bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous resolution of transfusion‐associated graft‐versus‐host disease
Authors: Mori S. , Matsushita H. , Ozaki K. , Ishida A. , Tokuhira M. , Nakajima H. , Kizaki M. , Sugiura H. , Kikuchi A. , Handa M. , Kawai Y. , Yamamori S. , Ikeda Y.
Published: March 2003

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a serious complication of blood transfusion that is characterized by high fever, a scaly maculopapular erythematous rash, diarrhea, hepatocellular damage with marked elevation of liver function test values, and pancytopenia. It can occur in immunocompetent as well as immunocompromised recipients. The existence of atypical TA‐GVHD that resolves spontaneously and does not exhibit all of the manifestations has been suggested, but there has been to date no documented diagnosis of GVHD supported by evidence of engraftment.

CASE REPORT: A female patient presented and was diagnosed with acute myelogenous leukemia (AML:M4), and, after unsuccessful combination chemotherapy, she received a transfusion and developed manifestation of TA‐GVHD as well as evidence of chimerism. TA‐GVHD was proved by demonstrating Y chromosome‐specific genes in the skin by polymerase chain reaction. The manifestations of clinical GVHD abated within 4 months.

CONCLUSION: Polymerase chain reaction analysis of Y chromosomes in specimens from female patients is useful in the diagnosis of suspected cases of spontaneously resolving TA‐GVHD.
Prevalence of antibodies to human T‐lymphotropic virus types I and II in volunteer blood donors and high‐risk groups in northwestern Greece
Authors: Dalekos George N. , Zervou Eleftheria K. , Karabini Fotini K. , Elisaf Moses S. , Bourantas Kostantinos L. , Siamopoulos KC
Published: March 2003

BACKGROUND: In addition to human immunodeficiency virus, human T‐ lymphotropic virus types I and II (HTLV‐I/II) is prevalent among blood donors in the United States. In Greece, there are no epidemiologic data regarding the prevalence of HTLV‐I/II among volunteer blood donors and high‐risk groups. STUDY DESIGN AND METHODS: To determine the prevalence of HTLV‐I/II infections in northwestern Greece, a seroepidemiologic study was conducted among volunteer blood donors, multiply transfused patients, heroin addicts, and chronic hemodialysis patients. The subjects were tested for serologic evidence of HTLV‐I/II infection by enzyme immunoassays and specific protein immunoblot confirmatory test. RESULTS: None of the volunteer blood donors and heroin addicts had detectable antibodies to HTLV‐I/II. Only 1 (1.45%) of the 69 multiply transfused patients had indeterminate results, while 2 (1.2%) of 163 hemodialysis patients were positive. CONCLUSION: In northwestern Greece, routine screening for HTLV‐I and HTLV‐II infections does not appear to be required. However, the finding of seropositivity among hemodialysis patients requires further evaluation of the origin of the infection, as its zero prevalence in this population seems to exclude transfusion transmission.
How much would the safety of blood transfusion be improved by including p24 antigen in the battery of tests?
Authors: le Pont F. , Costagliola D. , Rouzioux C. , Valleron A. J.
Published: March 2003

BACKGROUND: Because p24 antigen may be detectable during seroconversion, before antibodies, some of the infected blood undetected by antibody screening could be identified through antigen screening.

STUDY DESIGN AND METHODS: The potential benefit of antigen screening was evaluated in a simulation model incorporating present knowledge of the time sequence from antigen exposure to antibody development during seroconversion and the incidence of seroconversion among repeat donors. The model was designed so that the results were consistent with the observed rate of antibody‐positive blood donations and the CIs of surveys that did not find any antibody‐negative/antigen‐ positive donated blood.

RESULTS: In the United States in 1990, the number of expected, undetected, contaminated blood components was estimated at 68; of these 8 to 17 could have been identified by antigen screening, depending on the hypothesis explored. (In 1992, 20 undetected, contaminated blood components were expected according to this model, of which 2 to 5 could have been identified by antigen screening.) In France, the comparable figures were 1 to 4 of 13 in 1990 and 1 to 2 of 7 in 1992.

CONCLUSION: The projected benefit must be weighted against possible negative consequences, including 1) an increase in recently infected persons seeking p24 antigen screening at blood banks (assuming this test is not incorporated into screening in non‐blood bank settings) and 2) the need for additional quality assurance procedures to avoid operational flaws associated with the increase in the donor screening test battery. In any case, the best way of increasing the safety of blood is improvement in the selection of donors, which can diminish the residual risk of transmission of any viruses.
Transfusion of donor‐type red cells as a single preparative treatment for bone marrow transplants with major ABO incompatibility
Authors: Nussbaumer W. , Schwaighofer H. , Gratwohl A. , Kilga S. , Schönitzer D. , Nachbaur D. , Niederwieser D.
Published: March 2003

BACKGROUND: Major ABO incompatibility of a bone marrow donor and recipient entails the risk of severe hemolytic transfusion reactions.

STUDY DESIGN AND METHODS: Nineteen patients who received transplants of bone marrow from donors whose ABO type was a major mismatch with the recipients were treated with plasma exchanges transfusion (n = 7) or donor‐type red cell transfusion (n = 12) to remove isoagglutinins from the recipient. Efficacy, side effects, engraftment, and transfusion requirements were analyzed for the two treatment groups.

