bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiologic background and long‐term course of disease in human immunodeficiency virus type 1‐infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group
Authors: BUSCH M.P. , OPERSKALSKI E.A. , MOSLEY J.W. , STEVENS C.E. , SCHIFF E.R. , KLEINMAN S.H. , LEE H. , LEE M. , HARRIS M. ,   THE TRANSFUSION SAFETY STUDY GROUP
Published: March 2003

BACKGROUND: The long‐term course of human immunodeficiency virus type 1 (HIV‐1)‐related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV‐1‐ infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti‐HIV‐1‐positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6‐month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti‐HIV‐1 screening disproportionately were first‐time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen‐positive at donation. Over a 3‐year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first‐time donations and exclusively homosexual men among seropositive donors suggest that test‐seeking may have contributed to the high HIV‐1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high‐ risk donations. The disease course in HIV‐1‐infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts
The incidence and significance of anti‐“Mia” in Taiwan
Authors: Broadberry R.E. , Lin M.
Published: March 2003

Background: The incidence of the Mill phenotype among Chinese blood donors in Taiwan is 7.3 percent. Anti‐“Mia” is the most frequently occurring alloantibody of potential clinical significance encountered among Chinese patients in Taiwan, with a frequency of 0.28 percent.

Case Reports: A case of hemolytic disease of the newborn and a transfusion reaction due to anti‐“Mia” are described.

Conclusion: It may be important to include the Mill phenotype in the antibody screening of sera from Chinese patients.
Detection of human immunodeficiency virus type 1 p24 antigen and plasma RNA: relevance to indeterminate serologic tests
Authors: Henrard D.R. , Phillips J. , Windsor I. , Fortenberry D. , Korte L. , Fang C. , Williams A.E.
Published: March 2003

BACKGROUND: Most enzyme immunoassay‐reactive specimens producing indeterminate Western blot results belong to individuals who are not infected with human immunodeficiency virus type 1 (HIV‐1). However, a small percentage may correspond to early seroconversion or advanced disease, at which stage partial reactivity on Western blot may be observed.

STUDY DESIGN AND METHODS: To determine the utility of HIV‐1 p24 antigen and cell‐free RNA detection for the resolution of Western blot‐indeterminate serologic results, several types of enzyme immunoassay‐positive, sero‐indeterminate specimens were analyzed. Samples were obtained from infected individuals at the time of seroconversion (n = 20), from patients with AIDS (n = 2), as specimens from clinical samples obtained for diagnostic testing (n = 57), from blood donors producing persistent indeterminate results (n = 47), and from random blood donors (n = 72).

RESULTS: HIV‐1 p24 antigen was detected in 10 of 20 specimens collected from 9 of 12 individuals who seroconverted and in 2 of 2 AIDS patients. HIV‐1 plasma RNA was positive in 22 of 22 samples from those 14 individuals. All of 57 diagnostic specimens and 47 samples obtained from persistently indeterminate donors were negative for HIV‐1 p24 antigen and plasma HIV‐ 1 RNA. One of 72 blood donor specimens was positive for HIV‐1 plasma RNA and had borderline reactivity for p24 antigen.

CONCLUSION: The detection of plasma RNA appears to be sensitive and specific; negative test results may be used to identify false‐positive serologic reactions. The detection of p24 antigen and plasma RNA can also be used to confirm HIV‐1 infection in persons with indeterminate serologic results associated with early seroconversion or late‐stage disease.
Changing blood use in the AIDS era: the case of elective hip surgery
Authors: Atlas S.J. , Singer D.E. , Skates S.J.
Published: March 2003

BACKGROUND: Concern about the transmission of human immunodeficiency virus via blood has substantially increased the public's anxiety about the safety of the blood supply and has encouraged practices to minimize risks deriving from transfusions.

STUDY DESIGN AND METHODS: To assess changes in transfusion practices in elective surgery as awareness of transfusion‐transmitted human immunodeficiency virus emerged, 80 randomly selected patients per year undergoing elective total hip replacement in five calendar years between 1977 and 1989 at a large university teaching hospital were studied.

RESULTS: Total blood use decreased significantly from an average of 3.3 units per patient in 1977 to 2.1 units per patient in 1989 (p = 0.0003). Autologous blood use increased from essentially zero in 1977 to 82 percent of total blood use in 1989 (p < 0.0001). The threshold hematocrit for postoperative transfusion of allogeneic blood (defined by use of logistic regression models) decreased from 30.1 percent (0.30) in 1977 to 26.7 percent (0.27) in 1989 (p = 0.01). As a result of these changes, the proportion of patients exposed to allogeneic blood decreased from 90 to 16 percent across the study period (p < 0.0001). The dramatic decrease in the use of allogeneic blood in elective total hip replacement surgery during the study period was due to decreased demand for blood during and after the operation and to a striking shift in the blood supply from allogeneic to autologous sources.

CONCLUSION: These findings demonstrate that physicians can appropriately alter practices when there are perceived health risks.
JMH variants: serologic, clinical, and biochemical analyses in two cases
Authors: Mudad R. , Rao N. , Issitt P.D. , Roy R.B. , Combs M.R. , Telen M.J.
Published: March 2003

BACKGROUND: JMH is a high‐frequency red cell blood group antigen that resides on a 76‐ to 80‐kDa glycosylphosphatidylinositol‐linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH‐variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH‐variant antigen and produced alloanti‐JMH.

