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Biomedical subjects

M E Brecher

Publications and source records attributed to M E Brecher.

At least 19 recordsLinked to original sources

Bacterial contamination of blood products: factors, options, and insights.

Transfusion of bacterially contaminated blood products remains an overlooked problem. However, the risk of receiving a bacterially contaminated unit is greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this article include: the current incidence, clinical presentation and outcome, effective methods of detection, and ways to reduce bacterial contamination of blood products. There is no one existing strategy that can completely eliminate the risk of bacterial contamination. It is inevitable that partial solutions or combinations of methods will be implemented in the near future.

Bacteremia↗

Incidence of allergic reactions with fresh frozen plasma or cryo-supernatant plasma in the treatment of thrombotic thrombocytopenic purpura.

Plasma replacement for thrombotic thrombocytopenic purpura (TTP) is accomplished with various plasma products. This study sought to determine the incidence of allergic reactions with FFP or CPP as replacement in therapeutic plasma exchange (TPE). Forty-one TTP patients were identified retrospectively who received TPE replacement with either FFP (n=21) or CPP (n=20). Anti-histamine was administered prophylactically following the initial occurrence of an allergic reaction (urticaria, respiratory distress, or anaphylaxis with hypotension). Fifty-one allergic reactions occurred in 65.8% of patients. Urticaria comprised 49 of 51 (96%) of reactions and respiratory distress the remaining 4%. No anaphylaxis occurred. Nineteen urticarial reactions occurred in 50% of CPP recipients compared to 71% of FFP recipients (P=0.28). Anti-histamine breakthrough occurred in 36.3% of patients who experienced a previous allergic reaction with CPP and 37.5% with FFP (P=1.0). The overall risk of allergy per unit of plasma was 1.37% (1.23 % CPP, 1.48% FFP), comparable to estimates in non-TTP recipients. The median number of donor exposures preceding the first allergic reaction was 35 and 32, CPP and FFP, respectively (P=0.63). The mean volume of plasma transfused prior to reaction was 9,883 mL for CPP and 9,348 mL for FFP (P=0.85). Neither product was advantageous in preventing allergic complications. Because of the large volume, the number of donor exposures, and prolonged duration of therapy, allergic reactions to plasma are common (65.8%) in the treatment of TTP.

Blood Preservation↗

Evaluation of an automated culture system for detecting bacterial contamination of platelets: an analysis with 15 contaminating organisms.

BACKGROUND: Approximately 1 in 2000 platelet components are bacterially contaminated. The time to detection of 15 seeded organisms in platelets recovered from an automated culture system was studied. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Bacillus subtilis, Candida albicans, Clostridium perfringens, Corynebacterium species, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus pyogenes, and Streptococcus viridans were inoculated into Day 2 apheresis platelet components to obtain a final concentration of approximately 10 and 100 CFU per mL (2 units/organism). Each bag was sampled 10 times (20 mL/sample). Four mL of each sample was inoculated into standard aerobic and anaerobic bottles and into aerobic and anaerobic bottles containing charcoal; 2 mL was inoculated into pediatric aerobic bottles (so as to maintain a 1:10 ratio of sample to media) and 1 mL into thioglycollate broth. RESULTS: With the exception of P. acnes, all organisms were detected in a mean of 9.2 to 25.6 hours. A range of 10 serial dilutions in inoculating concentrations was associated with an overall 10.1-percent difference in detection time. A mean of 74.4 and 86.2 hours (100 and 10 CFU/mL inocula, respectively) was required for the detection of P. acnes in anaerobic bottles. CONCLUSION: Bacteria thought to be clinically significant platelet contaminants can be detected in 9.2 to 25.6 hours when the starting concentration is approximately 10 to 100 CFU per mL. P. acnes required considerably longer incubation times for detection (in either aerobic or anaerobic bottles). However, P. acnes is of questionable clinical significance. Such a detection system could be used in either a blood collection center or a transfusion service to screen platelet concentrates for bacterial contamination. Such testing (with sterile sampling performed so as to maintain a closed-bag system) would be expected to save lives and might allow an extension of platelet storage.

Bacteria↗

Number of RBC units and rate of transfusionto anemic HIV-positive patients assigned to receiveWBC-reduced or non-WBC-reduced RBCs: the viral activation transfusion study experience.

