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Biomedical subjects

R Yomtovian

Publications and source records attributed to R Yomtovian.

At least 19 recordsLinked to original sources

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Adolescent↗

Consanguineous hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection treated with aggressive therapeutic plasma exchange.

We describe the successful management of an elderly husband and wife with Escherichia coli O157:H7 associated hemolytic uremic syndrome (HUS) treated with aggressive therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma. Following twelve TPEs (three 1.5 volume; nine 1 volume), the husband's platelet count increased from 45 x 10(9)/L to 183 x 10(9)/L. Following ten 1.5 volume TPEs, the wife's platelet count increased from 30 x 10(9)/L to 193 x 10(9)/L. This is the first known occurrence of E. coli O157:H7 associated HUS in an elderly husband and wife successfully treated with aggressive TPE. We conclude that early, aggressive TPE should be considered and may be life-saving for E coli O157:H7 associated HUS in the elderly.

Aged↗

WBC reduction in RBC concentrates by prestorage filtration: multicenter experience.

BACKGROUND: As universal leukocyte (WBC) reduction (ULR) is being considered as a new standard, few data are available on the performance of WBC-reduction filtration in routine practice. The performance of WBC-reduction in RBCs, using varied filtration practices, in meeting the current FDA requirement (<5 x 10(6)), Council of Europe (EC) recommendation, the proposed FDA requirement (<1 x 10(6)), and a more stringent proposal (<5 x 10(5)) for residual WBCs per RBC unit was assessed and compared. STUDY DESIGN AND METHODS: Participating facilities were the 11 sites of the Viral Activation Transfusion Study (VATS), a prospective study of the impact of transfusion with and without WBC-reduction on survival and HIV viral load in HIV-1-infected patients. Patients randomly assigned to undergo WBC reduction were required to receive RBCs < or =14 days old that had undergone prestorage (within 72 hours of collection) WBC-reduction filtration by a method devised to achieve a postfiltration WBC count of <5 x 10(6). Residual WBC quantitation was performed by PCR in the central VATS laboratory by using frozen WBC-reduced RBC samples obtained at issue for transfusion. RESULTS: A total of 1869 WBC-reduced RBC units were studied. Filtration practices varied within and between sites. There were significant differences in mean residual WBC counts at the 11 sites (p<0.001). Among the WBC-reduced RBC units, 0.8 percent exceeded 5 x 10(6) WBCs per unit, 8.3 percent exceeded 1 x 10(6) WBCs per unit, and 14.3 percent exceeded 5 x 10(5) WBCs per unit. CONCLUSION: Residual WBCs in WBC-reduced RBC units vary within and between sites. WBC reduction was successful, in that over 99 percent and 91 percent of VATS WBC-reduced RBC units met US and EC thresholds, respectively. However, the small but measurable failure rate indicates that not every unit will meet these guidelines.

Blood Component Removal↗

Methicillin-resistant Staphylococcus aureus sepsis associated with the transfusion of contaminated platelets: a case report.

BACKGROUND: Platelet transfusion-associated sepsis is usually due to donor skin flora introduced into the unit during phlebotomy. An unusual case of a platelet component contaminated with methicillin-resistant Staphylococcus aureus (MRSA) is reported. CASE REPORT: A 54-year-old man, terminally ill with progressive non-Hodgkin's lymphoma, developed fever and hypotension during a platelet transfusion. He was receiving multiple antibiotics, including vancomycin. Blood cultures taken soon after transfusion were negative. An aliquot taken from the platelet pool grew MRSA at a count of 1.6 x 10(8) CFUs per mL. One of the individual bags constituting the pool showed MRSA at a count of 5.1 x 10(8) CFUs per mL. The patient died soon after the platelet transfusion. This case was reported to the FDA and submitted to the BaCon Study. The identity of the isolate and its methicillin resistance were confirmed by the CDC as part of the BaCon Study protocol. The source of contamination of the implicated unit could not be established with certainty. CONCLUSION: The emergence of antimicrobial-resistant organisms poses additional challenges for the diagnosis and treatment of transfusion-associated sepsis. Measures to prevent or intercept the transfusion of contaminated platelets should be developed.

Blood Platelets↗

Successful large volume leukapheresis on a small infant allogeneic donor.

