic hemodilution shows significant improvement in hemoglobin concentration in the immediate postoperative period, compared with normovolemic conditions. The difference is most marked at a high volume of blood loss and a high degree of maintained hypervolemia.

Conclusion: The practice of intraoperative blood transfusion according to volume of blood lost is to be discouraged, and regular monitoring of the hematocrit is necessary to avoid unnecessary transfusion. The theoretical advantages of hypervolemic hemodilution warrant further testing of the model in a clinical setting.
An EDTA‐associated anti‐B agglutinin: the role of ionized calcium
Authors: Yasuda H. , Ohto H. , Motoki R. , Uchikawa M.
Published: March 2003

BACKGROUND: It is believed that EDTA‐dependent panagglutination is associated with free carboxylic acids that support reactions of rare autoagglutinins. CASE REPORT: An ABO typing discrepancy occurred in an 88‐year‐old patient. The specificity of his autoagglutinin was demonstrated by panel cell study and absorption tests using normal donors' red cells or immunoadsorbents coated with A, B, or O substances. Inhibition assays were performed to determine whether the autoagglutinin was inhibited by ionized calcium or carboxylic acids. The autoagglutinin had anti‐B specificity when tested in the presence of EDTA. It was neutralized by group B secretor saliva and adsorbed by crystalline silica coated with simple B substances with or without EDTA, although it was absorbed by group B red cells only in the presence of EDTA. The agglutinating activity was stronger at 25 degrees C (titer 64) than at 37 degrees C (titer 16) and was destroyed by treatment of the serum with dithiothreitol, which suggests that the autoagglutinin is IgM. This activity also appeared in the patient's serum after dialysis and in an eluate obtained after adsorption with simple B substances, and it was inhibited by the addition of CaCl2 at 0.5 mM or higher concentrations. This suggests that the agglutination is not dependent on EDTA but, rather, on the concentration of ionized calcium. The autoagglutinin failed to react with group B red cells treated with glutaraldehyde for 10 minutes. CONCLUSION: An anti‐B autoagglutinin was shown to have caused an ABO typing discrepancy in the presence of EDTA. These results suggest that autoagglutination requires an environment with low levels of ionized calcium, but not the presence of carboxyl groups.
Impact of various red cell concentrate preparation methods on the efficiency of prestorage white cell filtration and on red cells during storage for 42 days
Authors: Muller‐Steinhardt M. , Janetzko K. , Kandler R. , Flament J. , Kirchner H. , Kluter H.
Published: March 2003

BACKGROUND: White cell (WBC) reduction prior to storage of red cell (RBC) concentrates may reduce the incidence of HLA alloimmunization and may improve the quality of stored RBCs. STUDY DESIGN AND METHODS: An integrated WBC‐reduction filter system was tested after various RBC preparation procedures (from whole blood), and the influence of filtration on RBCs during storage for 42 days was investigated. Four additive system RBC preparation protocols were used. Units prepared from conventional triple blood bags were held for 4 to 6 hours at 22 degrees C, and then the RBCs were separated via a hard spin and filtration, performed immediately (Group 1) or after 18 hours' storage at 4 degrees C (Group 2). Units prepared from a top‐and‐bottom collection system were held at 22 degrees C for 4 to 6 or 22 to 24 hours; the centrifuged RBCs were filtered immediately after preparation (Groups 3 and 4, respectively, by holding time). WBC reduction and filtration time were analyzed. The impact of WBC filtration on pH, hemolysis rate, hemoglobin content, ATP, potassium glucose, and lactate was investigated weekly during storage for 42 days. RESULTS: Filtration reduced the mean WBC count by 3 to 4 log10, to 0.19 +/− 0.25 × 10(6), regardless of the RBC preparation method. Mean filtration times differed significantly between the groups and were longest for Group 1. Besides hemolysis and pH values, which were greater in all filtered units, no major differences were found in filtered and unfiltered RBCs during the storage interval. CONCLUSION: The efficiency of prestorage WBC filtration of RBCs was unaffected by the preparation procedure. However, the filtration time for RBCs freshly prepared in the conventional triple blood bag system without buffy‐coat depletion was unacceptable. No major metabolic differences between filtered and unfiltered RBCs during 42 days of storage were found.
Adherence to a strict specimen‐labeling policy decreases the incidence of erroneous blood grouping of blood bank specimens
Authors: Lumadue J.A. , Boyd J.S. , Ness P.M.
Published: March 2003

BACKGROUND: To assess the effectiveness of a system of preventing incompatible blood transfusions resulting from the misidentification of patient specimens, a prospective analysis of all blood samples submitted to a laboratory was performed. STUDY DESIGN AND METHODS: Incorrectly labeled specimens (rejected samples) were tested for ABO and Rh type, and routine antibody screens were performed. Test results were compared to historic patient data or patient data obtained from subsequently submitted (correctly) labeled specimens. For comparison, all discrepant serologic results from appropriately labeled samples were also recorded. RESULTS: Specimens that failed to meet the criteria for specimen acceptance were 40 times more likely to have a blood grouping discrepancy. CONCLUSION: Strict adherence to the labeling requirements results in a significant decrease in erroneous blood grouping. This would accordingly diminish the likelihood of transfusing out‐of‐group blood components.
Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study
Authors: Houbiers J.G. , van de Velde C.J. , van de Watering L.M. , Hermans J. , Schreuder S. , Bijnen A.B. , Pahlplatz P. , Schattenkerk M. Eeftinck , Wobbes T. , Vries J.E. , Klementschitsch P. , van de Maas A.H. , Brand A.
Published: March 2003

