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Mark E Brecher

Publications and source records attributed to Mark E Brecher.

At least 19 recordsLinked to original sources

Summary of the AABB Interorganizational Task Force on Bacterial Contamination of Platelets: Fall 2004 impact survey.

BACKGROUND: New voluntary standards in the United States regarding bacterial contamination of platelets (PLTs) led to the formation of the AABB Interorganizational Task Force on Bacterial Contamination of Platelets. This article summarizes a survey conducted by the Task Force to assess the impact of bacterial detection. STUDY DESIGN AND METHODS: An Internet-based survey of AABB member institutions was conducted from September 17, 2004, to October 1, 2004. The survey was designed principally to assess PLT usage, supply, and outdating and the currently used bacteria detection methods. RESULTS: Of 900 facilities surveyed, 350 responded (38%). These facilities collected approximately 43.3 and 65.9 percent and transfused approximately 19.1 and 22.2 percent of the whole blood-derived PLT concentrates (WBPCs) and apheresis PLTs in the United States, respectively. Most facilities (64-91%) indicated that their ability to provide PLTs for transfusion had not been affected. Approximately half (50-57.1%) indicated no changes in their PLT inventory. Two-thirds (66-68%) indicated no increased PLT outdating. More than 90 percent of apheresis PLTs are tested with a culture-based method, whereas WBPCs are tested with a variety of methods (mostly non-culture-based) resulting in a 4.6-fold decrease in the confirmed positive detection rate compared with apheresis PLTs (p < 0.001). CONCLUSION: After the implementation of AABB Standard 5.1.5.1, the majority of facilities responding to this survey experienced no (or modest) impact on PLT availability or outdating. Nevertheless, a substantial portion of facilities experienced both increased outdating and decreased availability. Some facilities were greatly impacted. Based on the data gathered, it is impossible to conclude whether such shortages resulted from production or distribution problems or were due to decreased shelf life and increased outdates.

Bacteria↗

How I approach a thrombotic thrombocytopenia purpura patient.

In the past few years, advances in the understanding of the pathophysiology of thrombotic thrombocytopenic purpura (TTP) has made great strides; however, this has yet to significantly impact the clinical care of patients. Although the use of daily plasma exchange is evidence-based and well established, many of the facets of clinical care remain largely empiric. Our laboratory has had a sustained interest in studying and optimizing the use of plasma exchange in TTP patients. This article presents a summary of how our clinical service approaches TTP patients and manages commonly occurring problems.

Female↗

Life, death, and the risk of transfusion: a university hospital experience.

BACKGROUND: Frequently one encounters donor recruitment statements like ". . . about 90 percent of American adults will need at least one blood transfusion in the course of a lifetime." To assess the validity of such statements, the lifetime transfusion rate of patients dying in our tertiary-care hospital was determined. It would be expected that patients dying in a tertiary-care, Level 1 trauma center university hospital would have one of the highest transfusion rates. STUDY DESIGN AND METHODS: A retrospective review of blood bank and electronic clinical records was conducted for all patients who expired at our institution from January 1, 2004, through December 31, 2004. Stillborn infants were excluded from analysis. The rate of transfusion was stratified by age and sex. RESULTS: A total of 906 patients expired in 2004 at our institution. Of these, 35 were excluded (stillborn infants), leaving 871 patients for analysis. After review of blood bank records, 591 patients received blood products (67.9%). An additional 27 patients (3.1%) had a possible transfusion at another institution as the clinical record indicated complex surgical history. Only 253 patients (29.0%) did not have a documented transfusion event. Individuals who died before the age of 31 had the highest rates of transfusion (p < 0.001, Fisher's exact test, two-sided). CONCLUSIONS: The majority of patients who expire at our institution have a history of transfusion (67.9%-71.0%). Patients who die before the age of 31 have the highest rate of transfusion.

Age Distribution↗

Patterns of platelet response in idiopathic TTP/HUS: frequency of declining platelet counts with plasma exchange and the recognition and significance of a pseudo refractory state.