We successfully performed a hematopoietic stem cell apheresis on the smallest allogeneic donor reported to date, a 6.1 kg female. After placement of a dialysis catheter in the left femoral vein, the COBE Spectra was primed with one unit of paternal whole blood. Heparin and anticoagulant citrate dextrose, solution A (ACD-A) were slowly administered to the patient. Ionized calcium levels were checked hourly and calcium gluconate was given for hypocalcemia. Coagulation parameters were checked throughout the procedure. We collected 4.4 x 10(6) CD34+ cells/kg (recipient). The donor tolerated the procedure well and was discharged the following day. Five months later, the child manifests no obvious late effects.

Female↗

Heparin-induced coagulopathy associated with staphylococcal protein A immunoadsorption treatment columns: an in vitro and in vivo analysis.

BACKGROUND: The staphylococcal protein A (SPA) column used to treat refractory autoimmune and alloimmune thrombocytopenia and rheumatoid arthritis patients is primed with heparin to prevent possible fibrin clot formation when the patient's plasma is passed through the column. A BMT patient with refractory alloimmune thrombocytopenia had prolonged activated partial thromboplastin times (aPTTs) at the end of SPA column treatments. This observation led to in vivo and in vitro analysis of the kinetics of heparin elution from the SPA column. STUDY DESIGN AND METHODS: Two patients with refractory rheumatoid arthritis, who were treated on five occasions with the SPA column (as a part of a national trial) primed with 5000 U of heparin, were monitored for aPTT and heparin in their plasma. In addition, two in vitro analyses were performed with FFP for heparin elution from the SPA column. RESULTS: The in vivo studies showed the presence of 0.3 to 1.5 U per mL of heparin in patients' plasma at the end of the SPA column treatments that corresponded with the prolonged aPTTs. The in vitro studies showed that 82 to 85 percent heparin (approx. 4400 U) was eluted from the SPA column during rather than before the procedure. CONCLUSION: Patients undergoing SPA column treatments, especially those with thrombocytopenia, may be at increased risk of bleeding as a result of the presence of a significant amount of heparin in their circulation during the entire period of SPA column treatment.

Anticoagulants↗

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↗

The cost-effectiveness of autologous transfusion revisited: implications of an increased risk of bacterial infection with allogeneic transfusion.

BACKGROUND: Previous analyses have found autologous transfusion to be very expensive but have not considered avoidance of postoperative bacterial infections as one of its benefits. STUDY DESIGN AND METHODS: A cost-utility analysis using a Markov cohort simulation model compared autologous blood transfusion to allogeneic transfusion in a hypothetical cohort of patients undergoing elective total hip replacement with respect to discounted quality-adjusted life years (QALYs) and health-care system costs. RESULTS: Assuming a base case rate of serious infection of 3.7 percent, a relative risk of infection of 1.85, and additional costs of $12,980 per infection, autologous transfusion has a cost-effectiveness of $2,470 per QALY. If the relative risk of bacterial infection following allogeneic transfusion exceeds 1.1, the cost-effectiveness of autologous transfusion is less than $50,000 per QALY and if the relative risk exceeds 2.4, autologous transfusion is dominant, resulting in both lower costs and greater QALYs. If there were no increased risk of transfusion, the cost-effectiveness of autologous transfusion would be $3,400,000 per QALY. CONCLUSIONS: If there is only a modest increase in the risk of bacterial infection following allogeneic transfusion, autologous transfusion would result in improved outcomes at a cost of less than $50,000 per QALY. Autologous transfusion would be dominant above a relative risk of infection that is within the range of values observed in randomized controlled trials. However, if there is no increased risk of bacterial infection, autologous transfusion would be a very expensive strategy. Until more definitive data are available on the magnitude and costs of this risk, we advise against prematurely closing the debate about the cost-effectiveness of autologous transfusion.

Adult↗

Correlation of cytokine elaboration with mononuclear cell adhesion to platelet storage bag plastic polymers: a pilot study.

