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Biomedical subjects

R G Strauss

Publications and source records attributed to R G Strauss.

At least 37 records · Page 2Linked to original sources

An international view of hydroxyethyl starches.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.

Blood Coagulation↗

Blood banking issues pertaining to neonatal red blood cell transfusions.

Many preterm infants are given multiple red blood cell transfusions during the early weeks of life. Because firm standards for neonatal transfusions do not exist, it is important to consider the pathophysiology of the anemia of prematurity, the goals of transfusion therapy and blood banking practices that best provide safe and effective neonatal transfusions. There is increasing agreement that efforts continue to minimize phlebotomy blood losses, to transfuse per conservative indications and to limit donor exposure by transfusing stored red blood cells from a single unit reserved for an infant--rather than insisting on fresh blood.

Blood Banks↗

Leukocyte-reduction to prevent transfusion-transmitted cytomegalovirus infections.

Certain infectious organisms, including cytomegalovirus, are associated 'exclusively' with blood leukocytes (WBC), and their transmission by transfusion is strikingly diminished by marked WBC-reduction of cellular blood components. Based on several reports of WBC-reduction, it is clear that the risk of CMV is nearly eliminated by consistently removing WBC to a level < 1-5 x 10(6) WBCs/unit (< or = 1 x 10(6) preferred in Europe; < or = 5 x 10(6) in the United States). Alternatively, the rate of CMV infections is reduced by transfusing blood components collected from donors negative for CMV antibody. However, neither technique is perfect, with a failure rate of 1-4%. Although WBC-reduction is favored by many experts, practitioners must choose the method that they believe to be most efficacious--being mindful that data do not exist to establish additive protection by combining WBC-reduction and transfusion of blood components collected from antibody negative donors.

Child↗

Cost-effectiveness of a limited-donor blood program for neonatal red cell transfusions.

BACKGROUND: Very-low-birthweight infants have typically been given fresh red cells (RBCs), a practice in which aliquots of RBCs for several infants were issued each day from a single unit. Recently, to limit donor exposures, large volumes of RBCs are reserved for the long-term transfusion support of individual infants. STUDY DESIGN AND METHODS: Medical records were examined retrospectively to assess the costs of a limited-donor program for providing RBC transfusions to very-low-birthweight infants. Costs of multiple- and limited-donor programs were compared by using two samples of 30 consecutive infants treated at The University of Iowa Hospitals and Clinics in 1993 and 1997. Effectiveness was evaluated with respect to the number of donor exposures per infant. RESULTS: The cost, in 1997 dollars, of preparing each small-volume transfusion in the multiple-donor program was $27.86 per transfusion, while that in the limited-donor program was $34.83. This difference was largely attributable to use of white cell reduction in association with the limited-donor program in 1997. Eliminating the costs associated with white cell reduction rendered the costs of the limited- and multiple-donor transfusions comparable. The limited-donor program had donor exposures of 2.0 per infant, while the multiple-donor program had 3.6 exposures per infant (p<0.002). CONCLUSION: The limited-donor blood program reduces donor exposure without adversely affecting costs.

Blood Donors↗

Antibodies provoked by the transfusion of biotin-labeled red cells.