BACKGROUND: It is known that the use of filtration to reduce WBCs in RBC units is associated with a 6- to 15-percent loss of RBCs. It is not known if the use of such WBC-reduced RBCs results in an increased need for RBC units or in the transfusion of more units per year to patients with anemia. STUDY DESIGN AND METHODS: In the multicenter Viral Activation Transfusion Study (VATS), anemic HIV-positive patients were randomly assigned to receive either WBC-reduced or non-WBC-reduced RBCs. The number of RBC units transfused per patient and the rate of RBC use were studied. All RBC units given after the enrollment transfusion were counted, until the end of follow-up or the occurrence of bleeding (receiving >5 RBCs within 2 consecutive days). RESULTS: As expected, the WBC-reduced RBC units in VATS were lighter in weight than the non-WBC-reduced units (median weight: WBC-reduced, 300 g; non-WBC-reduced, 330 g; p<0.0001). After the enrollment transfusion, 258 WBC-reduced arm patients received 1279 units of RBCs (average, 5.0 units/patient, median, 2 units) while 262 patients in the non-WBC-reduced arm received 1111 RBCs (4.2 units/patient; median, 2 units). The number of units transfused for anemia was slightly greater in the WBC-reduced arm, but the difference was not significant (p = 0.41). Similarly, the rate of RBC use was somewhat higher in the WBC-reduced arm, but the difference was not significant (p = 0.14). The median was 2.3 units per patient per year of follow-up in the WBC-reduced arm; the median in the non-WBC-reduced arm was 1.2 units. CONCLUSION: This study confirms that WBC-reduced RBC units are significantly lighter in weight than non-WBC-reduced RBCs. However, in the setting of a large, randomized, blinded study of transfusion for anemia, the smaller size of the WBC-reduced RBC units had no significant effect on the number of RBC units transfused or on the rate at which RBC units were used. In this study, the frequency of blood transfusion may have had a greater relationship to the frequency of routine, scheduled appointments or transfusion orders for a specified Hb trigger than to the actual Hb content of the unit.

Anemia↗

In vivo and in vitro characteristics of double units of RBCs collected by apheresis with a single in-line WBC-reduction filter.

BACKGROUND: A novel apheresis procedure for a blood separator (MCS+, Haemonetics) enables the collection of 2 WBC-reduced RBC units in a single donation by using one disposable set with one in-line WBC-reduction filter (RC2H, Pall Corp.). The objective of this study was to evaluate the filtration performance in connection with different prefiltration RBC storage conditions and with the in vitro and in vivo storage quality of the filtered units. STUDY DESIGN AND METHODS: Sixty-six 2-unit RBC collection and gravity-filtration procedures were completed at three sites, resulting in 132 RBC units. Filtration of the double RBC units was performed at room temperature (RT) within 8 hours of collection (n = 36) and under refrigeration (1-6 degrees C) for up to 24 hours (n = 10) and 72 hours (n = 20) before filtration. RBC quality was compared to that of nonfiltered apheresis RBC units (n = 10). RESULTS: Median filtration time was 6.5 and 14 minutes for units stored at RT and under refrigeration, respectively. All 132 RBC units had residual WBC counts <0.4 x 10(6). The refrigerated units showed a greater mean log reduction in WBCs: 5.06 +/- 0.16 (24 hour) and 4.74 +/- 0.48 (72 hour), respectively, than did RT units: 4.47 +/- 0.28 (p<0.05). RBC loss was less than 12 percent in all cases (mean, 7.8 +/- 1.8%). Minimal differences in volume were observed between the paired RBC units. In vitro RBC storage characteristics of the filtered units were as expected and similar to those of the nonfiltered units. For RBC units held at RT (n = 24), the mean in vivo 24-hour recovery was 81.8 +/- 8.4 percent (double-label). CONCLUSION: Satisfactory filter performance in terms of WBC removal and RBC loss was observed with all 66 procedures, irrespective of storage conditions before filtration.

Blood Component Removal↗

Transfusion-related bacterial sepsis.

Transfusion-associated bacterial sepsis is a persistent problem in transfusion medicine, posing a greater threat than the combined risks of receiving a blood product contaminated with HIV-1 or 2, hepatitis C virus (HCV), hepatitis B virus (HBV), and human T-cell lymphtrophic virus (HTVL) -I or -II. This article provides a brief overview of the current incidence, clinical presentation, associated blood products and organisms, and the most feasible and effective methods available to reduce the potential risk of transfusion-associated sepsis. Because bacterial contamination of blood products is the most frequent cause of transfusion-transmitted infectious disease, and as no single existing strategy can completely eliminate its risk, it is important that clinical suspicion be high, and any partial solutions additively be implemented.

Animals↗

Comparison of granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells and G-CSF--stimulated bone marrow as a source of stem cells in HLA-matched sibling transplantation.

HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.

Adolescent↗

Antibiotic-labeled probes and microvolume fluorimetry for the rapid detection of bacterial contamination in platelet components: a preliminary report.