RESULTS: Both treatment methods were well tolerated, were of comparable efficacy in removing ABO antibodies, and did not affect the engraftment of platelets, red cells, or white cells. Except for observations in one patient, whose renal function was already impaired before red cell treatment and who developed reversible renal failure after transplant, no significant differences in serum creatinine levels were observed in the two groups after treatment. Only serum levels of lactate dehydrogenase measured, as a sign of hemolysis, on Day 0 (488 +/− 110 vs. 191 +/− 30 U/L in the red cell and plasma exchange groups, respectively, p < 0.05) were higher in the red cell group than in the plasma exchange group.

CONCLUSION: Transfusion of donor‐type red cells is an effective means of preventing hemolytic reactions in patients who receive marrow transplants from donors whose ABO type is a major mismatch. It is technically simple and well tolerated, even in patients with high‐titer isoagglutinins, but it should be avoided in patients with abnormal renal function.
Serum hepatitis C virus (HCV) RNA: a reliable tool for evaluating HCV‐ related liver disease in anti‐HCV‐positive blood donors with persistently normal alanine aminotransferase values
Authors: Nalpas B. , Romeo R. , Pol S. , Thiers V. , Carnot F. , Berthelot P. , Brechot C.
Published: March 2003

BACKGROUND: The significance of hepatitis C virus (HCV) antibodies in blood donors with persistently normal alanine aminotransferase (ALT) levels requires evaluation.

STUDY DESIGN AND METHODS: The serum and the liver were assayed for HCV RNA. Liver histology was analyzed in 14 HCV‐ positive subjects who had repeatedly normal ALT values over a follow‐up period of at least 3 months.

RESULTS: HCV RNA was not detected in liver and serum, and liver histology showed minimal changes in more than one‐ half of the subjects (8/14), even if third‐generation recombinant immunoblot assay was positive; this demonstrated that HCV can be eradicated spontaneously. Moderately histopathological liver lesions were usually found in HCV RNA‐positive subjects (6/14), but one subject had active disease that required interferon therapy; this shows that chronic hepatitis may be present in HCV‐positive individuals despite repeatedly normal transaminase values. HCV genotypes other than 1b (II) were usually identified, and the presence or absence of serum and liver HCV RNA correlated completely in all 14 patients.

CONCLUSION: Serum HCV RNA should be assayed in those HCV‐positive donors having repeatedly normal transaminase activity; if it is positive, indicating an ongoing HCV infection, a liver biopsy should be performed to measure the degree of the liver disease and determine the appropriate antiviral therapy.
Red cell compatibility testing in baboon xenotransplantation
Authors: Triulzi D.J. , Jochum E.E.
Published: March 2003

BACKGROUND: Although baboon ABO group and human anti‐baboon heteroagglutinin (HA) titers have been considered in the selection of baboon donors for clinical hepatic xenotransplantation, the biologic role of these antibodies is not yet known. However, because of the potential importance of ABO hemagglutinins, a method for baboon ABO group determination is described, as are the titers of HA observed in both baboons and normal human donors.

STUDY DESIGN AND METHODS: The ABO group of 62 baboons was determined by modified reverse typing. Baboon sera were heated and absorbed with human group O red cells. Reverse typing was then performed by standard techniques. HA titers at room temperature (RT) and in the antiglobulin test (AGT) were assessed in 10 baboons by using human red cells and in 33 normal donors by using baboon red cells.

RESULTS: Ten (16%) baboons were group A, 29 (47%) were group B, 23 (37%) were group AB, and none were group O. In tests using human group O red cells, HA titers in 10 baboons ranged from 1 to 32 at RT and from negative to 64 in the AGT. All 33 normal human sera contained anti‐baboon HA. Under a hemagglutination scoring system, group A persons had the lowest HA scores (17 +/− 15 at RT, 31 +/− 19 in the AGT), and group B persons had the highest HA scores (67 +/− 4 at RT, 85 +/− 9 in the AGT).

CONCLUSION: Baboon ABO group can be easily determined by modified reverse serum typing. Both baboons and humans possess HAs of variable titer. Among humans, titers appear to be highest in group B individuals and lowest in group A. Additional studies are needed to determine the clinical significance of these antibodies.
False‐positive hepatitis B surface antigen screening test results in patients receiving granulocyte‐colony‐stimulating factor
Authors: Mair D. C. , Brecher M. E. , Hom E. , Owen H. G. , Shea T. C.
Published: March 2003