BACKGROUND: Several studies suggest that perioperative blood transfusion is a major independent risk factor for postoperative bacterial infections. Transfusion‐induced immunosuppression is thought to mediate this effect. STUDY DESIGN AND METHODS: In a randomized clinical trial comprising 697 patients with colorectal cancer, the relationship between two types of red cell components (buffy coat‐ depleted packed red cells and white cell‐reduced [filtered] packed red cells) and postoperative bacterial infections was analyzed. RESULTS: Both types of red cells appeared to be associated with a greater incidence of postoperative infection than was no transfusion (39 vs. 24%, p < 0.01). A dose‐response relationship could be demonstrated: the corrected relative risk was 1.6 for 1 to 3 units of red cells and 3.6 for more than 3 units. Multivariate analyses identified the transfusion of red cells and tumor location as the only significant independent risk factors for postoperative bacterial infection. CONCLUSION: Because allogeneic white cells, plasma, microaggregates, citrate, and platelets could be ruled out as risk factors for transfusion‐associated postoperative infections, it is hypothesized that the transfusion of red cells is a potentially detrimental factor that transiently impairs the clearance of bacteria by phagocytic cells.
Importance of ionized magnesium measurement for monitoring of citrate‐ anticoagulated plateletpheresis
Authors: Mercan D. , Bastin G. , Lambermont M. , Dupont E.
Published: March 2003

BACKGROUND: The infusion of citrate during apheresis may affect the levels of ionized magnesium in the blood. Hypomagnesemia and concomitant hypocalcemia could influence the parathormone response and could be responsible for some of the symptoms observed during apheresis. STUDY DESIGN AND METHODS: The study reports measurement of ionized magnesium by the new ion‐selective electrode technique in response to citrate infusion in 15 donors undergoing continuous flow high‐yield plateletpheresis. The monitoring included measurement of ionized calcium and parathormone every 30 minutes during the 120‐minute apheresis (plus the next 30 minutes to assess recovery). RESULTS: Ionized magnesium fell by 30 +/− 4 percent (mean +/− SD, p<0.01), which contrasts with minor changes in total concentrations. Comparison of variations in the levels of ionized and total magnesium found major formation of complexes during citrate infusion. Ionized calcium fell by 15 +/− 3 percent (p<0.01), while parathormone peaked at 356 +/− 114 percent (p<0.01) of initial value after 30 minutes. Ionized cations and parathormone recovered by more than 50 percent within 30 minutes of the end of apheresis. CONCLUSION: An acute and steep drop in ionized magnesium occurs during citrate administration. The measurement of ionized magnesium should be included in future prospective studies of donor safety and parathormone regulation during apheresis.
Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100°C heat after lyophilization
Authors: Santagostino E. , Mannucci P.M. , Gringeri A. , Azzi A. , Morfini M. , Musso R. , Santoro R. , Schiavoni M.
Published: March 2003

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100°C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non‐lipid‐enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods.

STUDY DESIGN AND METHODS: Twenty‐ six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12‐month follow‐up period by the use of serologic and virologic markers for lipid‐ and non‐lipid‐enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period.

RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate.

CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.
Effectiveness of a prospective physician self‐audit transfusion‐ monitoring system
Authors: Lam Hwai‐Tai C. , Schweitzer Stuart O. , Petz Lawrence , Kanter Michael H. , Bernstein David A. , Brauer Stanley , Pascual Delio V. , Myhre Byron A. , Shulman Ira A. , Sun Guo‐Wen
Published: March 2003

BACKGROUND: The purpose of this study was to search for a more effective transfusion‐monitoring system than the existing system of retrospective peer review. STUDY DESIGN AND METHODS: This research used a study‐control, preintervention and postintervention design, to evaluate the effectiveness of a prospective physician self‐audit transfusion‐monitoring system that functioned without the direct involvement of transfusion service physicians. This research also evaluated the effectiveness of issuing to physicians a memo with transfusion guidelines. Three process indicators were used to assess physician behavior at various stages of the blood‐ordering process: 1) the number of crossmatches ordered per admission, 2) the transfusion‐to‐ crossmatch ratio, and 3) the number of blood units returned to the laboratory after physician self‐auditing. The study used two outcome indicators to reflect overall blood utilization: 1) the percentage of patients who received red cell transfusions and 2) the number of blood units transfused per recipient each month. RESULTS: The prospective physician self‐audit system implemented at the study hospital did not reverse physician transfusion decisions, and the process of issuing to physicians a memo with transfusion guidelines at the control hospital failed to reduce blood usage. However, a transient reduction in blood utilization was observed at the study hospital. CONCLUSION: The reduction was hypothesized to be due to a Hawthorne effect, in which observed behavior is affected by the subject's awareness of the research study.