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Biomedical subjects

M E Brecher

Publications and source records attributed to M E Brecher.

At least 55 records · Page 3Linked to original sources
PubMed1998

Thrombotic thrombocytopenic purpura that is refractory to therapeutic plasma exchange in two patients with occult infection.

BACKGROUND: The etiology of thrombotic thrombocytopenic purpura (TTP) remains undetermined. TTP has been associated with a number of secondary causes including infections, drugs, menses, pregnancy, autoimmune diseases, and bone marrow transplantation. Regardless of the inciting factors, it is widely accepted that endothelial injury and platelet aggregation are integral components. The morbidity and mortality have been significantly reduced with the use of plasmapheresis. However, refractory forms of TTP remain a clinical management challenge. Refractory TTP has not previously been associated with occult bacterial infection. CASE REPORT: Two patients had classic TTP that was refractory to daily plasma exchange with fresh-frozen plasma. Multiple attempts over a period of months to wean these patients off plasma exchange resulted in exacerbations of disease activity, as indicated by increased schistocytosis, decreased hematocrit, increased serum lactate dehydrogenase, and decreased platelet counts. Both patients were empirically treated for infections during hospitalization, although microbial cultures failed to isolate an organism. Discontinuation of antimicrobial therapy on multiple occasions in one patient was associated with recurrence of disease. In the other patient, dental extraction with drainage of an occult periodontal abscess resulted in sustained remission of disease. CONCLUSION: Occult bacterial infection may play a role in triggering and sustaining TTP that is refractory to conventional treatment. A careful search for such an infection and appropriate antimicrobial therapy should be considered in the management of these patients.

Anti-Bacterial Agents↗
PubMed1998

Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion-dependent patient.

BACKGROUND: It is known that in vivo platelet survival varies as the platelet count changes. Previous attempts at curve fitting fail to predict the decreased platelet survival in thrombocythemia. Therefore, mathematical relations that more closely approximate platelet survival were derived and used in models of platelet transfusion practice. STUDY DESIGN AND METHODS: A differential equation for platelet loss was derived that included a constant (constant homeostatic loss), a first-order term (senescent loss), and a second-order term (one proportional to the square of the platelet concentration and whose contribution is expected to be significant only at higher platelet concentrations). Data derived from this model was compared to platelet survival data in normal, thrombocytopenic, and thrombocythemic patients and to the platelet decay after high-dose chemotherapy. To provide further validation of this model, predicted and actual platelet requirements were calculated or obtained (chart review) in bone marrow patients with uncomplicated thrombocytopenia after ablation and at two platelet-transfusion thresholds (20 and 10 x 10(9)/L). RESULTS: The equations accurately modeled normal, thrombocytopenic, and thrombocythemic platelet survival. Chart review demonstrated a 12.5 percent reduction in platelet transfusion requirements when the transfusion threshold was reduced from 20 to 10 x 10(9) per L. The model predicted a reduction of 14.0 percent. For 100 days of uncomplicated thrombocytopenia and a transfusion threshold of 10 x 10(9) per L, transfusion of 3 units of platelet concentrates compared to a 6-unit pool of platelet concentrates, resulted in a 22-percent savings of platelet units. CONCLUSION: Platelet survival as a function of platelet concentration can be modeled by use of a differential equation. This model challenges current dogma regarding platelet destruction and predicts decreased platelet survival in thrombocythemic patients. The model illustrates that large doses of platelets would result in greater time between transfusions, however, more units of platelets are used. Consideration should be given to the more frequent use of smaller doses of platelets in patients who chronically require platelet transfusion support.

Cell Survival↗
PubMed1998

Lack of efficacy for conventional gamma irradiation of platelet concentrates to abrogate bacterial growth.