For thrombotic thrombocytopenic purpura (TTP), daily plasma exchange (TPE) is typically discontinued when the platelet count normalizes (>150 x 10(9)/L). We observed a decline in platelet count during TPE and in patients who appeared pseudo-refractory because of a platelet count plateau (100-150 10(9)/L range). In the present study, we evaluated platelet count trends in TTP patients. Retrospective review of TTP patients from 01/1999 to 12/2004 was completed. Patients were categorized based on platelet count trends: Group I, counts rose then decreased to levels <100 x 10(9)/L; Group II, counts declined following TPE initiation; Group III, counts rose continuously; Group IV, counts decreased after the count was >100 x 10(9)/L. Additionally, we identified pseudo-refractory patients caused by a platelet count plateau (>100 x 10(9)/L but <150 x 10(9)/L). We identified 60 TTP patients. Within Group I (17 patients/17 series/19.1% of total), the mean decrease in platelet count was 67.3% +/- 22.1% following initial rise. Within Group II (24 patients/25 series/28.1% of total), the mean decrease was 28% +/- 5.3% following presentation. Group III included 31 patients/39 series (43.8% of the total). Within Group IV (seven patients/eight series/9.0% of total), the mean decrease was 17.4% +/- 12.6% following a sustained rise >100 x 10(9)/L. With a declining platelet count and daily TPE, it is generally sufficient to stay the course and the decline will reverse. Our limited experience with pseudo-refractory patients supports discontinuing TPE when counts plateau between 100 and 150 x 10(9)/L when a therapy goal is a platelet count of 150 x 10(9)/L. Recognition of this pseudo-refractory state can minimize the risks of prolonged TPE and the risks of adjunct interventions.

Adolescent↗

Protecting the blood supply from emerging pathogens: the role of pathogen inactivation.

Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid-containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.

Anti-Infective Agents↗

Bacterial contamination of blood components.

Blood for transfusion is a potential source of infection by a variety of known and unknown transmissible agents. Over the last 20 years, astounding reductions in the risk of viral infection via allogeneic blood have been achieved. As a result of this success, bacterial contamination of blood products has emerged as the greatest residual source of transfusion-transmitted disease. This paper summarizes the current status of detection, prevention, and elimination of bacteria in blood products for transfusion.

Bacteremia↗

Dendritic cells can be rapidly expanded ex vivo and safely administered in patients with metastatic breast cancer.

PURPOSE: Immunotherapy using either dendritic cells (DCs) or expanded cytotoxic T cells (CTLs) has received increased interest in the treatment of specific malignancies including metastatic breast cancer (MBC). DCs can be generated ex vivo from monocytes or CD34+ precursors. The ability to expand and safely administer CD34-derived DCs in patients with MBC that have received prior cytotoxic chemotherapy has not been evaluated. METHODS: We enrolled ten patients with MBC that had received prior chemotherapy for the treatment of metastatic disease on a phase I/II trial designed to test the safety and feasibility of administering ex vivo expanded DCs from CD34+ progenitor cells. RESULTS: Using a cocktail of multiple different cytokines, we could expand DCs 19-fold compared to the initial CD34-selected product, which allowed the administration of as many as six vaccine treatments per patient. Patients received three to six injections i.v. of DCs pulsed with either the wild type GP2 epitope from the HER-2/neu protein or an altered peptide ligand, isoleucine to leucine (I2L). Toxicity was mild, with no patients demonstrating grade III toxicity during the treatment. Two patients with subcutaneous disease had a partial response to therapy, while IFN-gamma-producing CD8+ T cells could be found in two other patients during treatment. CONCLUSIONS: This approach is safe and effective in generating a significant quantity of DCs from CD34-precursors.

Adult↗

Frequency and significance of schistocytes in TTP/HUS patients at the discontinuation of plasma exchange therapy.