BACKGROUND: Biotin-labeled (biotinylated) red cells (B-RBCs) offer a technique by which to study RBC volume and circulating kinetics without in vivo radiation. The immunogenicity of B-RBCs is undefined. STUDY DESIGN AND METHODS: To determine if biotinylation renders RBCs immunogenic, autologous B-RBCs were transfused to 20 healthy subjects, and plasma samples were obtained before transfusion and serially for up to 6 months after transfusion. These serial samples, plus plasma from 20 normal control subjects not given B-RBCs, were screened for antibodies to B-RBCs by use of an antiglobulin technique against aliquots of group O RBCs from a single donor-one aliquot biotinylated and one aliquot not biotinylated (i.e., test and control RBCs). Posttransfusion recovery and survival of B-RBCs were also determined. RESULTS: Plasma from none of 20 normal nontransfused subjects reacted with B-RBCs. Similarly, none of the 20 subjects given autologous B-RBC transfusions exhibited antibodies before transfusion. However, 3 of the 20 subjects transiently produced antibodies to B-RBCs after transfusion. Antibodies disappeared within 6 months in 2 of these 3 subjects and within 12 months in the third. Antibody reactivity was not reduced by dithiothreitol, but in 2 of the 3 subjects, B-RBC antibodies were neutralized by incubation with biotin solution. Circulating RBC kinetics were not altered in the 3 subjects with antibody. The significance of these observations is unclear, because antibodies were just beginning to emerge during the studies. CONCLUSIONS: Biotinylation does not render RBCs reactive with normal human plasma (i.e., presumably does not evoke neoantigens). Transfused B-RBCs occasionally provoke IgG antibodies in healthy subjects. Because the biologic effects of B-RBC antibodies currently are unknown, testing for them is recommended when multiple B-RBC transfusions are given to study RBC volume or circulating kinetics.

Biotin↗

Measurement of circulating red cell volume using biotin-labeled red cells: validation against 51Cr-labeled red cells.

BACKGROUND: Anemia is a serious problem in the fetus and preterm infant. To investigate the physiology and pathophysiology of anemia and to assess responses to blood transfusions or erythropoietin therapy, measurement of circulating red cell volume would be useful. Because the standard 51Cr method exposes the subject to radiation, a method of measuring circulating red cell volume without radiation exposure, sufficiently sensitive for use in fetuses and infants, was developed. STUDY DESIGN AND METHODS: In 10 healthy adults whose body mass ranged from 56.8 to 115.9 kg, aliquots of autologous red cells were labeled with biotin or with 51Cr, mixed, and transfused intravenously. Circulating red cell volume was measured in posttransfusion blood by quantitating the in vivo dilution of biotinylated red cells. Biotinylated red cells were detected by two methods: 1) 125I-streptavidin and 2) fluorescein-labeled avidin with flow cytometry. RESULTS: Circulating red cell volume measured by 125I-streptavidin detection agreed well with that measured by 51Cr (slope = 1.07, y-intercept = -97, correlation = 0.987). Similarly, circulating red cell volume measured by flow cytometry agreed well with that measured by 51Cr (slope = 1.05, y-intercept = -20, correlation = 0.987). CONCLUSIONS: Circulating red cell volume measured by the use of biotin with either 125I-streptavidin or flow cytometry agrees with that measured by 51Cr. Each system provides a method of performing these studies without exposing the subject to radiation.

Adult↗

Measurement of red cell survival using biotin-labeled red cells: validation against 51Cr-labeled red cells.

BACKGROUND: Anemia is a serious problem in the fetus and preterm infant.To investigate the physiology and pathophysiology of anemia and to assess responses to blood transfusions and erythropoietin therapy, measurement of circulating red cell survival would be useful. STUDY DESIGN AND METHODS: Because the standard 51Cr method exposes the patient or subject to radiation, a practical, accurate method for measuring red cell survival was developed on the basis of determining the number of biotin-labeled red cells that persist in the circulation by using fluorescein-labeled avidin and flow cytometry. In addition, disappearance of total biotin label was measured by using 125I-streptavidin. Results of each detection method were compared to red cell survival measured by the standard 51Cr method. RESULTS: Biotinylated cells persisted in circulation with life spans approaching normal. Despite near-normal persistence in circulation of the biotin-labeled cells, about one-half of the biotin label left the circulation over the first few weeks, causing early curvilinear disappearance. This observation is consistent with the hypothesis that about one-half of the biotin label leaves the red cells. However, about one-half of the biotin was permanently attached, which produced linear disappearance and approximately normal life span estimates for the linear survival curve appearing after the first few weeks. CONCLUSION: Red cell survival can be measured accurately in humans using enumeration of biotinylated red cells. The method is practical and does not expose the patient to radiation.

Adult↗

Fingerstick blood samples in platelet donor screening: reliability and impact on predict yield programs.