The maximum storage time for platelet concentrates is 5 days, owing to the higher risk bacterial contamination with longer storage. The expiration date could potentially be extended if a rapid system to detect microbial contamination or a safe sterilization technique could be developed and easily implemented. Gamma irradiation has decreased bacterial contamination in food products. Conventional doses of gamma irradiation were tested for their efficacy in decreasing bacterial growth during the 5-day platelet shelf life. An initial pilot study determined that bacteria suspended in normal saline at concentrations of 1 to 2 x 10(7) colony-forming units per milliliter showed a dose-related susceptibility to gamma irradiation. Subsequently, four platelet concentrates were pooled, inoculated with a known concentration of Staphylococcus autreus or Serratia marcescens, and divided. The concentrates were exposed to varying amounts of gamma irradiation, ie, no irradiation (control), 25, 50, and 75 Gy, and subjected to typical blood bank storage conditions. The platelet concentrates were sampled daily for 7 consecutive days to monitor bacterial growth by quantitative cultures. An inverse linear dose-related extinction of bacteria was evident in the pilot study with an extrapolated total kill in the 100 to 150 Gy range. There is no difference in bacterial growth with S aureus using irradiation levels from 0 to 75 Gy. A 1-day delay in bacterial growth at 75 Gy was found with S marcescens compared with units irradiated with 0 through 50 Gy. Exposure of bacteria-contaminated platelet concentrates on storage day zero to gamma irradiation at levels up to 75 Gy is ineffective at sterilizing the platelet concentrates. Higher levels of irradiation may be effective in sterilizing platelet concentrates. Function, survival, and sterility after higher than conventional levels of irradiation need further study.

Bacteria↗
PubMed1998

Autologous blood transfusion.

Autologous blood transfusion is an endorsed blood conservation strategy that has become widely practiced in elective surgical procedures. We review ten years' experience in this arena, along with emerging strategies designed to continue to minimize allogeneic blood exposure but reduce the costs associated with autologous blood procurement. We conclude that point-of-care autologous blood procurement (acute normovolemic hemodilution and intraoperative autologous blood salvage) can replace the predonation of autologous blood in surgical patients when transfusion medicine specialists, anesthesiologists, and surgeons develop a prospective, comprehensive approach to blood conservation.

Blood Banks↗
PubMed1997

A method for the production of CD4+ chronic myelogenous leukemia-specific allogeneic T lymphocytes.

The graft-versus-leukemia effect is critical to the maintenance of remission in patients transplanted for the treatment of chronic myelogenous leukemia (CML). A pivotal issue in transplantation for CML is whether donor lymphocytes are specific for host tumor or myeloid cells or a subset of the lymphocytes that cause graft-versus-host disease. We have enrolled seven patients in an experimental trial to evaluate the specificity of HLA-matched donor lymphocytes in vitro. We have produced 11 CD4+ cytotoxic and proliferative T-cell clones from five of the donors that only lyse or proliferate to leukemic myeloid cells. These T lymphocytes do not react with interleukin (IL)-2-stimulated blasts, natural killer-sensitive targets, donor neutrophils, or bcr-abl+ EBV-lymphoblastoid cell lines. We show that the addition of the cytokines IL-7 and IL-12 during the production of T-cell clones enhances the recovery of myeloid-specific clones in vitro. Five of the myeloid-specific clones that we produced maintained specificity over 12 weeks in culture. Adoption of this method should allow for the expansion and in vivo testing of CML-specific CD4+ T-cell clones in adoptive immunotherapy.

Adult↗
PubMed1997

Partial colloid starch replacement for therapeutic plasma exchange.

Traditionally protein solutions have been used as the replacement solution of choice during therapeutic plasma exchange (TPE). Treatment protocols vary, but neurology patients, who exhibit autonomic instability, are typically replaced entirely with 5% protein solution. Due to sporadic product shortages and the increasing cost of protein solutions, we evaluated the use of 6% and 3% hetastarch (HES) as partial replacement during TPE. All adult neurology patients with normal liver, heart, and kidney function were evaluated for HES replacement. The first seven patients (33 procedures) received 1000 ml of 6% hetastarch as part of their replacement fluid and the next 42 patients (289 procedures) received 1000 ml of 3% HES as part of their replacement fluid. Three patients crossed over into both groups. Patients were evaluated for signs of peripheral edema, evidence of bleeding, skin rash, and any subjective changes. Total protein albumin, osmolality, PT, and aPTT were measured prior to each procedure in the first five patients in each group. In both groups there was a drop in total protein, but all other lab values returned to normal limits within 48 hours of treatment. One patient reported slight peripheral edema after two procedures. In the 3% HES group the BP and P remained stable in 97.3% (280) procedures. Two patients receiving 6% HES and 1 patient receiving 3% HES complained of severe transient back and head pain during HES infusion. There was no evidence of bleeding or subjective changes. Three percent HES is a safe and cost-effective partial replacement for albumin during TPE.