STUDY DESIGN AND METHODS: Murine monoclonal antibodies and human antibodies to JMH were used in hemagglutination, radioimmunoassay, and Western blot testing of red cells from two JMH‐ variant patients; antiserum from one of these patients was also used in biochemical studies. In addition, in vivo survival of JMH‐positive red cells was studied in the same patient.

RESULTS: Biochemically, both examples of red cells with the JMH‐variant phenotype expressed a JMH protein with a molecular weight similar to that of the normal JMH protein. For both patients, family studies suggested an autosomal recessive pattern of inheritance. Survival study demonstrated reduced in vivo red cell survival in one patient.

CONCLUSION: JMH‐variant phenotypes express a protein of normal molecular weight and are inherited in an autosomal recessive pattern. Furthermore, individuals with this phenotype can produce clinically significant antibodies.
Hepatitis C virus infection in hypogammaglobulinemic patients receiving long‐term replacement therapy with intravenous immunoglobulin
Authors: Taliani G. , Guerra E. , Rosso R. , Badolato M. C. , Luzi G. , Sacco G. , Lecce R. , De Bac C. , Aiuti F.
Published: March 2003

BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: A prevalence study was conducted to evaluate the rate of HCV infection in patients undergoing long‐term treatment with IVIG. Fifty‐four patients with congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and biochemical examination. The type of IVIG preparation (type 1 only, type 2 only, or other products) administered to each patient was recorded. Antibodies to HCV were measured by enzyme‐linked immunosorbent assay and immunoblotting; HCV RNA was detected by nested polymerase chain reaction. RESULTS: Anti‐HCV was detected in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom were anti‐HCV‐positive. Abnormal alanine aminotransferase (ALT) levels were found in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p = 0.01) correlated significantly with anti‐ HCV positivity. Moreover, the rates of anti‐HCV positivity and of ALT elevation were significantly higher among patients treated with type 1 IVIG and other products than among those receiving type 2 IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti‐HCV positivity and viremia were frequently observed. The significant correlation between the detection of HCV RNA, the elevation of ALT, and positivity for anti‐ HCV suggests HCV infection. Exclusion of anti‐HCV‐positive donors and of anti‐HCV‐positive IVIG lots should improve the safety of IVIG.
Hepatitis B surface antigenemia in blood donors following vaccination
Authors: Kloster Bruce E. , Kramer Robert E. , Eastlund D. Ted , Grossman Brenda J. , Zarvan Barbara S.
Published: March 2003

BACKGROUND: Detection of hepatitis B surface antigen (HBsAg) in recently vaccinated adults has not previously been reported. Transient detectable HBsAg has been observed in newborn infants immunized with a recombinant hepatitis B vaccine. STUDY DESIGN AND METHODS: Over a 1‐ year period, eight HBsAg‐positive blood donors mentioned during donor notification that they had been vaccinated for hepatitis B virus 1 to 3 days before donation. Follow‐up tests for HBsAg, antibodies to HBsAg, and antibodies to hepatitis B core antigen were performed 3 to 37 weeks after immunization. Four months later, a group of 19 donors who were coworkers received hepatitis B vaccination and then donated blood the next day. The coworkers were observed for duration of antigenemia. RESULTS: A total of nine cases of transient, confirmed (neutralizable) antigenemia occurred in healthy individuals who donated blood 1 to 3 days following vaccination with a recombinant hepatitis B vaccine. Follow‐up testing showed no evidence of infection by hepatitis B virus. One (5.3%) of 19 blood donors vaccinated as a group had antigenemia at Day 1 but not on Days 2 and 3 following immunization. CONCLUSION: Individuals recently vaccinated for hepatitis B may test positive for HBsAg and become permanently disqualified as blood donors. Therefore, blood collection centers should consider temporary deferral of potential donors who recently received hepatitis B vaccine.
Determination of neutrophil antigen gene frequencies in five ethnic groups by polymerase chain reaction with sequence‐specific primers
Authors: Hessner M.J. , Curtis B.R. , Endean D.J. , Aster R.H.
Published: March 2003

Background: The granulocyte antigens NA1 and NA2 are the two recognized allelic forms of Fcγ receptor IIIB. These antigens are clinically relevant, because they are the most frequent targets of neutrophil antibodies in alloimmune neonatal neutropenia, transfusion‐related acute lung injury, and chronic benign autoimmune neutropenia of infancy.

Study Design and Methods: A genotyping assay for NA1 and NA2 using polymerase chain reaction with sequence‐specific forward and reverse oligonucleotide primers has been developed and validated. Genomic DNA was isolated from the peripheral blood of 478 unrelated individuals of five ethnic groups and used as template for NA genotyping.

Results: A validation study of 22 serologically typed samples (2 NA1/NA1, 10 NA1/NA2, and 10 NA2/NA2) was performed. A concordance rate of 100 percent (22/22 samples) was observed between the genotyping assay and serologic typing. In the genotyping study conducted, the NA1 and NA2 gene frequencies observed were 0.31 and 0.69 for African Americans, 0.30 and 0.70 for Asian Indians, 0.37 and 0.63 for whites, 0.53 and 0.47 for Hispanics, and 0.55 and 0.45 for Native Americans, respectively.