BACKGROUND: Granulocyte‐colony‐stimulating factor (G‐CSF) is used for the mobilization of progenitor cells and granulocytes. False‐positive hepatitis B surface antigen (HBsAg) enzyme‐linked immunosorbent assays (ELISAs) (NML) from one manufacturer in individuals receiving G‐CSF have been observed. STUDY DESIGN AND METHODS: Sixty‐six autologous peripheral blood progenitor cell donors from 1994 were retrospectively reviewed. Donors typically received 5 to 10 micrograms of G‐CSF per kg subcutaneously for 5 days before collection. Additional ELISA dilutional studies (1‐in‐10, 1‐in‐100, 1‐in‐1000) with known HBsAg‐ negative serum were made with G‐CSF. Testing was performed by the University of North Carolina, the American Red Cross in Charlotte, NC, or the National American Red Cross, Washington, DC. RESULTS: Of the 66 patients, none reacted for antibody to hepatitis B core antigen, and 30 (45%) had a positive reaction in the ELISA. Surface antigen positivity was “confirmed” on 6 of the 30 patients by neutralizing ELISA reactivity with an antibody to HBsAg test from the same manufacturer. In all cases, the clinical presentation was not suggestive of hepatitis, and these individuals were not at high risk for hepatitis B. Twenty‐seven of the 30 cases were tested with a monoclonal HBsAg ELISA (AUSZYME) from another manufacturer in the peridonation period and did not react. In 1994, 256 autologous whole‐blood donors not receiving G‐ CSF were similarly tested and only 1 (0.4%) had a positive reaction with the second manufacturer's HBsAg ELISA (p < 0.001). Of this group, 41 patients with histories of malignancy were identified, which is comparable to the history of the peripheral blood progenitor cell donors in this study, and none of these blood donors tested positive for HBsAg (p < 0.001). Dilutional studies with G‐CSF produced no reactions. CONCLUSION: The NML HBsAg ELISA studied has an unacceptably high false‐positive rate in patients or donors receiving G‐CSF. The false reactivity of this assay appears to be an indirect consequence of G‐CSF administration, which can also lead to spurious confirmation by the HBsAg neutralization assay from the same manufacturer.
Interviews of individuals diagnosed as anti‐human immunodeficiency virus‐positive through the screening of blood donations in the Paris area to 1994: reflections on the selection of blood donors
Authors: Lefrère J.‐J. , Elghouzzi M.‐H. , Salpétrier J. , Duc A. , Dupuy‐Montbrun M.‐C.
Published: March 2003

BACKGROUND: One of the aims of the medical interview routinely preceding each blood donation is the identification of individuals with a risk factor for infection with the human immunodeficiency virus (HIV).

STUDY DESIGN and METHODS: Interviews were performed with individuals diagnosed as being seropositive for HIV through the systematic biologic screening of blood donations in the Paris area to establish, first, the circumstances allowing HIV‐seropositive individuals to pass through the predonation medical interview and, second, the motivation of these individuals as blood donors. Risk factors of 30 HIV‐infected donors identified between 1991 and 1994 were determined.

RESULTS: When asked whether they recognized the eventual risk to recipients of donated blood, 14 (47%) of 30 answered positively. Fifteen (50%) admitted having given their blood to determine their HIV status.

CONCLUSION: These individuals did not exclude themselves from blood donation and probably hid their risk factor(s) at the predonation interview in order to be accepted as blood donors.
Transfusion patterns in pediatric open heart surgery
Authors: Chambers L. A. , Cohen D. M. , Davis J. T.
Published: March 2003

BACKGROUND: Transfusions in pediatric open heart surgery were analyzed to determine the percentage of patients transfused, the types and volumes of blood components used, and the relationships among transfusions, patient characteristics, surgeon, and surgical procedure.

STUDY DESIGN and METHODS: In a 9‐month period, 122 patients, aged 12 or less (median, 1 year; 31% <4 months old), underwent 126 procedures (37 routine, 60 complex, 29 repeat operations). Bypass circuit size and priming solution, target intraoperative hematocrit, heparinization, protamine reversal, and transfusion indications and doses were standardized. The number of full “adult” units of packed red cells (RBCs), units of fresh‐frozen plasma (FFP), and platelet concentrates (PCs) transfused in the operating room through postoperative Day 3 were tabulated.

RESULTS: RBCs, FFPs, and PCs were transfused in 98, 54, and 58 percent of cases, respectively. Twenty‐two percent of components were transfused postoperatively. The average numbers of components transfused for complex procedures (3.4 RBCs, 6.1 total) and repeat operations (4.0 RBCs, 8.1 total) were greater than those for routine procedures (1.8 RBCs, 2.1 total) (p<0.01). The average total number of components transfused did not correlate with surgeon or patient age; patients <4 months old used the largest mean numbers of RBCs and total components of all types. For four procedures, preoperative crossmatch and directed‐donation collection orders that would be expected to produce acceptable utilization rates and a <15‐percent chance of needing additional components were determined.

CONCLUSION: Blood order protocols for pediatric open heart surgery can be procedure‐specific, should address the use of non‐red cell components, and should cover early postoperative transfusions.
Parvovirus B19 infection in patients with hemophilia
Authors: Ragni M.V. , Koch W.C. , Jordan J.A.
Published: March 2003

Background: The long‐term consequences of parvovirus B19 infection in transfusion recipients are not known, and thus the value of B19 screening of blood donors remains unresolved. Hemophiliacs, at risk for B19 through their chronic exposure to clotting factor concentrates, have frequent, close medical follow‐up and thereby constitute an ideal group in which to study the hematologic sequelae of B19 infection.

Study Design and Methods: An enzyme‐linked immunosorbent assay was used to detect B19 IgG and IgM and the polymerase chain reaction was used to detect B19 DNA in frozen, stored plasma samples, obtained between 1987 and 1994, from 136 subjects with hemophilia, including 71 who were human immunodeficiency virus (HIV)‐positive and 65 who were HIV‐ negative. Then the results of the tests were compared with clinical hematological data and blood product usage data.