Adult↗
PubMed1997

Alternatives to albumin: starch replacement for plasma exchange.

Today, albumin, or a combination of saline and albumin, is used and widely accepted as a replacement for routine plasma exchange. However, decreased availability (due to market recalls secondary to Creutzfeld-Jacob or bacterial contamination risk) rising costs, recognition of drug interactions with albumin (i.e., ACE inhibitors) and a fear of disease transmission have led several groups to reconsider the use of colloid starches as partial or full replacement for plasma during plasma exchange. There are two hydroxyethyl starches: hetastarch (Hespan and Pentaspan) currently licensed for human use in the United States. While both are approved for granulocyte collection only Hespan is approved as a plasma volume expander. Anecdotal experience and limited reports in the literature with the use of starches as a replacement for plasma exchange suggest that such starch products are a reasonable replacement for albumin as an initial wash-out fluid or in combination with either albumin or saline. Kinetic modeling of the wash-out of starch used as a replacement fluid demonstrate that relatively little residual starch remains compared to the total amount infused. Hydroxyethyl starches are biochemically similar to glycogen, which likely explains the lack of immunogenicity and lack of adverse reactions. Substantial cost savings are associated with the substitution of starch for albumin. It is concluded that HES is well-tolerated and cost-effective as full or partial volume replacement with plasma exchange. It is anticipated that the use of HES will emerge as a standard of care in apheresis.

Albumins↗
PubMed1997

Long-term engraftment failure after marrow ablation and autologous hematopoietic reconstitution: differences between peripheral blood stem cell and bone marrow recipients.

We infused peripheral blood stem cells (PBSC) into 51 patients with various malignant disorders, after myeloablative conditioning. Twenty-four patients also received autologous bone marrow (PBSC + BM). In a multivariate analysis, the only statistically significant predictors of neutrophil engraftment were log-dose CFU-GM (P < 0.001) and the number of prior chemotherapy regimens (P = 0.004). The factors predicting RBC and platelet engraftment were log-dose CFU-GM (P = 0.002), PBSC + BM infusion (P = 0.007) and the absence of neoplastic bone marrow involvement (P = 0.009). Seven patients remained platelet and/or red cell transfusion-dependent for 100 days or more post-transplant after good neutrophil recovery. Six of these seven long-term engraftment failures, as well as five additional patients, received < 10(5) CFU-GM/kg. Of the 11 patients who received < 10(5) CFU-GM/kg (low-dose patients), seven were PBSC recipients, of whom six were long-term engraftment failures. In contrast, there were no long-term engraftment failures among the four low-dose autologous marrow recipients. This difference in long-term engraftment failure rate was significant (P = 0.015). The low-dose PBSC patients all had a diagnosis of lymphoma with bone marrow involvement. The low-dose PBSC + BM group was more heterogeneous, but no patient had malignant involvement of the marrow. The low-dose PBSC patients had also received significantly more prior chemotherapy regimens than the low-dose PBSC + BM patients and a significantly higher proportion received total body irradiation (TBI) as part of their conditioning regimen. We conclude that marrow damage resulting from a combination of neoplastic infiltration, chemotherapy and TBI may result not only in low PBSC yields but also in an impaired capacity of the marrow microenvironment to support transplanted stem cells.

Adult↗
PubMed1997

A standardized method for calculating blood loss.

