Prevalence, donation practices, and risk assessment of blood donors with hemochromatosis.

CONTEXT: Despite changes in eligibility policies, practical barriers limit blood donations from individuals with hemochromatosis. Increased knowledge of hemochromatosis donor characteristics may help foster further changes that will promote more donations. OBJECTIVES: To estimate the prevalence of donors diagnosed as having hemochromatosis and to compare rates of unreported deferrable risks for transfusion-transmissible viral infections (TTVIs), positive screening test results for TTVIs, and donation patterns between hemochromatosis patient donors and donors reporting no medical conditions necessitating phlebotomy (non-health-related donors). DESIGN: An anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study. SETTING AND PARTICIPANTS: Among a stratified probability sample of 92 581 blood donors from 8 geographically diverse US blood centers, 52 650 (57%) responded. MAIN OUTCOME MEASURES: Prevalence of hemochromatosis among blood donors; prevalence of unreported deferrable risks and positive screening test results for TTVIs among hemochromatosis patient donors vs non-health-related donors. RESULTS: One hundred ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients and 50 079 (95.1%) as non-health-related donors. An estimated 0.8% of all donations were from hemochromatosis patients, 45.8% of whom reported that they had donated blood to treat their illness. The proportion of repeat donors was higher in hemochromatosis patients than in non-health-related donors (83.5% vs 76.5%; P =.03). Among repeat donors, 68.7% of hemochromatosis patients reported donating at least 3 times in the past year compared with 49.1% of non-health-related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs was similar in hemochromatosis patients (2.0%) and non-health-related donors(3.1%) as was the overall prevalence of positive screening test results (1.3% of hemochromatosis patients vs 1.6% of non-health-related donors). CONCLUSIONS: Although significant numbers of hemochromatosis patients reported donating blood for therapeutic reasons, our findings suggest that this population does not present a greater risk to blood safety than other donors.

Absence of human T-lymphotropic virus type I tax sequences in a population of normal blood donors in the Baltimore, MD/Washington, DC, area: results from a multicenter study.

BACKGROUND: It was reported recently that sequences corresponding to the human T-lymphotropic virus type I (HTLV-I) tax gene were detected in peripheral blood mononuclear cells from 8 to 11 percent of healthy blood donors without detectable antibodies to HTLV-I. A multicenter blind study was conducted to determine if these results could be independently confirmed. STUDY DESIGN AND METHODS: Specimens were collected from 100 anti-HTLV-I-negative healthy blood donors and from 11 anti-HTLV-I- or anti-HTLV-II-positive individuals. All samples were coded and distributed to each of four independent testing laboratories for polymerase chain reaction analysis to detect sequences of the HTLV-I or HTLV-II tax gene, using detailed procedures specified by the laboratory reporting the original observation. Each laboratory also tested a dilution panel of a plasmid containing HTLV-I tax to determine the analytical sensitivity of the procedure. RESULTS: The analytical sensitivity of the screening methods permitted detection of as few as 1 to 10 copies of the tax gene. However, HTLV-I tax sequences could not be detected in any of the anti-HTLV-I-negative blood donors at more than one test site. CONCLUSION: HTLV-I tax sequences appear not to be present in this population of 100 blood donors negative for anti-HTLV-I.

Cord Blood Transplantation Study (COBLT): cord blood bank standard operating procedures.

In 1995, the National Heart Lung and Blood Institute (NHLBI) solicited requests for a proposal (RFP) entitled "Transplant Centers for Clinical Research on Transplantation of Umbilical Cord Stem and Progenitor Cells." Three banks, six transplant centers, and one medical coordinating center (MCC) (Table 1) were funded with the overall goal of banking cord blood units (CBU) using a single manual of operations. Furthermore, the clinical protocols to evaluate the transplant outcome for adult and pediatric recipients of these well-characterized CBU would be analyzed in a uniform fashion. Because of the intense interest of the transplantation community in the policies and procedures for cord blood collection and processing, the principal investigators of the cord blood banks (CBB) and NHLBI elected to submit for publication the rationale and an abridged, but detailed, version of the standard operating procedures (SOP) developed between October 1996 and July 1998 prior to the initiation of the clinical protocols to be performed with these CBU. As the SOP will be refined over time, the complete SOP and subsequent amendments will be published and continually updated on the websites from the MCC-The EMMES Corporation (www.EMMES.com). All forms referred to in this document may be obtained from the EMMES website. It is hoped that the publication of this document will lay down a framework that will not only facilitate the development of other CBB but also help us more rapidly define what constitutes an "acceptable" CBU product.

Hemolysis in sickle cell disease as measured by endogenous carbon monoxide production. A preliminary report.