Results: B19 seroprevalence in the hemophilic cohort was 81.6 percent (111/136), including 74.6 percent (53/71) of HIV‐positive and 89.2 percent (58/65) of HIV‐negative hemophiliacs. It was not affected by age, type or severity of hemophilia, HIV status, CD4 number, or yearly blood product usage. Only 1 (0.7%) of the 136 samples was positive for B19 IgM and none was positive in polymerase chain reaction for B19 DNA. After adjusting for HIV status, there were no differences between B19‐ positive and B19‐negative hemophiliacs in hematologic values, CD4 counts, or blood product use.

Conclusion: Although B19 IgG seroprevalence in this hemophilic cohort is high and indicative of past B19 infection, there is no detectable B19 viral activity or any associated long‐term clinical or hematologic sequelae.
Sensitivity and specificity of four assays to detect human T− lymphotropic virus type I or type I/II antibodies
Authors: Vrielink H. , Reesink H.W. , Zaaijer H.L. , Poel C.L. van der , Cuypers H.T.M. , Lelie P.N.
Published: March 2003

Background: Assays that detect human T‐lymphotropic virus type I and type II antibody (HTLV‐I/II) are widely used in the routine screening of blood donors.

Study Design and Methods: Four commercially available anti‐HTLV‐I (Fujirebio and Organon Teknika) or ‐HTLV‐I/II assays (Murex and Ortho) were evaluated in various serum panels: A) HTLV‐I‐positive specimens (n = 41), confirmed by Western blot and polymerase chain reaction; B) a commercially available anti‐HTLV‐I/II panel; C) serial dilutions of sera from HTLV‐I‐positive individuals (n = 30), confirmed by immunofluorescence assay and Western blot: D) serial dilutions of HTLV‐II‐positive blood donors (n = 20), confirmed by Western blot and polymerase chain reaction, and E) sera from first‐time blood donors (n = 1055).

Results: All four assays elicited reactions in all 82 HTLV‐I‐ positive samples in Panels A, B, and C. Of 32 HTLV‐II‐positive specimens in Panels B and D, 31 (96.9%) reacted in the Organon Teknika assay and all 32 reacted in the remaining tests. Probit analysis of test results in Panels C and D indicated that the Fujirebio test was the most sensitive assay, followed by Organon Teknika, Ortho, and Murex. The specificities of Fujirebio, Murex, Organon Teknika, and Ortho tests in 1055 first‐time blood donors were 99.9, 100, 99.6, and 99.9 percent, respectively.

Conclusion: All four studied assays for detecting HTLV‐I or HTLV‐I/II antibodies are appropriate as screening tests.
Fatal hemolytic transfusion reaction resulting from ABO mistyping of a patient with acquired B antigen detectable only by some monoclonal anti‐ B reagents
Authors: Garratty G. , Arndt P. , Co A. , Rodberg K. , Furmanski M.
Published: March 2003

Background: Some monoclonal anti‐B reagents are prepared exclusively from an anti‐B clone, ES4, that is known to detect acquired B antigens that are not detectable by other anti‐B clones or polyclonal anti‐B reagents.

Case Report: A 92‐year‐old group A, Rh‐negative man with diverticulitis was mistyped as group AB with the use of a monoclonal anti‐B. The hospital did not detect anti‐B in the patient's serum. After a negative antibody screen, blood was issued through an abbreviated crossmatch (i.e., immediate‐spin crossmatch). The patient was given 3 units of group AB blood and 1 unit of group A blood, and no problems were reported. After the transfusion of a inverted question markfourth unit of AB blood the patient had a severe hemolytic transfusion reaction which resulted in kidney failure and death 10 days later. After the transfusion reaction, the patient's pretransfusion red cells were found to be group A with an acquired B antigen. The monoclonal anti‐B used the hospital was formulated from the ES4 clone. A sample of the patient's serum taken before the transfusion was later found to contain a weak anti‐B, detectable most obviously by the antiglobulin test, which was not performed at the crossmatch stage. The manufacturers of monoclonal anti‐B reagents prepared from ES4 have since modified their reagents (i.e., lowered the pH) so that they now detect only the strongest examples of acquired B antigen.

Conclusion: A fatal hemolytic transfusion reaction resulted because a monoclonal anti‐ B that detected acquired B antigen was used to type red cells from an elderly man whose serum had weak anti‐B that was not detected by abbreviated compatibility testing.
Data on apheresis, blood collection, and transfusion‐related activities: statistical analyses of the American Association of Blood Banks institutional membership questionnaires
Authors: Devine P. , Goldstein R. , Linden J.V. , Postoway N. , Hoffstadter L.K. , Hines D.M.
Published: March 2003

Background: The American Association of Blood Banks annually surveys institutional members on activities pertinent to blood collections, apheresis, and transfusions.

Study Design and Methods: Retrospective descriptive statistics and comparative statistical analyses including trend tests were performed on selected topics from the 1989, 1990, and 1991 Institutional Questionnaires. The data were compiled by institution type, namely, regional and community blood donor collection centers and hospital‐based facilities. Evaluated topics included the apheresis and therapeutic procedures performed, transfusion‐associated AIDS and hepatitis, and the blood components (red cells, platelets, fresh‐frozen plasma, and cryoprecipitate) that were collected, transfused, or outdated or discarded.