Conclusion: Polymerase chain reaction with sequence‐specific primers provides a simple and rapid alternative to neutrophil antigen typing by serologic tests. The NA1 and NA2 gene frequencies observed in Asian Indians and African American populations are similar to those observed in white populations, while those observed in Native American and Hispanic populations are more similar to those previously reported for Asian populations.
Frequency of human immunodeficiency virus (HIV) infection among contemporary anti‐HIV‐1 and anti‐HIV‐½ supplemental test‐ indeterminate blood donors
Authors: Busch M. P. , Kleinman S. H. , Williams A. E. , Smith J. W. , Ownby H. E. , Laycock M. E. , Lee L. L. L. , Pau C.‐P. , Schreiber G. B. ,   The Retrovirus Epidemiology Donor Study
Published: March 2003

Background: Follow‐up studies from the mid‐1980s showed that 1 to 5 percent of blood donors testing reactive in anti‐human immunodeficiency virus type 1 (HIV‐1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV‐1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti‐HIV‐1/HIV type 2 (HIV‐2) EIA‐ reactive, Western blot‐indeterminate donors.

Study Design and Methods: Donations (n = 607) with indeterminate HIV supplemental test results were identified by screening 3,021,342 donations given from November 1990 through August 1993 at five participating blood centers. Consenting donors were enrolled and samples taken 4 to 8 weeks after donation. Follow‐up sera were tested by EIA and Western blot for anti‐ HIV‐1 seroconversion and by type‐specific peptide assays for antibodies to HIV‐2 and HIV‐1 subtype O. Peripheral blood mononuclear cells and/or plasma from the follow‐up samples were tested for HIV‐1 DNA and/or RNA by polymerase chain reaction. The rate of HIV‐1 infection among Western blot‐indeterminate donors was also estimated by multiplying the incidence rate of HIV‐1 seroconversion in this donor population by the estimated duration of the EIA‐reactive and Western blot‐indeterminate window during seroconversion (8.5 days).

Results: Supplemental test‐ indeterminate donors (n = 355) enrolled a median of 38 days after donation; 265 (75%) of these donors were identified as indeterminate after an anti‐HIV‐1/2 EIA‐reactive donation. Enrolled and non‐enrolled donors had similar distributions of demographic characteristics and band patterns. Follow‐up samples from all 355 donors tested negative for HIV‐1 in polymerase chain reaction. Follow‐up sera tested Western blot‐negative in 54 cases (15%) and Western blot‐indeterminate in 299 (84%). Two follow‐up sera (0.6%) were interpreted, according to manufacturer's package insert criteria, as Western blot positive with p24 and gp41 bands and/or gp120/160 bands; however, paired testing of index and follow‐up sera from these two cases showed identical Western blot and EIA reactivity, and polymerase chain reaction was negative for HIV RNA and DNA, which ruled out HIV infection. The absence of HIV infection in 355 Western blot‐indeterminate donors was consistent with our incidence‐based model analysis, which yielded an estimate of one HIV‐1 infection for every 215 Western blot‐indeterminate donations (95% CI, 1/39‐1/8333).

Conclusion: Contemporary blood donors classified as indeterminate in supplemental HIV testing are infrequently infected with HIV. Donors whose follow‐up samples test negative in anti‐HIV‐1/2 EIAs and negative or persistently indeterminate in Western blots should be considered eligible for reinstatement.
Transfusion and cytomegalovirus‐associated AIDS‐defining disease in hemophiliacs. Hemophilia Malignancy Study
Authors: Ragni M. V. , Triulzi D. J. , Bass D. , Duerstein S. ,   THE HEMOPHILIA MALIGNANCY STUDY
Published: March 2003

BACKGROUND: Whether transfusion increases the risk of AIDS‐defining cytomegalovirus (CMV) infection (CMV AIDS) in immunosuppressed patients is not known. Because of concerns about the risk of transfusion transmission of CMV and potential exposure to multiple strains of CMV through transfusion, the National Hemophilia Foundation recently recommended that CMV‐negative blood be used in human immunodeficiency virus‐positive hemophiliacs, regardless of their CMV serologic status. Although the multiple strains of CMV cause different CMV disease manifestations in transplant recipients, there are no data on CMV disease in human immunodeficiency virus‐positive hemophiliacs. STUDY DESIGN AND METHODS: It was hypothesized that if the transmission of CMV through transfusion causes CMV disease in human immunodeficiency virus‐ positive hemophiliacs, then hemophiliacs with CMV AIDS would be more likely to have received transfusions than those with AIDS‐defining disease not caused by CMV (non‐CMV AIDS). The number and type of transfusions were evaluated in 334 hemophiliacs with AIDS (35 with CMV AIDS and 299 with non‐CMV AIDS) enrolled in the multicenter Hemophilia Malignancy Study. RESULTS: There were no differences between hemophiliacs with CMV AIDS and those with non‐CMV AIDS in age, type, and severity of hemophilia; the proportion receiving transfusions; or the mean number of units transfused. These findings persisted after correction for transfusion practice, (i.e., CMV‐unscreened blood vs. CMV‐negative and/or white cell‐reduced blood). There was no difference between the groups in CMV lgG titers or in the proportion who were CMV seropositive, and there was no difference between these parameters in those who had received transfusion(s) and those who had not. CONCLUSION: Transfusion appears to have little, if any, effect on the development of CMV AIDS or CMV lgG seroprevalence in patients with hemophilia.
Molecular background of VS and weak C expression in blacks
Authors: Faas B.H.W. , Beckers E.A.M. , Wildoer P. , Ligthart P.C. , Overbeeke M.A.M. , Zondervan H.A. , von dem Borne A.E.G.Kr. , van der Schoot C.E.
Published: March 2003

BACKGROUND: The Rh system is complex and consists of as many as 45 different antigens. Red cells of about 25 percent of the black population carry VS an Rh‐system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression of e, and usually also of C.