Although widely used, the reliability of fingerstick platelet counts for determining donor eligibility and for use with plateletpheresis predict yield programs has not been established. We compared platelet counts obtained from fingerstick vs. venous samples in several aspects of apheresis platelet collection. Analysis of 25 paired fingerstick and venous predonation samples demonstrated a poor correlation between platelet counts (r2 = .43), with fingerstick counts having a 20% lower mean value (P < .05). The effect of using fingerstick vs. venous predonation platelet counts with apheresis instrument predict yield calculations to obtain target yields was determined. Mean yields collected using fingerstick/predict yield were 12% (Fenwal CS3000 PLUS) and 15% (Haemonetics MCS+) higher than venous/predict yield units (P < .05). The coefficients of variation (CV) of fingerstick/predict yield and venous/predict yield collections were comparable (15% vs. 14% [CS3000] and 23% vs. 21% [MCS+], respectively), indicating that possible differences in accuracy between fingerstick and venous platelet counts had little effect on the variability of predict yield collections. A retrospective analysis of the CV of 100 fingerstick/predict yield units vs. 100 units collected by processing standard volumes showed no difference: 22% vs. 20% (F = 0.99, CS3000), and 22% vs. 24% (F = 0.89, MCS+), respectively. We conclude that fingerstick platelet counts are systematically lower and correlate poorly with venous counts, though their use seldom results in false disqualification of donors. We also conclude that fingerstick count/predict yield collections do not produce more consistent yields of platelets than standard volume collections.

Blood Donors↗

A survey of Canadian neonatal blood transfusion practices.

In 1990, the Pediatric Hemotherapy Committee of the American Association of Blood Banks developed and distributed a questionnaire addressing neonatal blood transfusion practices. The same questionnaire was subsequently sent to Canadian university-affiliated hospitals (n = 92). This report describes the results of the Canadian survey. Seventy-two percent (n = 66) of institutions contacted responded. Of these 42% (n = 28) had sufficient experience with neonatal transfusions and provided sufficient data for analysis. Although the majority of stated practices did follow published guidelines, several areas of variability and/or suboptimal practices were identified. With respect to component selection and preparation, suboptimal practices included excessive pretransfusion testing, unnecessary routine washing of RBC concentrates for small-volume transfusions, routine volume reduction of platelet concentrates and the use of suboptimal granulocyte preparations. With respect to transfusion practices, a disturbingly high percentage of respondents indicated that frozen plasma would be given in situations generally considered inappropriate. There was a great deal of variability in the provision of blood components at low risk for CMV, in the use of gamma irradiation and in the platelet count used for prophylactic platelet transfusions. The data collected in this survey provide information concerning practices that require improvement, identify areas where further research is desirable and provide a basis for comparison with current and future neonatal blood transfusion practices.

Blood Transfusion↗

Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL.

PURPOSE: We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS: Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS: There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION: Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.

Acute Disease↗

[14C]cyanate labeling of sheep red cells: covalent binding to hemoglobin continues in vivo for a day.

The sheep is a useful model to study fetal and newborn physiology including perinatal erythropoiesis and red cell kinetics. A practical, economical method for measuring red cell survival (RCS) in sheep would be very valuable. However, 51Cr is unsatisfactory, and suitable alternatives have not been published. In the course of investigating [14C]cyanate as a label for sheep red cells, we observed continued covalent labeling over 24 h in vivo that was great enough to introduce a substantial artifact into two commonly used parameters of RCS: posttransfusion recovery (PTR24) and time to 50% decrease (T50) when referenced to time zero. In a simulation of in vivo conditions, the amount of 14C bound to Hb increased 26 +/- 6% (mean +/- 1 SD, n = 11) over 24 h. To investigate the mechanism of the increasing 14C bound, acid-acetone extraction, molecular sieve chromatography, and density gradient separation were used separately or in combination to quantitate intracellular free 14C and 14C covalently bound to intracellular proteins. Free 14C decreased as protein-bound [14C]cyanate increased. These studies provide evidence that covalent binding of [14C]cyanate to intracellular Hb continues in vivo for the first 24 h and that the source of the increase is intracellular free [14C]cyanate. We conclude that 1) PTR24 cannot be accurately determined by [14C]cyanate unless labeled red cells are incubated before infusion to allow the cyanate reaction to approach completion and 2) RCS by [14C]cyanate should be referenced to blood concentrations at 24 h.