To detect and quantitate temporal variations of the hemolytic rate in sickle cell disease, the authors measured endogenous carbon monoxide (CO) production in five normal subjects, nine patients with sickle cell anemia (SS) in steady clinical state, and two patients with sickle cell-hemoglobin C (SC) disease in and out of pain crises. The red blood cell life span calculated from these data (RCLSco) ranged from 81.2 to 102.9 days (mean +/- standard deviation [SD] 88.0 +/- 9.2, coefficient of variation [CV] 10.2%) for the normal subjects and 8.0-24.7 days (mean +/- SD 12.1 +/- 5.1, CV 42.1%) for those with SS. Although the individual figures for RCLSco for the normal subjects and those with SS fell within the range previously obtained by radioisotopic techniques for the respective groups, the mean values calculated from the CO technique were slightly (though not significantly) shorter for the normal subjects and about 25% shorter for the subjects with SS (P less than 0.01). Repetitive studies were performed in four subjects with SS who were clinically stable; the temporal variability in the calculated hemolytic rate differed considerably from patient to patient (CV 3.6%, 7.0%, 17.0%, 28.0%). In two patients concurrent RCLS studies were performed by the CO technique and 51Cr tagged red blood cells. In one patient, the RCLS was similar by the two techniques, in the other, a two exponent 51Cr curve did not permit calculation of RCLS. In the two patients with SC disease there was no difference in RCLSco during and after recovery from pain crisis. Although the CO technique may overestimate the turnover of circulating heme mass, especially in the presence of hemolysis, the results of serial studies in a small number of patients with SS suggest but do not prove temporal variations in hemolytic rate in SS.

Thymosin in the early diagnosis and treatment of high risk homosexuals and hemophiliacs with AIDS-like immune dysfunction.

PIP: The adnormal levels of thymosin alpha 1 in acquired immunodeficiency syndrome (AIDS) patients, depressed T-cell function, thymus pathology, and the restoration of T-cell function by thymosin fraction 5 (TF5) lend support to the hypothesis that the thymus plays a central role in AIDS. The thymosin alpha 1 assay may provide a means of identifying symptomatic carriers of AIDS. This paper summarizes the current status of diagnostic studies with thymosin alpha 1 in AIDS and reports the 1st clinical trial with thymosin in subjects with AIDS-like immune dysfunction. Serum samples from intravenous drug abusers, homosexuals, and Haitians with AIDS have revealed thymosin alpha 1 levels at least 2 standard deviations from the mean of controls without AIDS. Preliminary data from a pilot study in homosexuals and hemophiliacs at high risk for AIDS suggest that the administration of TF5 may be effective in reconstituting some T-cell mediated specific immune functions, including cell-medicated lympholysis (CML) and the mixed lymphocyte response (MLR), and enhancing the lectin-induced production of T-cell growth factor. On the other hand, TF5 has failed to have any effects on the T4/T8 ratio, absolute lymphocyte counts, or natural killer cell activity.^ieng

Complications related to equipment and technique.

Automated cytapheresis, when performed by experienced operators using modern equipment, is remarkably free of adverse effects. A declining pattern of equipment failure and related problems has been recorded in the 220,000 procedures performed by the American Red Cross in the past 5 years. Other cytapheresis centers report similar findings. Current CBCS are safe and reliable, and defects in plastic disposables, while irritating, result in little danger to the donor. Operator vigilance and careful attention to the details of the procedure can eliminate the majority of serious potential complications that have been encountered to date.

Chronic lymphocytic leukemia: a monoclonal disease.

A black woman with chronic lymphocytic leukemia (CLL) was found to have monoclonal B lymphocytes with one type of surface immunoglobulin and one variant of G6PD (glucose-6-phosphate dehydrogenase) (G6PD A). Erythrocytes and T cells contained both G6PD A and G6PD B and hence were of polyclonal origin. The CLL cells in this patient likely arose from a developmental stage later than the step of differentiation into T and B lymphocytes. Furthermore, her erythrocytes did not arise from a stem cell affected by the CLL process.

Oat cell carcinoma mimicking leukemia.

A patient with oat cell carcinoma had circulating carcinoma cells, which initially suggested a diagnosis of acute leukemia. The correct diagnosis was made only by histopathologic examination of the bone marrow. A case of a similar bone marrow disorder, which developed after diagnosis of oat cell carcinoma, is also presented.

Screening for abnormal hemoglobins: who, when, and how.

Sickle cell and abnormal hemoglobin screening programs should not be undertaken lightly but rather should have a specific purpose or purposes. If the aim is to detect only sickle hemoglobin, a certain strategy is necessary. If the goal is to detect all abnormal hemoglobins and genetic counseling is planned, another approach should be used. A simple solubility test detects sickle hemoglobin with high reliability, but deals with no other abnormal hemoglobins. Hemoglobin electrophoresis, followed by other tests as indicated, is then necessary to ascertain other abnormal hemoglobins in addition to hemoglobin S.

Cholelithiasis in sickle cell anemia: a case for elective cholecystectomy.

Ten patients with sickle cell anemia over the age of 10 who had cholecystectomy are reported. All had symptomatic cholecystitis; three had biliary tract obstruction. Transfusions were given preoperatively and with attention to oxygenation and fluid and electrolyte balance. There were few complications, none serious. Based upon the frequency of gallstones over the age of 10, the likelihood of symptoms or serious complications and the apparent ease with which the properly prepared sickle cell patient comes through surgery, we recommend routine cholecystograms in all adolescent and adult sickle cell anemia patients with elective cholecystectomy for those who have stones.