STUDY DESIGN AND METHODS: The RH genes of 11 black VS‐positive donors were studied. Transcripts were sequenced for four VS‐positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried out.

RESULTS: The occurrence of VS was shown to be related to a single‐point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS‐positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D‐CE‐D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression.

CONCLUSION: It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expression of C and VS positivity that is frequently found in blacks.
Mathematical considerations in the practice of acute normovolemic hemodilution
Authors: Kick O. , Daniel E.
Published: March 2003

BACKGROUND: Acute normovolemic hemodilution (ANH) is recommended as a simple and cost‐effective method of autologous transfusion. The present mathematical model, based on the current clinical practice of removing 2 to 3 units of fresh whole blood, defines the indications for ANH. STUDY DESIGN AND METHODS: A mathematical model and subsequent nomograms were developed to define patients for whom removal of 2 to 3 units (450 mL each) would allow a theoretical red cell savings equivalent to 1 unit of packed red cells (volume, 250 mL; hematocrit, 60%), that is, a successful application of the technique. Minimal safe target hematocrits were defined as 30, 26, and 22 percent. RESULTS: The minimal initial hematocrits required for given patient weights are displayed on nomograms derived from the mathematical model. The nomograms also indicate the surgical blood loss allowed without ANH: for example, a 75‐kg man, (2‐unit ANH, minimal safe hematocrit 22%) requires a minimal initial hematocrit of 42 percent (surgical blood loss of 0.64 × estimated blood volume = 3100 mL). CONCLUSION: ANH involving the removal of 2 to 3 units (450 mL each) may be useful in patients with anticipated blood loss exceeding 50 percent of estimated blood volume, high initial hematocrit, and a capacity to tolerate dilution‐induced anemia.
Crossmatch‐compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets
Authors: Gelb A.B. , Leavitt A.D.
Published: March 2003

BACKGROUND: HLA‐matched platelets and crossmatch‐compatible platelets are used to support thrombocytopenic patients who are refractory to randomly selected platelets. Data supporting the effectiveness of crossmatch‐compatible platelets are limited, being essentially restricted to the subset of refractory patients previously shown to be alloimmunized. The authors' hospital does not test for alloimmunization. To determine the effectiveness of crossmatch‐ compatible platelets in an unselected group of refractory patients, the use of such platelets for all patients who are refractory to random‐ donor platelets was reviewed. STUDY DESIGN AND METHODS: All patients who received crossmatch‐compatible platelets between January 1991 and May 1994 were retrospectively reviewed. All study patients were refractory to random‐donor platelets, having two consecutive corrected count increments (CCIs) of < 10,000. A solid‐phase red cell adherence method was used for platelet crossmatching, and CCI was used to monitor the effectiveness of each platelet transfusion. RESULTS: A total of 475 crossmatch‐compatible platelet components were administered to 66 evaluable patients who were refractory to random‐donor platelets. A significant improvement was found in the mean CCI when crossmatch‐ compatible platelets were compared with randomly selected platelets (p < 0.0001): an increase of 8000 +/− 6100 (mean +/− SD). In 59 percent (39/ 66) of the patients, the mean CCI improved to at least 7,500 and in 41 percent (27/66) to at least 10,000. If the 10 patients for whom crossmatch‐compatible platelets were not identified are included, the mean CCI in 51 percent (37/76) of the refractory patients improved to at least 7,500; in 36 percent (27/76), it improved to at least 10,000. The effectiveness of crossmatch‐compatible platelets did not decline with continued use. CONCLUSION: Crossmatch‐compatible platelet components significantly improve the mean CCI for approximately one‐ half of patients who are refractory to random‐donor platelets, even when the patients are not preselected for having alloimmunization to explain their refractory state.
Mini‐pool screening by nucleic acid testing for hepatitis B virus, hepatitis C virus, and HIV: preliminary results
Authors: Cardoso M. S. , Koerner K. , Kubanek B.
Published: March 2003

BACKGROUND: The purpose of this study was to evaluate the feasibility of nucleic acid testing (NAT) of mini‐pools as a blood donation screening test.

STUDY DESIGN AND METHODS: The stepwise implementation of NAT of mini‐pools began in January 1997. Since March 1997, all blood donations collected by the German Red Cross Blood Transfusion Service of Baden‐Wurttemberg were tested for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV nucleic acids. An extra barcoded serum sample is collected from each blood donor for NAT‐based screening, which is performed only on hepatitis B surface antigen‐, anti‐HCV‐, anti‐HIV‐, and anti‐Treponema pallidum‐seronegative donations. Samples are pooled to a maximum of 96. Positive results are resolved through intersecting subpools (a chessboard design). NAT‐based screening does not include a virus concentration step before nucleic acid extraction.

RESULTS: By the end of October 1997, 331, 783 donations in 3,779 pools had been screened. As yet, no viremic but seronegative blood donor has been found for the three markers.