Results: Significant findings (p<0.05) included upward trends over time in the numbers of donor plateletpheresis units collected and transfused and in the numbers of random‐donor platelet concentrates collected by hospitals. There was an upward trend over time in the outdating or discarding of all blood component types that was reported by hospitals. Data from blood centers showed the outdating or discarding of significant numbers of apheresis platelets, fresh‐frozen plasma, and cryoprecipitate. No significant trends were identified in the reported cases of transfusion‐associated hepatitis or AIDS.

Conclusion: Ongoing data analysis of the institutional questionnaires provides information on trends in blood collection and transfusion‐related activities.
The red cell chemokine receptor is distinct from the Fy6 epitope
Authors: Hausman E. , Dzik W. , Blanchard D.
Published: March 2003

BACKGROUND. Previous studies established an association between the red cell chemokine receptor and Fy6 of the Duffy glycoprotein. The relationship between Duffy system antigens and interleukin 8 binding by red cells was examined.

STUDY DESIGN AND METHODS. Interleukin 8 adsorption was measured by using red cells from owl, squirrel, and rhesus monkeys, and human red cells before and after saturation with anti‐Fya (anti‐Fy1), anti‐Fyb (anti‐Fy2), or anti‐Fy6. The effect of cell saturation with interleukin 8 on Duffy system antigen expression and the effect of enzyme treatment on interleukin 8 adsorption were also examined. RESULTS. Fy:1,‐2,6 or Fy:‐1,2,6 (owl monkey, squirrel monkey, human) red cells adsorbed interleukin 8 over a wide range of concentrations (125–1000 pg/mL). Human Fy:‐1,‐2,‐6 red cells bound minimal interleukin 8. Human red cells saturated with corresponding antibodies displayed decreased interleukin 8 binding. Saturation of human cells with interleukin 8 failed to interfere with Duffy system antigen expression. Rhesus monkey cells lacking Fy1, Fy2, and Fy6 were able to adsorb interleukin 8 in a manner similar to Fy:1,‐2,6 or Fy:‐ 1,2,6 primate cells. Ficin treatment eliminated both Duffy system antigen expression and interleukin 8 adsorption from red cells.

CONCLUSIONS. The Duffy glycoprotein binds interleukin 8. Although previous studies suggested that interleukin 8 bound either directly to or close to the Fy6 epitope, the ability of Fy:‐1,‐2,‐6 rhesus monkey cells to adsorb interleukin 8 suggests that the interleukin 8 receptor is distinct from Fy6, Fy1, and Fy2.
Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non‐B, non‐C outcomes
Authors: Mosley J.W. , Huang W. , Stram D.O. , Nowicki M.J. , Hollinger F.B. , Aach R.D. , Stevens C.E. , Barbosa L.H. , Nemo G.J.
Published: March 2003

Background: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non‐B, non‐C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti‐HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients.

Study Design and Methods: Data on blood donors and recipients enrolled in the Transfusion‐Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti‐HBc testing of donors and anti‐HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients.

Results: For HCV cases, donor ALT alone (at ≥ 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti‐HBc alone (at ≥ 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected].

Conclusion: The indirect tests proved to be equal in sensitivity to the first‐generation anti‐HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti‐HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.
Studies on platelets exposed to or stored at temperatures below 20°C or above 24°C
Authors: Holme S. , Sawyer S. , Heaton A. , Sweeney J. D.
Published: March 2003

BACKGROUND: Platelet concentrates (PCs) may be subjected to temperatures outside 20 to 22 degrees C during shipping or storage, which may have an adverse effect on platelet quality.

STUDY DESIGN AND METHODS: These studies systematically evaluated the effect of short‐ term exposure (≤ 24 hours) of platelets to temperatures above 22° or below 20° C as part of standard 5‐day PC storage at 22° C, as well as the effect of long‐term storage (5 days) at 24 and 26° C. For the short‐term exposure studies, up to 6 units of Day 1 standard PCs were mixed, split, and returned to the containers. Test units were then stored without agitation in an incubator at a specific temperature (4, 12, 16, or 18° C) for various times up to 24 hours, after which they were stored with agitation at 22° C. One unit acted as control and was stored at 20 to 22° C throughout the 5‐day storage period. Loss of platelet discoid shape was determined photometrically by the extent of shape change assay, by an increase in apparent platelet size by morphologic evaluation, and by swirling.

RESULTS: A gradual loss of platelet discoid shape occurred at temperatures below 20° C. For similar periods, a greater difference between test and control PCs was observed in units held at 4° C than in those held at 16° C. The data were fitted to an equation to relate platelet discoid shape (% of control) to exposure temperature and time. Assuming that a 20‐percent decrease or more in the extent of shape change assay represents a significant loss in platelet viability, the equation predicts that such a loss occurs when the platelets are exposed to 16° C for ≥16 hours, to 12° C for ≥10 hours, or to 4°C for ≥6 hours, whereas exposure to 18° C for ≤24 hours has no significant effect. Storage for 5 days at temperatures ≤26° C was not associated with any significant reduction in platelet discoid shape or other measures of platelet quality.