BACKGROUND: The estimation of blood loss for a surgical procedure is both poorly reproducible and typically underestimated. Therefore, comparison of surgical transfusion outcomes such as blood loss and amount of blood transfused from one institution to another, or from one surgeon to another, is difficult. Recently, mathematical modeling has contributed to our understanding of transfusion strategies. STUDY DESIGN AND METHODS: A mathematical model of blood loss for a surgical hospitalization was developed on the basis of recently described mathematical principles for blood loss and hemodilution. The model was designed so that the calculation of blood loss would be based on easily measured factors such as the patient's blood volume, the number and type of red cell units transfused, the initial hematocrit, the discharge hematocrit, the transfusion trigger, the volume of intraoperatively salvaged blood transfused, and the amount of hemodilution performed. The calculated blood loss was then compared with the intraoperative blood loss actually estimated by the anesthesiologist in 250 consecutive patients who underwent radical retropubic prostatectomy. RESULTS: The mathematical equations were placed in a computer model to allow rapid calculation of a particular patient's blood loss. Figures were derived from the computer modelling to facilitate rapid manual calculation of the blood loss. There was a significant relation (p < 0.001) between the calculated blood loss for the hospitalization and the estimated intraoperative blood loss. However, the calculated blood loss was on average 2.1 times the intraoperative blood loss estimated by the anesthesiologist. CONCLUSION: The use of such mathematical modeling to rapidly estimate a patient's blood loss has the potential to allow ready, objective comparisons between sites and even surgeons. It also allows for a more judicial and informed decision as to what (if any) blood should be available or what blood-conservation techniques should be employed for a specific patient.

Blood Loss, Surgical↗
PubMed1997

Rapid identification of bacterially contaminated platelets using reagent strips: glucose and pH analysis as markers of bacterial metabolism.

BACKGROUND: One in every 1000 units of platelets is bacterially contaminated, which puts patients at risk for transfusion-associated sepsis and death. However, there is currently no screening test in place to detect contaminated units. The use of commercially available multiple-reagent urine dipsticks for this purpose was evaluated. STUDY DESIGN AND METHODS: Platelet concentrates were inoculated with either sterile saline or suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Klebsiella pneumoniae, or Serratia marcescens to a final concentration of 50 colony-forming units (CFU) per mL. The platelets were analyzed daily by the use of multiple-reagent strips, quantitative culture, and glucometry. RESULTS: B cereus grew rapidly, reaching 10(7) CFU per mL 1 day after inoculation, while S. epidermidis grew slowly, achieving similar concentration 4 to 6 days after inoculation. Two of 10 dipstick reagents, glucose and pH, proved useful in detecting bacteria. Both were lower in bacterially contaminated units than in controls. Glucose data obtained from automated analyzers validated the dipstick data. All organisms were detected at concentrations > or = 10(7) CFU per mL, and S. aureus and K. pneumoniae were detected in the range of 10(3) to 10(5) CFU per mL. CONCLUSION: The multiple-reagent test used had a sensitivity and specificity of 95 percent (> or = 10(7) CFU/mL) and 98 to 100 percent, respectively. These data indicate that urine dipsticks can be used to rapidly and inexpensively detect bacterial contamination in platelet concentrates, which potentially will reduce morbidity and mortality at minimal cost.

Bacillus cereus↗
PubMed1997

Enumeration of CD34-positive stem cells: evaluation and comparison of three methods.

Accurate enumeration of CD34+ stem cells is important in assessing the need for continued mobilization and subsequent apheresis collections. We compared two new analysis systems, ProCOUNT (Becton Dickinson Immunocytometry Systems) and IMAGN 2000 STELLer (Biometric Imaging, Inc.) with our current (3-Color) flow cytometry-based method. The ProCOUNT system uses an absolute counting tube, which contains reference beads and a specific (multiple) gating strategy to determine an absolute count. The STELLer assay combines microvolume fluorimetry and automated analysis software to determine an absolute count. To evaluate linearity and reproducibility, peripheral blood was spiked with CD34+ cells (KG1a cell line). Three dilution series (measured at approximately equal to 0, 5, 10, 25, 50, and 100 CD34+ cells/microliter) were analyzed by each method. Analysis of predicted versus actual CD34+ concentration showed excellent correlation with all methods (r2 > or = 0.97, slope 0.98-1.04). To further assess precision, two PBSC samples, at approximately 200 and 800 CD34+ cells/microliter, respectively, were analyzed 10 times by each method. Coefficients of variation for the precision analysis of these samples were 5.1%-6.4% and 5.4%-12.3%, respectively. To assess overall performance, 75 patient specimens were analyzed. Excellent correlation (r2 values of 0.89-0.98) was observed among all three methods. We conclude that the three methods provide comparable linearity and reproducibility.