CONCLUSION: It is feasible to incorporate NAT‐based screening of mini‐pools into the routine virus diagnostics of a large blood transfusion service. It remains to be determined whether screening blood donations by NAT will indeed increase the safety of blood supply.
Risk factors for HIV seropositivity among first‐time blood donors in Zimbabwe
Authors: McFarland W. , Mvere D. , Shamu R. , Katzenstein D.
Published: March 2003

BACKGROUND: Factors associated with an increased likelihood of HIV infection among newly recruited blood donors in Zimbabwe are identified. Their feasibility as criteria for exclusion from donation is assessed. STUDY DESIGN AND METHODS: A self‐administered survey including demographic and behavioral questions was completed by 1199 first‐time, volunteer blood donors in Harare, Zimbabwe. Methods for subject recruitment and laboratory screening followed usual blood bank protocols. RESULTS: Fifteen percent of subjects were HIV positive. Factors significantly associated with HIV seropositivity at the p<0.05 level included recruitment venue, age, marital status, donor residence, residence of primary partner, occupation, history of sexually transmitted disease, and condom use. An exclusion strategy based on donor age, condom use, recruitment venue, sexually transmitted disease history, and residence of primary partner would exclude a large proportion of HIV‐infected donors without substantial loss of uninfected donors. CONCLUSIONS: Exclusion of donors who are likely to be infected with HIV is a sound policy for improving blood safety and reducing operating costs worldwide. Identification of efficient donor selection criteria requires knowledge of the local epidemiology of HIV infection and the asking of questions that are likely to be answered accurately.
Granulocyte collection efficiency and yield are enhanced by the use of a higher interface offset during apheresis of donors given granulocyte‐ colony‐stimulating factor
Authors: Adkins D. , Ali S. , Despotis G. , Dynis M. , Goodnough L. T.
Published: March 2003

BACKGROUND: Trials evaluating granulocyte transfusions for therapy of febrile neutropenia demonstrated mixed clinical results, which may in part be due to the low neutrophil cell dose of the transfused components. To optimize the latter variable, the effect of various interface offset (IO) settings during apheresis on granulocyte collection efficiency (GCE) and yield was determined in normal donors given granulocyte‐colony‐stimulating factor (G‐CSF).

STUDY DESIGN AND METHODS: Seventeen donors underwent 44 granulocyte collections performed with a continuous‐flow blood cell separator with hetastarch infusion after stimulation with G‐CSF (5 μ/kg/day). Apheresis was performed alternatively using one of three IO settings: IO = 15 (Group 1, n = 16), IO = 25 (Group 2, n = 12), and IO = 35 (Group 3, n = 13). The GCE and yield and changes in donor platelet count, hematocrit (Hct), and red cell (RBC) volume of the components were compared among the three groups.

RESULTS: The mean GCE was greater (p = 0.006) during apheresis at an IO setting of 35 (60 ± 12%) than at an IO setting of 15 (40 ± 17%). The mean granulocyte yield (×1010 per procedure was 10.8 ± 2.95 at an IO setting of 35 and 7.73 ± 4.02 at an IO setting of 15 (p = 0.08). In a multivariate linear regression model, factors independently associated with granulocyte yield were the absolute granulocyte count (r = 0.73, p < 0.001) and blood volume of the donor (r = 0.54, p = 0.001) before the procedure and the use of an IO setting of 35 (r = 0.50, p = 0.002). There was no significant difference among the three groups in the decrement in donor platelet count or Hct with apheresis, although the mean RBC volume was greater in Group 3.

CONCLUSION: Granulocyte apheresis at an IO setting of 35 rather than 15 resulted in a significant increase in the GCE. The use of an IO setting of 35 during apheresis was an independent factor associated with granulocyte yield in the multivariate model. Donor safety was not compromised by collecting granulocytes at the higher IO setting.
Hepatitis A virus infections associated with clotting factor concentrate in the United States
Authors: Soucie J. M. , Robertson B. H. , Bell B. P. , McCaustland K. A. , Evatt B. L.
Published: March 2003

BACKGROUND: Two cases of hepatitis A among persons exposed to the same lot of solvent/detergent‐treated antihemophilic factor VIII concentrate were reported to a surveillance system. An investigation was conducted to find additional cases and determine the source of infection.

STUDY DESIGN AND METHODS: A seroprevalence study was conducted among persons with exposure to the suspect lot for serologic evidence of recent infection with hepatitis A virus (HAV).

RESULTS: Six cases of recent HAV infection were discovered: four of the patients had been infused with material from the suspect lot of factor VIII, and two had received infusions of factor IX concentrate made from plasma pools common to the suspect factor VIII lot. HAV was identified in one of the plasma pools, in the factor VIII product, and in serum or stool from two factor VIII recipients and one factor IX recipient. The genetics sequence of the virus in the plasma pool, the factor VIII lot, and the factor VIII recipients were identical, while that of the virus in the factor IX recipient differed by a single base.

CONCLUSION: These data document the transmission of HAV by a factor VIII concentrate and implicate factor IX products manufactured from a common source‐plasma pool.
Evaluation and comparison of three mobilization methods for the collection of granulocytes
Authors: Jendiroba D.B. , Lichtiger B. , Anaissie E. , Reddy K. , O'Brien S. , Kantarjian H. , Freireich EJ.
Published: March 2003

BACKGROUND: Cancer chemotherapeutic regimens have become more potent and myeloablative. As a consequence, morbidity and mortality due to opportunistic infections have become a major challenge. The provision of adequate doses of viable granulocytes has thus become an important approach for circumventing the problem. A schedule for collecting therapeutic numbers of cells with minimal donor toxicity has yet to be established.