Acetone↗

Circulating red cell volume and red cell survival can be accurately determined in sheep using the [14C]cyanate label.

The sheep commonly serves as an animal model for investigation of human fetal and newborn erythropoiesis and red blood cell kinetics. Measurement of red cell volume (RCV) and survival (RCS) in sheep would be useful for studying mechanisms of neonatal anemia. Unfortunately 51Cr, the standard method for RCV, is not suitable for RCS in sheep because 51Cr leaves the red cell too rapidly. We developed and validated the permanent label [14C]cyanate as a method for measuring both RCV and RCS in sheep. In 19 sheep, RCV was determined simultaneously using [14C]cyanate and 51Cr. RCV determined by [14C]cyanate agreed almost perfectly with RCV by 51Cr; correlation coefficient = 0.990. The line of regression had a slope of 0.94 and an intercept of 40; these parameters are not significantly different from a line of identity. In nine sheep, RCS was determined using [14C]cyanate. Survival after d 1 accurately fit a model containing two components: 1) an early exponential loss likely related to damage caused by labeling and handling and 2) a linear decrease that reflected normal survival of undamaged red cells. Mean potential life span (MPL) determined from the linear phase was 114 +/- 12 d (mean +/- 1 SD). These results agree with reported MPL values determined either by 59Fe or differential hemolysis. Together, these observations establish [14C]cyanate-labeled red cells as a tool for measuring both RCV and RCS in sheep and enhance the value of the ovine model for investigating neonatal anemia.

Anemia↗

Practical issues in neonatal transfusion practice.

Small premature infants frequently require transfusions of blood components, particularly red blood cells (RBCs), during the first weeks of life. Although great efforts have been made during the past few years to optimize the transfusion of blood components to these tiny patients, several questions have not been definitively answered. Accordingly, transfusion practices vary among neonatologists. The purpose of this article was to assess the available data critically. The findings indicated that stored RBCs can be transfused safely into premature infants to diminish donor exposures. It was also found that leukocyte-reduced blood components can be used to prevent the transmission of cytomegalovirus; thus, cellular components do not need to be obtained exclusively from donors negative for antibodies to cytomegalovirus. However, gamma-irradiation of cellular blood components cannot be justified for all neonatal transfusions. Obviously, as new information is reported, these findings may require revision.

Blood Banks↗

Providing leukocyte-reduced platelets using the CS-3000 PLUS.

Reducing leukocyte (WBC) contamination of platelet (PLT) concentrates diminishes some adverse effects associated with transfusions. To provide WBC-reduced PLTs, we initiated a program using bedside filtration. However, the inability to easily quantitate WBC removal and PLT loss at the bedside prompted us to perform filtration in the blood bank. To establish optimal methods, production of WBC-reduced PLTs using the CS-3000 PLUS was studied in three phases, during which technical modifications were made. During phase 1, prestorage WBC reduction was performed using the PALL LRF-10H filter, sterilely connected. WBC reduction was satisfactory, but PLT loss was excessive. During phase 2, the PLT-30 collection chamber and Fenwal Closed System Apheresis Kit with Integral Sepacell Leukocyte Reduction Filter were used. PLT yields were improved, but now WBC contamination was excessive. During phase 3, the interface offset was reduced from 10 to 6, and both PLT yields and WBC reduction were satisfactory. Using this final method (CS-3000 PLUS, PLT-30 collection chamber, integral filter and offset setting of 6), the mean PLT yield per unit is 4.29 x 10(11) (N = 1,146), and the mean WBC contamination is 0.50 x 10(6) (N = 32).

Blood Banks↗