Antigens, CD34↗
PubMed1997

Acute normovolemic hemodilution can replace preoperative autologous blood donation as a standard of care for autologous blood procurement in radical prostatectomy.

UNLABELLED: Predonation of autologous blood (PAD) is a standard of care for patients undergoing radical prostatectomy, but recent studies have shown that PAD is not cost-effective. Acute normovolemic hemodilution (ANH) is an alternative autologous blood procurement technique that is much less costly than PAD. We compared the efficacy and costs of ANH alone to ANH combined with PAD. Two hundred-fifty patients who predonated fewer than 3 units of autologous blood before radical prostatectomy underwent ANH to a target hematocrit of 28%. Perioperative hematocrit levels, transfusion outcomes and costs, and postoperative outcomes were compared for patients who predonated 0, 1, or 2 units of blood before surgery. A computer model was used to estimate the savings in red blood cells (RBC) associated with each autologous intervention. ANH alone resulted in a 21% allogeneic transfusion rate and contributed a mean net savings of 112 mL RBC in blood conservation (equivalent to 0.6 unit of blood). The addition of 1 or 2 units of PAD reduced allogeneic exposure rates to 6% or 0%, respectively. Overall, patients who predonated blood had a mean net loss of 198 mL of RBC (equivalent to 1 blood unit), due to both an absence in compensatory erythropoiesis and to the wastage of 60% of the blood units donated. Patients who underwent ANH alone had a 60% reduction in mean total transfusion costs ($103 +/- $102) compared with patients who predeposited 2 units of autologous blood in addition to ANH ($269 +/- $11, P < 0.05). We conclude that ANH can replace PAD as an autologous blood option because it is less costly and equally effective. A combination of ANH and PAD can further decrease allogeneic blood exposure, but it increases transfusion costs and wastage. IMPLICATIONS: A patient's own blood can be obtained for use in surgery by predonation or acute normovolemic hemodilution on the day of surgery. Both blood collection techniques decrease the need for blood bank transfusions, but acute normovolemic hemodilution is less expensive and more convenient for patients.

Aged↗
PubMed1996

Washout kinetics of colloidal starch as a partial or full replacement for plasma exchange.

Colloidal starch has been used safely as a plasma expander and an erythrocyte sedimenting agent for over 25 years. However, there remains some concern in regard to the long term sequelae of the administration of large volumes of colloid starch such as would be administered if colloidal starch were used as a plasma replacement during serial plasma exchanges. We identified mathematical relations that allowed for the calculations of the theoretical circulating residual starch in a patient undergoing serial plasma exchanges and used it to model a variety of possible clinical scenarios. Following six one plasma volume exchanges, one would expect only 11, 13, 14, or 17% of the total infused starch to be remaining in the circulation. For example, in the case of a 4L exchange with full replacement, only the starch in 4.1 liters (4L x 6 exchanges x 17% = 4.1L) would be expected to remain in the circulation despite an infusion of 24 L (4L x 6 exchanges = 24L) of starch. The results suggest that relatively small amounts of starch would be expected to remain circulating relative to the large amounts infused following a series of plasma exchanges with partial or full starch replacement.

Colloids↗
PubMed1996

Autologous blood procurement in the surgical setting: lessons learned in the last 10 years.

The percentage of blood transfused yearly that is autologous has increased substantially over the last 10 years. While autologous blood is regarded as a standard of care in many elective surgical settings, the increasing safety of allogeneic blood and the expense of autologous blood procurement have raised question regarding the appropriate roles of autologous blood in blood conservation strategies. We therefore review current activities and emerging questions that arise from this maturing arena.

Blood Donors↗