STUDY DESIGN AND METHODS:An investigation of three mobilization schedules for the collection of granulocytes for transfusion‐granulocyte‐colony‐stimulating factor (G‐CSF) 5 micrograms per kg daily; G‐CSF 5 micrograms per kg every other day, and prednisone 60 mg given orally (20 mg doses at 17 hours, 12 hours, and 2 hours before the collection).

RESULTS:A total of 464 apheresis procedures involving 163 healthy donors were analyzed. Prednisone caused a small increase in the white cell (WBC) counts over the collection days, while G‐CSF every other day and daily schedules improved WBC counts to 145 and 160 percent, respectively (p = 0.004). Similarly, administration of G‐CSF daily and every other day mobilized higher yields of granulocytes over the collection days, compared to the prednisone schedule (170% and 180% vs. 105%; p = 0.02). CONCLUSION: Compared with prednisone, higher WBC yields were achieved by G‐CSF stimulation; G‐CSF given every other day is as effective as daily G‐CSF administration for the recruitment of granulocytes, which makes the mobilization procedure more cost‐ effective.
Evaluation of the Amicus Separator in the collection of apheresis platelets
Authors: Yockey C. , Murphy S. , Eggers L. , Garratty G. , Dingle A. , Helms C. , Moroff G.
Published: March 2003

BACKGROUND: A new apheresis instrument, the Amicus Separator with software versions 2.13 and 2.34, was evaluated for component yields, collection efficiency, and incidence of donor and transfusion recipient reactions. The Amicus was also compared to the Spectra Leukocyte Reduction System (LRS) with version 5 software.

STUDY DESIGN AND METHODS: Single and double apheresis platelets (APs) were collected at two locations. The targeted platelet yields were 4.0 × 10(11) for single APs and 6.8 × 10(11) for double APs. One location used a double‐ needle procedure, and the other used a single‐needle procedure. Along with 28 of the Amicus procedures (14 at each of two locations), the same donors underwent single or double AP collections on the Spectra LRS. APs were tested for platelet yields and residual white cells. APs were transfused in three hospitals. Donor and transfusion recipient reactions and technical problems were documented.

RESULTS: The Amicus Separator efficiently collected single APs (n = 59) and double APs (n = 62) with mean platelet yields of 4.2 × 10(11) and 6.5 × 10(11), respectively. When inlet line alarms occurred in single‐needle procedures, platelet yields were lower and collection times were longer. All APs were white cell‐reduced below 5.0 × 10(6), and all but one AP were white cell‐reduced below 1.0 × 10(6) without filtration. Component yields from the paired Amicus and Spectra LRS procedures were comparable. Collection times (excluding reinfusion/rinseback) were 20 to 23 minutes faster on the Amicus Separator. No serious donor or transfusion recipient reactions occurred.

CONCLUSION: The Amicus Separator provided satisfactory platelet yields and collection efficiency, with shorter collection times than did the Spectra LRS, and it white cell‐reduced components without filtration.
Allogeneic blood progenitor cell collection in normal donors after mobilization with filgrastim: the M.D. Anderson Cancer Center experience
Authors: Anderlini P. , Donato M. , Chan K.‐W. , Huh Y.O. , Gee A.P. , Lauppe M.J. , Champlin R.E. , Körbling M.
Published: March 2003

BACKGROUND: Information on the safety and efficacy of allogeneic peripheral blood progenitor cell (PBPC) collection in filgrastim‐mobilized normal donors is still limited.

STUDY DESIGN AND METHODS: The PBPC donor database from a 42‐month period (12/94‐5/98) was reviewed for apheresis and clinical data related to PBPC donation. Normal PBPC donors received filgrastim (6 μg/kg subcutaneously every 12 hours) for 3 to 4 days and subsequently underwent daily leukapheresis. The target collection was ≥4 × 106 CD34+ cells per kg of recipient's body weight.

RESULTS: A total of 350 donors were found to be evaluable. Their median age was 41 years (range, 4‐79). Their median preapheresis white cell count was 42.8 × 109 per L (range, 18.3‐91.6). Of these donors, 17 (5%) had inadequate peripheral venous access. Leukapheresis could not be completed because of apheresis‐related adverse events in 2 donors (0.5%). Of the 324 donors evaluable for apheresis yield data, 221 (68%) reached the collection target with one leukapheresis. The median CD34+ cell dose collected (first leukapheresis) was 462 × 106 (range, 29‐1463). The main adverse events related to filgrastim administration in donors evaluable for toxicity (n = 341) were bone pain (84%), headache (54%), fatigue (31%), and nausea (13%). These events were rated as moderate to severe (grade 2‐3) by 171 (50%) of the donors. In 2 donors (0.5%), they prompted the discontinuation of filgrastim administration.