The basis for many febrile nonhemolytic transfusion reactions associated with platelet transfusion therapy is cytokine elaboration and accumulation in the storage bag, which correlate with the leukocyte content and the length of platelet storage. We propose that a possible additional variable in the elaboration and accumulation of cytokines is the differential adhesion of mononuclear cells to the plastic substrate of the platelet storage bag. We hypothesize that mononuclear cell adhesion-induced cytokine release is greater in random-donor platelet bags composed of the polyolefin polymer compared to the single-donor apheresis platelet bags composed of the polyvinyl chloride polymer with the tri-(2-ethylhexyl) trimellitate (TEHTM) plasticizer. For four blood donors, we demonstrate preferential mononuclear cell adhesion, in vitro, to discs of polyolefin polymer versus discs of polyvinyl chloride polymer with the TEHTM plasticizer. Scanning electron microscopy corroborates this. In addition, proinflammatory cytokine (interleukin 1beta [IL-1beta] and tumor necrosis factor alpha [TNF-alpha]) levels are greater in culture wells containing discs of polyolefin polymer than in those containing discs of polyvinyl chloride polymer with the TEHTM plasticizer, and even more so in storage bags containing polyolefin polymer versus polyvinyl chloride polymer with the TEHTM plasticizer (IL-1beta, TNF-alpha, IL-6, and IL-8). This study suggests, for the first time, that differential plastic substrate mononuclear cell adhesion may contribute to cytokine release during platelet storage. This may represent an additional variable in the pathophysiology of febrile nonhemolytic transfusion reactions in patients receiving stored platelet units.

Blood Platelets↗

Prolonged isolated thrombocytopenia after hematopoietic stem cell transplantation: morphologic correlation.

Prolonged isolated thrombocytopenia, defined as recovery of other cell counts with continuous dependence on platelet transfusions for greater than 90 days after hematopoietic stem cell transplantation (HSCT), develops in approximately 5% of patients who undergo HSCT. Although the clinical conditions associated with prolonged isolated thrombocytopenia have been studied, a systematic review of bone marrow biopsies has not been performed and the pathophysiologic basis has not been defined. We reviewed all HSCT at one center from 1990 to 1995 (n = 454) and found 12 cases that met criteria for prolonged isolated thrombocytopenia (incidence = 12/454 or 3%). Bone marrow core biopsies from 12 patients with prolonged isolated thrombocytopenia were reviewed to determine cellularity, numbers of megakaryocytes, the presence of atypical forms, and clusters of megakaryocytes. These marrow megakaryocyte counts were compared to age and disease matched controls, and 11 normal donors. Patients (aged 1-56 years, mean 32 years) who underwent HSCT (four sibling HLA-identical, five autologous bone marrow, three autologous peripheral stem cell) with prolonged isolated thrombocytopenia had a statistically significant lower absolute megakaryocyte count in bone marrow biopsies performed before transplantation and more than 30 days after transplantation compared to control patients (aged 4 months to 50 years, mean 31 years) who underwent HSCT (four sibling HLA-identical, four autologous bone marrow, four autologous peripheral stem cell) for similar conditions. No apparent differences were seen in size of megakaryocytes, nuclear-cytoplasmic ratios, or clustering of megakaryocytes. Overall marrow cellularities were similar in the three groups. These findings suggest that decreased differentiation of megakaryocytes from stem cells, rather than ineffective platelet production or peripheral destruction of platelets, causes prolonged isolated thrombocytopenia in HSCT patients. Low megakaryocyte counts prior to HSCT may be a useful prognostic indicator, as this feature was associated with the development of prolonged isolated thrombocytopenia.

Adolescent↗

Practical aspects of preoperative autologous transfusion.

Autologous transfusion, which is widely endorsed as the safest transfusion practice, has undergone rapid-and often unchecked-growth since the mid-1980s, primarily in response to the recognition of transfusion-associated HIV. Substantial improvements in blood transfusion safety, combined with the increasing emergence of managed care during the past decade, have spurred a reexamination of autologous transfusion and its ability to provide increased transfusion safety in a cost-effective manner. The ultimate utility of preoperative autologous donation and transfusion depends on whether (1) waste is limited by the development of meticulously crafted benchmarks for appropriate surgical applications, (2) donor-patient risk is limited by careful donor selection and scheduling and scrupulous attention to iron supplementation, (3) strategies are identified to enhance cost-effectiveness, and (4) policies and procedures are developed to reduce or prevent accidents and errors.

Bacterial Infections↗