BACKGROUND: Approximately 1 platelet in 2000 components is bacterially contaminated. Most commonly, contaminating organisms are gram positive skin saprophytes (such as Staphylococcus sp. or Bacillus sp.). A novel approach to the rapid diagnosis of gram positive contamination by the use of a fluorescence-labeled antibiotic probe with affinity for the gram positive cell was investigated. STUDY DESIGN AND METHODS: Two isolates of Staphylococcus epidermidis were inoculated into bags of Day 0 platelets. Quantitative cultures along with a semi-automated screening assay on a microvolume fluorimeter employing a fluorescence-conjugated vancomycin probe was performed for each day of storage. In addition, serial dilutions of the bacteria were added to sterile platelets to achieve a range spanning 10(1) to 10(8) CFUs per mL. RESULTS: All samples with a bacterial contamination of > or =10(5) CFU per mL were detected. Sterile samples were nonreactive. The entire procedure requires three pipetting steps and took less than 1 hour to perform. CONCLUSION: These preliminary results with the use of fluorescence-labeled antibiotics as probes combined with microvolume fluorimetry for the rapid detection of bacterial contamination of platelet components suggest that this is a promising approach. Further studies with additional organisms and alternative conjugates, bacteria, and antibiotics are underway.

Anti-Bacterial Agents↗

Growth of bacteria in inoculated platelets: implications for bacteria detection and the extension of platelet storage.

BACKGROUND: Recent reports from Europe have advocated the use of bacterial culturing of platelets on Day 2 or 3 of storage to extend the shelf life of platelets to 7 days, thereby reducing the outdating of platelets and preserving a limited medical resource. To assess the optimal timing, the necessary sensitivity, and the possible efficacy of bacterial detection, the bacterial growth characteristics were reviewed in 165 platelet units, each inoculated on the day of collection with one of the following organisms: Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, and Staphylococcus epidermidis from four previously published studies. STUDY DESIGN AND METHODS: Quantitative culture data from inoculated platelet concentrates from five sites and four studies were combined into one database and analyzed for bacterial concentration thresholds (> or =10(1), > or =10(2), > or =10(3), > or =10(4), > or =10(5) CFU/mL) by day of storage. RESULTS: All examples of B. cereus, P. aeruginosa, K. pneumoniae, S. marcescens, and S. aureus had concentrations > or =10(2) CFU per mL by Day 3 after inoculation. By Day 4, all units with these organisms contained > or =10(5) CFU per mL. Units contaminated with S. epidermidis showed slower and more varied growth. By Day 3 after inoculation, 81.3 percent had 10(2) CFU per mL. By Day 4 after inoculation, 46 (95.8%) of 48 units had concentrations > or =10(2) CFU per mL. CONCLUSION: These experiments suggest that an assay capable of detecting 10(2) CFU per mL on Day 3 of storage would detect the vast majority of bacterially contaminated platelet units, prevent many cases of platelet-associated bacterial sepsis, and provide a scientific basis for the extension of the current platelet storage time. It would be expected that a rare, slow-growing organism could escape such a detection scheme.

Bacteria↗

Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management.

Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized. The possible role of occult infection and newly emerging associations such as ticlopidine therapy are discussed. Advances in possible pathogenic mechanisms, the rationale for different replacement fluids including the recently licensed solvent-detergent treated plasma, and progress in the apheresis management of TTP syndrome are presented.

Blood Component Removal↗

Where does preoperative erythropoietin therapy count? A mathematical perspective.

BACKGROUND: The administration of erythropoietin (EPO) can be used to increase a patient's hematocrit (Hct) in the preoperative period and thus possibly preclude the need for allogeneic red cells. However, the exact effect on the postoperative Hct of a given rise in Hct in the preoperative period (and on the avoidance of allogeneic blood) has not been thoroughly evaluated. STUDY DESIGN AND METHODS: Equations were developed on the basis of previously described relationships that allowed the assessment of the impact of a given preoperative Hct increase on the postoperative Hct under a variety of clinical situations. RESULTS: Equations were derived that related the change in preoperative Hct after the administration of EPO to the final Hct after a given blood loss. In a typical example (blood volume = 5000 mL, pre-EPO Hct of 40%, post-EPO Hct of 45% after blood losses of 1000, 2000, 3000, 4000, 5000, and 6000 mL), an additional 205, 168, 137, 112, 92, and 75 mL of red cells, respectively, would be present postoperatively over the volume in the same patient who did not receive EPO. For a smaller patient, such as a child (blood volume, 2500 mL), an additional 17 mL (5000-mL blood loss) to 83 mL (1000-mL blood loss) of red cells would be present postoperatively. Hemodilution and EPO act synergistically to yield additional postoperative red cell volume. CONCLUSION: The use of preoperative EPO with a preoperative increase in Hct results in an increased postoperative Hct after a surgical blood loss. Such a postoperative increase is a function of the volume of blood lost and the patient's blood volume but is independent of the patient's initial Hct. The final postoperative red cell volume increase associated with a preoperative increase in Hct of 1 to 5 percent is limited, however (generally equivalent to a fraction of 1 unit of allogeneic blood). Much of the increase in the patient's Hct vanishes at higher blood losses, and this therapy is most effective with blood loss of <4000 mL. EPO therapy alone may be most effectively used in patients with mild anemia who are undergoing routine surgical procedures that commonly require blood transfusion.

Blood Loss, Surgical↗