CONCLUSION: PBPC apheresis for allogeneic transplantation is safe and well tolerated. It allows the collection of an “acceptable” PBPC dose in most normal donors with one leukapheresis, with minimal need for invasive procedures.
Corrected count increment and percent platelet recovery as measures of posttransfusion platelet response: problems and a solution
Authors: Davis K.B. , Slichter S.J. , Corash L.
Published: March 2003

BACKGROUND: Corrected count increment (CCI) and percent platelet recovery (PPR) are measures of response to platelet transfusion that “correct” the count increment for blood volume and number of platelets transfused. Their potential for data distortion is described, and a regression analysis is suggested that is more informative and avoids the inherent problems associated with using ratios as outcome measures.

STUDY DESIGN AND METHODS: Data from the first platelet transfusion for 585 patients from the Trial to Reduce Alloimmunization to Platelets (TRAP) were used to model methods of analyzing posttransfusion platelet response.

RESULTS: By linear regression analysis, unfiltered platelet components gave a greater posttransfusion increment on average (p = 0.001), but filtered platelets gave a greater increment per platelet transfused (p = 0.003). In contrast, CCI and PPR showed no difference between filtered and unfiltered platelets (p = 0.36 and p = 0.29, respectively) because they combined the effects of dose, filtration, and patient size. Slightly fewer patients are required for a study analyzed by regression analysis.

CONCLUSION: Regression analysis of posttransfusion platelet increments should be used instead of CCI or PPR to compare the efficacy of platelet components. CCI and PPR should not be used to define platelet refractoriness as a study outcome, because these measures are biased in favor of platelet preparation techniques that provide fewer platelets.
Platelet membrane integrity during storage and activation
Authors: Reid T.J. , Esteban G. , Clear M. , Gorogias M.
Published: March 2003

BACKGROUND: The platelet cell membrane appears to undergo a lipid‐phase transition on cooling from 23°C to 4°C. Consequences of this phase transition are leakage of cellular material and irreversible cellular damage. Whether agents, of known benefit in protecting membranes and proteins from cooling and drying injury, could also protect platelets was investigated. Leakage of cytosolic components was assessed by measuring the release of fluorescein into the surrounding medium.

STUDY DESIGN AND METHODS: Fresh platelets were suspended in 5 percent dimethyl sulfoxide (DMSO) or in 5 mM of one the following agents: glucose, trehalose, sucrose, glycerol, ethylene glycol, 1,2‐propanediol, or l‐proline. Platelets were loaded with 10 nM fluorescein diacetate (FD), chilled at 4°C for 24 hours or frozen at –1°C per minute to –70°C, warmed rapidly at 37°C, and centrifuged, and the supernatant was measured for the presence of fluorescein. The effect of FD on platelets was assessed by agglutination with ristocetin, aggregation with thrombin and ADP, platelet‐induced clot retraction, and expression of p‐selectin. Platelet function and activation before and after freezing or cooling were measured by the same methods.

RESULTS: By flow cytometry, 98 percent of the platelets incorporated FD. The trapped fluorescein resulted in neither platelet activation (p = 0.9) nor reduction of platelet function (p = 0.12‐0.94) from that in control platelets. Freezing of platelets in DMSO caused far less release of fluorescein than did freezing with other agents (p<0.001) or chilling of platelets at 4°C for 24 hours (p<0.0001). Supernatant levels of fluorescein correlated inversely with platelet function. Fluorescein was also shown to be released during aggregation with thrombin or ADP but not during agglutination with ristocetin.

CONCLUSIONS: Release of fluorescein into the surrounding medium indicated a loss of platelet membrane integrity and function. Cellular loading with FD is a simple method of studying membrane integrity of platelets and other cells.
Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair
Authors: Carson J.L. , Altman D.G. , Duff A. , Noveck H. , Weinstein M.P. , Sonnenberg F.A. , Hudson J.I. , Provenzano G.
Published: March 2003

BACKGROUND: The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare.

STUDY DESIGN AND METHODS: A retrospective cohort study of 9598 consecutive hip fracture patients at least 60 years old who underwent surgical repair was performed. The primary outcome was serious bacterial infection, defined as bacteremia, pneumonia, deep wound infection, or septic arthritis or osteomyelitis. Secondary outcomes included two individual infections, pneumonia and urinary tract infection (UTI), and the cost of infection. Hospital cost of infection was assessed by linking the study population to Medicare data.

RESULTS: Fifty‐eight percent of patients received at least one transfusion. Serious bacterial infection occurred in 437 patients (4.6%); 28.8 percent of this group died during the hospital stay. Pneumonia occurred in 361 patients (3.8%) and UTI occurred in 1157 patients (12.1%). The adjusted risk of serious bacterial infection associated with transfusion was 1.35 (95% CI, 1.10‐1.66). The adjusted risk for pneumonia was 1.52 (95% CI, 1.21‐1.91), and that for UTI was 1.03 (95% CI, 0.91‐1.17). A dose‐response relationship was present for serious bacterial infection (p = 0.001) and pneumonia (p = 0.001). The cost of hospitalization was $14,000 greater for patients with serious infection than for patients without infection.

CONCLUSION: Blood transfusion is associated with a 35‐percent greater risk of serious bacterial infection and a 52‐percent greater risk of pneumonia. Postoperative infections are costly. The risk of bacterial infection may be the most common life‐threatening adverse effect of allogeneic blood transfusion.
Comparison of the performance of four microtube column agglutination systems in the detection of red cell alloantibodies
Authors: Weisbach V. , Ziener A. , Zimmermann R. , Glaser A. , Zingsem J. , Eckstein R.
Published: March 2003

BACKGROUND: The purpose of this study was to compare the performance of four currently available microtube column agglutination systems in the detection of red cell alloantibodies to that of the standard tube low‐ionic‐strength solution (LISS) indirect antiglobulin test (IAT) (tube LISS‐IAT).