INTRODUCTION: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is characterized by thrombocytopenia, a microangiopathic hemolytic anemia (presence of schistocytes) and elevated LDH without another likely explanation. Standard of care is daily plasma exchange, which is typically discontinued when the platelet count exceeds 100-150 x 10(9)/L for 2 days. However, residual schistocytosis, the presence of schistocytes at the time of discontinuation of plasma exchange therapy, is often disconcerting. We evaluated the frequency and significance of residual schistocytosis in TTP/HUS patients when the patients' platelet counts returned to normal levels (e.g., 100-150 x 10(9)/L). METHODS: Retrospective review in our institution from 01/1999-03/2004 of all patients treated with plasma exchange for TTP/HUS with at least 2 months of follow-up for relapse was completed. Patients were excluded if the clinical course was complicated by HIV, stem cell/bone marrow and solid organ transplant, pregnancy and auto-immune disease. Schistocytes were documented on day of presentation and on the day the platelet count reached 150 x 10(9)/L. Grading scale (using 100 x objective-a high power field, with approximately 100 red blood cells per field) for schistocytes was as follows: rare for 1 schistocyte per every other other field, 1+ for 1-5%, 2+ for 6-15%, and 3+ for >15%. The frequency of schistocytes was compared to frequency of relapse within 2 months, using Fisher's exact test. RESULTS: We identified 57 patients with TTP/HUS who received plasma exchange therapy. Of these patients, 12 did not have a follow-up microscopic examination of a peripheral blood smear at discontinuation of plasma exchange therapy and were excluded from further analysis. Of the remaining 45 patients, 16 had residual schistocytosis (35.6%). There was no statistically significant difference in relapse rate with or without residual schistocytosis (P = 1.00, Fisher's Exact test, 2 sided). CONCLUSIONS: In this study, we found that the presence of residual schistocytosis is common (35.6%). The presence of residual schistocytosis, however, was not predictive of relapse.

Erythrocytes, Abnormal↗

Improving platelet safety: bacterial contamination of platelets.

In developed countries, transfusion-transmitted bacterial contamination of platelets is the most common cause of fatalities related to transfusion-transmitted disease. Platelets, to maintain viability and function, must be stored at room temperature (20 degrees-24 degrees C), which creates an excellent growth environment for the proliferation of bacteria. Multiple studies have shown that 1:1000 to 1:2000 platelet units are bacterially contaminated. It is estimated that the risk of a bacterial-related death after a transfusion of a platelet unit ranges from 1:7500 to 1:100,000. The use of bacterial detection to minimize the risk of transfusion-related bacterial sepsis is gaining favor around the world. Implementation of bacterial detection methods would improve safety for patients, result in an extension of the shelf life of platelets, and reduce the outdating of platelets, thus being a cost-saving safety intervention.

Accreditation↗

Transfusion medicine: looking to the future.

The evolution of transfusion medicine into a clinically oriented discipline emphasising patient care has been accompanied by challenges that need to be faced as specialists look to the future. Emerging issues that affect blood safety and blood supply, such as pathogen inactivation and more stringent donor screening questions, bring new pressures on the availability of an affordable blood supply. Imminent alternatives for management of anaemia, such as oxygen carriers, hold great promise but, if available, will require close oversight. With current estimates of HIV or hepatitis C viral (HCV) transmission approaching one in 2000000 units transfused, keeping to a minimum bacterial contamination of platelet products (one in 2000) and errors in transfusion, with its estimated one in 800000 mortality rate, assume great urgency. Finally, serious difficulties in blood safety and availability for poor, developing countries require innovative strategies and commitment of resources.

Blood Banks↗

An expanded phase I/II trial of cyclophosphamide, etoposide, and carboplatin plus total body irradiation with autologous marrow or stem cell support for patients with hematologic malignancies.

The major cause for failure of autologous stem cell transplantation for hematologic malignancies is the risk of recurrent disease. As a result, new treatment regimens that include novel agents or combinations of agents and approaches are needed. The current report describes a large Phase I/II, single-center trial that includes 60 patients with a variety of hematologic malignancies. These patients received a fixed dose of carboplatin (1 g/m(2)/d x 72 hours by CI) etoposide (600 mg/m(2)/d x 3 days) and cyclophosphamide (2 g/m(2)/d x 3 days), plus escalating doses of total body irradiation (TBI) (at 1000, 1200, and 1295 cGy) over 3 days. Eleven patients received infusion of autologous marrow, 32 received peripheral blood stem cells, and 17 patients received both. The maximum tolerated dose of this regimen was a radiation dose of 1200 cGy given in 200-cGy fractions BID x 3 days. The dose-limiting toxicity was mucositis, with 97% of patients requiring narcotic analgesia for mouth pain. Overall treatment-related mortality was 6.7%, with 2 of the 4 deaths occurring in a group of 9 patients aged 60 and older. Responses were seen in all patient groups, but the most encouraging outcomes were seen in 12 patients with high-risk or advanced acute myelocytic lymphoma (AML), 7 of whom remain alive and free of disease beyond 5 years. This regimen is intensive and causes considerable mucositis but is otherwise well tolerated and has demonstrated activity in a number of hematologic malignancies, especially AML.

Adult↗