CONCLUSION: There was a gradual loss of platelet discoid shape at exposure temperatures < 20°C, which worsened as temperatures decreased and exposure times increased to 24 hours. This relationship can be described in an equation that could be used as a guideline for allowable exposure conditions.
Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus‐negative hemophiliacs multiply transfused with a monoclonal antibody‐purified factor VIII concentrate
Authors: Smid W.M. , Martens A. , van der Meer J. , Hegge‐Paping C.S.M. , Halie M.R.
Published: March 2003

BACKGROUND: Serum levels of the soluble interleukin 2 receptor (sIL‐2R) and soluble CD8 (sCD8) may be used as markers of T‐cell activation. The course of serum levels of sIL‐2R and sCD8 in hemophiliacs who were treated first with an intermediate‐purity factor VIII concentrate and then with a monoclonal antibody (MoAb)‐purified factor VIII concentrate are reported.

STUDY DESIGN AND METHODS: Serum samples taken before the administration of the MoAb‐purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus‐negative patients with hemophilia A were analyzed. Eighteen healthy age‐matched men were used as controls.

RESULTS: The sIL‐2R and sCD8 levels were higher in patients treated with intermediate‐purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL‐2R levels showed a decrease after 5 years of treatment with the MoAb‐purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL‐2R tended to increase between 2 and 5 years (p = 0.07). The sIL‐2R and sCD8 levels were not related to the numbers of T‐lymphocytes and HLA‐DR‐positive T‐lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL‐2R levels and CD4‐positive cell numbers or between sCD8 levels and CD8‐positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL‐2R levels are due to the use of the MoAb‐purified concentrate.

CONCLUSION: Elevated levels of sIL‐2R and sCD8 were found in multiply transfused human immunodeficiency virus‐ negative hemophiliacs. After treatment was changed to the use of a MoAb‐ purified concentrate. sIL‐2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.
Limited utility of alanine aminotransferase screening of hepatitis C antibody‐screened blood donors
Authors: Cable R. , Badon S. , Pray C. , Popovsky M.A.
Published: March 2003

BACKGROUND: The introduction of hepatitis C virus (HCV) screening has significantly reduced the frequency of posttransfusion hepatitis C. To examine the current added value of alanine aminotransferase (ALT) screening, all donor screening at two large blood centers was reviewed. STUDY DESIGN AND METHODS: From July 1991 through March 1994, 1,258,000 allogeneic blood donors were screened by enzyme immunoassay for anti‐ HCV: 343,000 donations by the first‐generation test (HCV 1.0) and 915,000 donations by the second‐generation test (HCV 2.0). Donations with positive EIA results were confirmed with a recombinant immunoblot assay. RESULTS: Of these donors, 1,637 (0.13%) were confirmed as HCV‐ positive and 21,666 (1.72%) had elevated ALT. To estimate the additional margin of safety due to ALT screening, all donors who seroconverted were reviewed, and those donors who had elevated ALT but were HCV negative on a previous donation were identified. One hundred eleven HCV seroconversions were observed: 19 seroconversions from HCV 1.0‐negative to HCV 1.0‐confirmed‐positive, 82 apparent seroconversions from HCV 1.0‐negative to HCV 2.0‐confirmed‐positive, and 10 seroconversions from HCV 2.0‐negative to HCV 2.0‐confirmed‐positive. The number of apparent HCV 1.0‐negative to HCV 2.0‐positive seroconversions was much greater than expected, which reflected the increased sensitivity of HCV 2.0. Only 15 donors were identified who had an elevated ALT on a previous HCV‐negative blood donation, and all of these were among those who apparently seroconverted from HCV 1.0‐ negative to HCV 2.0‐confirmed‐positive. Out of the 10 HCV 2.0‐ seroconverting donors, no donor was found who was initially HCV 2.0 negative with elevated ALT and later was HCV 2.0 positive; nor were such donors found among 4 additional HCV 2.0‐seroconverting donors. CONCLUSION: With the introduction of HCV 2.0 screening. ALT appears to have little value as a surrogate test for hepatitis C, and ALT testing was unable to detect any donors who later seroconverted, as detected by HCV 2.0.
Polymorphism of the h allele and the population frequency of sporadic nonfunctional alleles
Authors: Wagner F.F. , Flegel W.A.
Published: March 2003

BACKGROUND: Current polymerase chain reaction‐based strategies for phenotype prediction often fail when sporadic nonfunctional alleles are encountered. The population frequency of such mutations was not known for any gene under low selection pressure and may be best examined in blood group systems lacking prevalent nonfunctional alleles. The frequency of the very rare Bombay blood group (Oh, genotype hh sese) was recently determined in a systematic survey of more than 600,000 white individuals.

STUDY DESIGN AND METHODS: With this survey used in conjunction with additional blood samples, the population frequency of nonfunctional alleles of the gene encoding the α(1,2)fucosyltransferase (H or FUT1) was determined.

RESULTS: Seven different h alleles were found in five unrelated individuals, three of whom were homozygous for unique alleles. There was no prevalent h allele. Five missense and one frameshift mutations were observed, that were the presumptive causes of the null phenotype; the coding sequence of one h allele was identical to the H sequence. The average inbreeding factor α was 0.00116. The frequency of nonfunctional alleles at the H gene locus was calculated as 1 in 347 in a large white population (95% Cl: 1:185–1:824).