STUDY DESIGN AND METHODS: In a comparative study, 172 sera, previously demonstrated to contain red cell alloantibodies, were tested in parallel by the tube LISS‐IAT and three microtube column agglutination techniques (DiaMed‐ID, Ortho BioVue, and Sanofi‐Pasteur Scangel) and one affinity‐adherence test system (Gamma ReACT). Tests were performed simultaneously by a single person on freshly thawed sera that had been frozen at ‐20°C.

RESULTS: The rate of detection of clinically significant alloantibodies (n = 154) in microtube column systems was very similar. One hundred forty‐one sera (91.6%) reacted in the DiaMed‐ID, 139 (90.3%) in the ReACT, 139 (90.3%) in the BioVue, and 142 (92.2%) in the Scangel. Only 117 (76.0%) of these sera reacted in the tube LISS‐IAT. The detection rates for 18 antibodies of minor clinical significance (anti‐M, ‐N, ‐P1, ‐Lea, and ‐Leb) varied among the test systems: DiaMed‐ID, 5 (28%); ReACT, 7 (39%); BioVue, 14 (78%); Scangel, 10 (56%); and tube LISS‐IAT, 6 (33%). Antibody reactivity as determined by titer and score was very similar in all microtube column systems and higher in these systems than in the tube LISS‐IAT.

CONCLUSION: The sensitivity of all four microtube column systems in the detection of clinically significant red cell alloantibodies was similar and was markedly superior to that of the tube LISS‐IAT. An individual cost‐benefit analysis should be performed in every institution to decide whether a microtube column system should be applied. If so, the antibody screen in the microtube column agglutination system should ideally be performed in advance of the crossmatch to provide time to screen for compatible units.
Prevalence of GB virus type C/hepatitis G virus RNA and anti‐E2 among blood donors in Southeastern France
Authors: Cantaloube Jean‐François , Gallian Pierre , Biagini Philippe , Attoui Houssam , Escher Jacqueline , Zappitelli Jean‐Pierre , Delord Yves , De Micco Philippe , De Lamballerie Xavier
Published: March 2003

BACKGROUND: The purpose of the study was to analyze serologic and molecular markers of the GB virus type C/hepatitis G virus (GBV‐C/HGV) infection in voluntary blood donors from Southeastern France.

STUDY DESIGN AND METHODS: Sera were tested for the presence of GBV‐C/HGV RNA by reverse transcriptase‐polymerase chain reaction and that of antibodies to the GBV‐C/HGV E2 (anti‐E2) antigen by an enzyme‐linked immunosorbent assay. A first cohort (1660 blood donors) was tested prospectively and a second cohort (238 samples with hepatitis markers) was tested retrospectively. Donors in the prospective study were questioned for possible risk factors of virus transmission. Amplification products were sequenced and subjected to phylogenetic analysis.

RESULTS: Approximately 2.6 percent of individuals accepted for blood donation and 15.4 percent with positive hepatitis C virus serologic tests carried GBV‐C/HGV RNA. Anti‐E2 was detected in these two populations in approximately 12 percent and 48 percent of donors, respectively. Moderate relative risks were found only in tattooed or pierced individuals (1.82) and health care workers (2.45). Almost all strains were located in the same phylogenetic branch as HGV Group 2.

CONCLUSION: Though a large proportion of the donors tested have been in contact with GBV‐C/HGV, no elevated relative risk of infection was identified. The phylogenetic distribution of viral strains suggests that the infection is endemic in this population.
Ceftizoxime‐induced hemolysis due to immune complexes: case report and determination of the epitope responsible for immune complex‐mediated hemolysis
Authors: Endoh Teruo , Yagihashi Atsuhito , Sasaki Masateru , Watanabe Naoki
Published: March 2003

BACKGROUND: Several occurrences of immune complex‐mediated, cephalosporin‐induced intravascular hemolysis have been reported. This report describes the first case of hemolytic anemia caused by an immune‐complex mechanism associated with ceftizoxime and delineates the epitope responsible for hemolysis.

CASE REPORT: The patient's serum was tested for antibody that reacted with five penicillins and 30 cephems (all types of cephalosporins) by using protocols to detect drug‐adsorption and immune‐complex mechanisms. The patient's antibody that formed immune complexes with ceftizoxime reacted with 10 of 30 cephems. These 10 drugs were classified as oxime‐type cephalosporins, which have a common structural formula consisting of [(Z)‐2‐(2‐amino‐4‐thiazolyl)‐2‐methoxyiminoacetoamido] at the C7 position on 7‐aminocephalosporinic acid with or without substitution at the C3 position.

CONCLUSION: The patient's antibody recognized a common structure in 10 oxime‐type cephalosporins, and immune complexes formed by the antibody specifically or nonspecifically bound to red cell membranes. Therefore, when intermittent antibiotic therapy is required, as in this case, care should be taken in antibiotic selection to avoid drug‐induced hemolytic anemia. In addition, when this type of hemolysis is observed, tests for antibody that reacts by adsorption and immune‐complex mechanisms should be performed against penicillins and cephems to select antibiotics not showing a cross‐reaction.