Proton nuclear magnetic resonance studies of hemoglobin Providence (beta82EF6 Lys replaced by Asn or Asp): a residue involved in anion binding.

High-resolution proton nuclear magnetic resonance studies of hemoglobins Providence-Asn (beta82EF6 Lys replaced by Asn) and Providence-Asp (beta82EF6 Lys replaced by Asp) show that different amino acid substitutions at the same position in the hemoglobin molecule have different effects on the structure of the protein molecule. Hemoglobin Providence-Asp appears to be in a low-affinity tertiary structure in both the deoxy and carbonmonoxy forms. Deoxyhemoglobin Providence-Asn has its beta heme resonance shifted downfield slightly from its position in normal adult hemoglobin; however, the tertiary structures of the heme pocket of hemoglobins A and Providence-Asn are very similar when both proteins are in the carbonmonoxy form. These results are consistent with the oxygen equilibrium measurements of Bonaventura, J., et al. [(1976) J. Biol. Chem. 251, 7563] which show that both Hb Providence-Asn and Hb Providence-Asp have oxygen affinities lower than normal adult hemoglobin, with Hb Providence-Asp having the lowest. Our studies of the effects of sodium chloride on the hyperfine shifted proton resonances of deoxyhemoglobins A, Providence-Asn, and Providence-Asp indicate that the beta82EF6 lysine is probably one, but not the only binding site for chloride ions.

Delayed hemolytic transfusion reactions. An often-missed entity.

Delayed hemolytic transfusion reactions in eight persons were manifested solely or primarily by an apparently unexplained posttransfusion decrease in the hematocrit value. Alloantibodies were eventually found in all eight patients, but were sometimes undetectable for as long as 72 hours after the reaction. This did not preclude the occurrence of a new, acute hemolytic reaction. There were three instances of reversible renal failure complicating the reaction. In two patients, some or all of the antibodies became undetectable after four and nine months. In a third, the indirect antiglobulin reactions became considerably weaker after 12 months. Patients previously sensitized to RBC antigens should have available records inspected and a warning device (wristband or wallet card) provided to help prevent reactions caused by an anamnestic antibody rise.

Irreversibly sickled cells and red cell survival in sickle cell anemia: a study with both DF32P and 51CR.

For 25 subjects with sickle cell anemia the mean red cell life span measured with Di-isopropylfluorophosphite-32P (DF32P) was 17.32 +/- 4.51 days. Performed simultaneously, the half life (T1/2 of radioactively-labelled chromium 51Cr) was 10.11 +/- 2.82 days (14 subjects). Eight additional subjects, or more than 30 per cent of those studied using both red cell tags, had 51Cr red cell survival curves better described by two exponents than by one, apparently due to two different rates of 51Cr elution from the red cells. This finding limits the value of quantitative data obtained by this procedure. A negative correlation was found between the mean red cell life span measured with DF32P-tagged cells and the proportion of irreversibly sickled cells in venous or capillary blood. A similar negative correlation was found between the red cell half survival time measured with 51Cr-tagged cells and the proportion of irreversibly sickled cells. These data are compatible with the view that repeated sickling and, in particular, the formation of irreversibly sickled cells play a distinct role in the pathogenesis of hemolysis in sickle cell anemia.

The in vivo survival of red blood cells stored in modified CPD with adenine: report of a multi-institutional cooperative effort.

In order to provide data in support of licensure applications for citrate-phosphate-dextrose (CPD) supplemented with adenine, a multi-institutional cooperative effort was organized to determine survivability of red blood cells subjected to prolonged liquid storage. Two manufacturers supplied plastic multiple bag blood storage containers prefilled with modified CPD (glucose 25% greater than the normal concentration) supplemented with adenine (17.0 to 17.3 mg per 63 ml of anticoagulant; 0.25 millimolar approximate final concentration when diluted with 450 ml of whole blood for 35 days showed a mean survival of 80.53 +/- 6.44 per cent (1 SD). Both red blood cell and supernatant plasma biochemical characteristics were comparable to those reported for whole blood stored for 21 days in either acid-citrate-dextrose (ACD) or CPD. Red blood cells from 19 units stored as concentrates for 35 days (Hct 75.03 +/- 3.74%) had a mean survival of 71.38 +/- 10.3 per cent with considerable interdonor variation in survival and interlaboratory variation in some biochemical characteristics. Red blood cells from eight units stored as concentrates (Hct 75.38 +/- 4.30%) for 28 days showed a mean survival of 83.97 +/- 6.10 per cent and biochemical characteristics comparable to those reported for red blood cell concentrates stored in CPD or ACD for 21 days. Modified CPD with adenine as formulated offers an improved anticoagulant for blood banking by extending the permissible red blood cell storage period.