CONCLUSION: The Bombay blood group phenotype in white is due to diverse, sporadic, nonfunctional alleles without any prevalent allele. Assuming similar rates of nonfunctional alleles in glycosyltransferase genes like ABO, current genotyping strategies may fail as often as once in about 300 individuals of blood group O. Sporadic neutral alleles may also pose a serious obstacle for population‐wide screening of many disease‐associated genes.
Blood counts in healthy donors 1 year after the collection of granulocyte–colony‐stimulating factor‐mobilized progenitor cells and the results of a second mobilization and collection
Authors: Stroncek D.F. , Clay M.E. , Herr G. , Smith J. , Ilstrup S. , McCullough J.
Published: March 2003

BACKGROUND: Granulocyte–colony‐stimulating factor (G–CSF)‐mobilized blood cells are being used for allogeneic transplants, but the long‐term effects of G–CSF on healthy individuals are not known. Furthermore, it is not certain how many CD34+ cells can be collected in a second mobilization and collection procedure.

STUDY DESIGN AND METHODS: Nineteen people were given 2, 5, 7.5, or 10 μg of G–CSF per kg per day for 5 days, and blood progenitor cells were collected by apheresis on the sixth day; this was done on two occasions separated by at least 12 months. Blood counts obtained before and after each course of G–CSF and the quantity of cells collected were compared.

RESULTS: There were no differences in white cell (WBC), platelet, red cell, and WBC differential counts measured before each course of G–CSF, and all the values were in the normal range. In a subset of 12 people who received 7.5 or 10 μg of G–CSF per kg per day for both courses, the numbers of neutrophils, mononuclear cells, and CD34+ cells in the blood after each course were similar (34.1 ± 7.31 × 109/L vs. 36.4 ± 12.3 × 109/L, p = 0.24; 6.59 ± 2.28 × 109/L vs. 5.63 ± 2.11 × 109/L, p = 0.24; and 92.0 ± 55.6 × 106/L vs. 119.2 ± 104.6 × 108/L; p = 0.48, respectively), as were the quantities of mononuclear cells (31.0 ± 8.4 × 109 vs. 31.0 ± 6.1 × 109; p = 0.64) and CD34+ cells (417 ± 353 × 106 vs. 449 ± 286 × 106; p = 0.53) collected in the two apheresis procedures. Furthermore, there was a positive correlation between the quantity of CD34+ cells collected from each of the 12 people per liter of whole blood processed in the two procedures (r2 = 0.86, p<0.001).

CONCLUSION: One year after the administration of G–CSF to healthy people, their blood counts were normal and unchanged from pretreatment counts. If healthy people donate blood progenitor cells after a second G–CSF course, the quantity of CD34+ cells collected will be similar to that obtained in the first collection.
The COBE Spectra cell separator is more effective than the Haemonetics MCS‐3P cell separator for peripheral blood progenitor cell harvest after mobilization with cyclophosphamide and filgrastim
Authors: Morton J.A.P. , Baker D.P. , Hutchins C.J. , Durrant S.T.S.
Published: March 2003

BACKGROUND: Peripheral blood is rapidly replacing bone marrow as a source of hematopoietic progenitor cells for autologous transplantation. The advantages of peripheral blood progenitor cell transplantation are enhanced by the ability to collect sufficient progenitor cells to ensure rapid neutrophil and platelet recovery in a single procedure on some cell separators. STUDY DESIGN AND METHODS: A prospective randomized study was undertaken to compare peripheral blood progenitor cell yields from two cell separators (MCS‐3P, Haemonetics and Spectra, COBE). Fifteen consecutive patients were mobilized with cyclophosphamide 2 g per m2 (Day 0) and filgrastim 10 micrograms per kg (Days 1–11). Consecutive collections (Day 10, Day 11) were performed with each machine once: patients were randomly assigned to either machine for the initial collection. RESULTS: Collection time was longer on the MCS‐3P (p = 0.001), and the volume processed was greater with the Spectra (p < 0.0001). Despite similar nucleated cell yield (p = 0.62), the yield of CD34+ cells (p = 0.001) and colony‐forming units‐ granulocytic‐monocytic (p = 0.0001) was significantly higher with the Spectra. The yield of nucleated cells per unit of blood volume processed was higher for the MCS‐3P (p = 0.0007), while the CD34+ cell yield (p = 1) and colony‐forming units‐granulocytic‐monocytic yield (p = 1) per unit of blood volume processed were similar for the two machines. The collection of CD34+ cells at levels > 2 × 10(6) per kg (p = 0.063), 5 × 10(6) per kg (p = 0.031), and colony‐forming units‐ granulocytic‐monocytic > 1 × 10(5) per kg (p = 0.25) after a single collection was superior for the Spectra. CONCLUSION: The yield of progenitor cells after collection on the Spectra was superior to that achieved with the MCS‐3P, because of the larger volume of blood processed per procedure. This would permit more patients to undergo only one collection.
Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors
Authors: Herrera Guillermo A. , Lackritz Eve M. , Janssen Robert S. , Raimondi Vincent P. , Dodd Roger Y. , Aberle‐Grasse John , Petersen Lyle R.
Published: March 2003

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T‐ lymphotropic virus via the transfusion of seronegative, infectious window‐period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV‐positive and HIV‐infectious window‐ period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T‐lymphotropic virus). This proportion multiplied by the estimated number of HIV‐infectious window‐ period donations is the number of post‐screening HIV‐infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS‐reactive donations were 12 times more likely to be HIV positive (odds ratio=11.9; 95% CI=5,26). However, of an estimated 13 infectious window‐ period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post‐screening HIV infections and other blood‐borne diseases.
Viral RNA in the resolution of human immunodeficiency virus type 1 diagnostic serology
Authors: Brown A. E. , Jackson B. , Fuller S. A. , Sheffield J. , Cannon M. A. , Lane J. R.
Published: March 2003

BACKGROUND: Assays for human immunodeficiency virus (HIV) antibody testing are characterized by very high levels of sensitivity and specificity. Nonetheless, serologic testing of HIV‐infected individuals before they produce multispecific HIV antibodies will not detect and confirm those individuals as positive for HIV. This study was carried out to determine whether viral RNA in such specimens is detectable in a quantitative RNA polymerase chain reaction assay. STUDY DESIGN AND METHODS: Study specimens were identified through the United States military HIV testing program. Thirty‐five individuals were studied whose HIV type 1 (HIV‐1) infection status was serologically inconclusive at initial testing (i.e., reactive on enzyme immunoassay, nondiagnostic or nonreactive on Western blot), but who were documented to be infected (n = 15) or uninfected (n = 20) through the testing of subsequently collected (follow‐up) sera. HIV‐1 RNA was detected in sera by the use of a commercially available, quantitative, reverse transcriptase‐polymerase chain reaction assay. RESULTS: Specimens from 15 individuals subsequently confirmed to be positive for HIV antibody were all positive for HIV‐1 RNA. Specimens from 19 of 20 individuals subsequently confirmed to be negative for HIV antibody were negative for HIV‐1 RNA. In the one HIV‐1 RNA‐positive serum from this group, the RNA copy number was low; specimen contamination during prior laboratory testing was suspected. CONCLUSION: Viral RNA was detected in specimens collected for serologic diagnosis of HIV infection in which no special precautions had been taken to preserve the nucleic acid. Such molecular methods potentially add a much needed tool to current HIV testing algorithms.
Effects of resuscitation fluids on nonadaptive immune responses
Authors: Sillett H.K. , Whicher J.T. , Trejdosiewicz L.K.
Published: March 2003

BACKGROUND: Colloidal plasma‐expander fluids are commonly used as an alternative to blood components in the resuscitation of patients suffering from hemorrhagic shock and trauma. Of these, hydroxyethyl starch is also used as a cryopreservative, and these dual properties have been utilized in the development of a blood storage system that allows the direct transfusion of red cells. The prolonged intravascular persistence of hydroxyethyl starch suggests that phagocytic clearance may be impaired and that the presence of hydroxyethyl starch could exacerbate transfusion‐induced immunomodulation. STUDY DESIGN AND METHODS: The effects of colloidal resuscitation fluids on the activation response and phagocytic function of polymorphonuclear cells (PMNs) and monocytes in normal peripheral blood were examined. To mimic the hemolysis associated with cryopreservation, the effects of 1‐ and 5‐ percent red cell lysate were studied. Flow cytometric assays were used in all cases. RESULTS: The percentage of phagocytic monocytes and PMNs was not altered; nor were the rates of phagocytosis impaired after incubation with resuscitation fluids. Upregulation of cell surface integrin during activation was similarly unmodified by the fluids. CONCLUSION: Hydroxyethyl starch and other resuscitation fluids do not affect some important antimicrobial functions of the nonadaptive arm of the immune response. This suggests that posttrauma or transfusion‐ induced immunomodulation is not exacerbated by inhibition at this level.
Evaluation of a new automated instrument for pretransfusion testing
Authors: Morelati F. , Revelli N. , Maffei L. M. , Poretti M. , Santoro C. , Parravicini A. , Rebulla P. , Cole R. , Sirchia G.
Published: March 2003

BACKGROUND: A number of automated devices for pretransfusion testing have recently become available. This study evaluated a fully automated device based on column agglutination technology (AutoVue System, Ortho, Raritan, NJ).

STUDY DESIGN AND METHODS: Some 6747 tests including forward and reverse ABO group, Rh type and phenotype, antibody screen, autocontrol, and crossmatch were performed on random samples from 1069 blood donors, 2063 patients, and 98 newborns and cord blood. Also tested were samples from 168 immunized patients and 53 donors expressing weak or variant A and D antigens. Test results and technician times required for their performance were compared with those obtained by standard methods (manual column agglutination technology, slide, semiautomatic handler).

RESULTS: No erroneous conclusions were found in regard to the 5028 ABO group and Rh type or phenotype determinations carried out with the device. The device rejected 1.53 percent of tests for sample inadequacy. Of the remaining 18 tests with discrepant results found with the device and not confirmed with the standard methods, 6 gave such results because of mixed‐field reactions, 10 gave negative results with A2 RBCs in reverse ABO grouping, and 2 gave very weak positive reactions in antibody screening and crossmatching. In the samples from immunized patients, the device missed one weak anti‐K, whereas standard methods missed five weak antibodies. In addition, 48, 34, and 31 of the 53 weak or variant antigens were detected by the device, the slide method, and the semiautomated handler, respectively. Technician time with the standard methods was 1.6 to 7 times higher than that with the device.

CONCLUSION: The technical performance of the device compared favorably with that of standard methods, with a number of advantages, including in particular the saving of technician time. Sample inadequacy was the most common cause of discrepancy, which suggests that standardization of sample collection can further improve the performance of the device.