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Biomedical subjects

N Blumberg

Publications and source records attributed to N Blumberg.

At least 37 records · Page 2Linked to original sources

Allogeneic transfusion and infection: economic and clinical implications.

An increased incidence of postoperative infection and risk of cancer recurrence in patients who have received allogeneic blood transfusions suggests that such transfusions may be associated with clinically significant immunomodulatory effects. Allogeneic transfusion increase humoral immunity and decrease cell-mediated immunity. The mechanism of allogeneic transfusion-induced immunomodulation may involve altered cytokine regulation with a shift toward a type-2 (Th2) immune response. In patients undergoing hip replacement or spine surgery, the postoperative infection rate with allogeneic blood transfusion appears to be 7- to 10-fold higher than with autologous blood or no transfusion. The occurrence of postoperative infection is largely abrogated through the use of autologous or leukocyte-depleted blood. In our orthopedic surgery patients, use of allogeneic blood was associated with a significantly increased length of hospital stay, resource consumption, and attendant hospital charges. Allogeneic, but not autologous, blood transfusion were associated in a dose-dependent manner with longer hospital stays and higher costs. Multiple linear regression analyses demonstrated that the number of units of allogeneic blood transfused, rather than surgeon and type of surgery, was the most statistically significant predictor of length of stay and hospital charges. Using data reported in the literature, we estimate that the death rate from allogeneic transfusion-related postoperative infection and cancer recurrence combined (215 deaths with 1% causality to 21,500 with 100% causality) may exceed the death rate due to all other transfusion risks combined. Improved clinical outcomes may result from techniques that minimize allogeneic blood use or its immunologic effects (e.g., autologous transfusion or other blood-sparing approaches in surgery, leukodepletion of allogeneic blood, and the use of growth factors [eg, epoetin alfa]).

Blood Transfusion↗

A cost analysis of autologous and allogeneic transfusions in hip-replacement surgery.

PURPOSE: To analyze the cost consequences of autologous versus allogeneic transfusions. METHODS: Costs were determined when allogeneic transfusions were given in addition to, or instead of, autologous transfusions. Hospital charges were used to estimate costs for hip-replacement surgery. The main outcome measure was estimated incremental hospital costs per unit transfused. RESULTS: Among donors of autologous blood, mean total charges were $7,200 greater for recipients of both autologous and allogeneic transfusions than for recipients of autologous transfusion only (P=0.0001). Each allogeneic transfusion was associated with additional costs of $1,480. In a second cohort of patients receiving identical amounts of either allogeneic or autologous blood (mean=2.3 units), total hospital charges were a mean of $4,800 greater (P=0.0001) for allogeneic recipients. The per unit excess costs associated with each unit of allogeneic blood cohort were $1,043. CONCLUSIONS: Allogeneic transfusions are associated with incremental hospital costs of about $1,000 to $1,500 per unit transfused when compared with costs for similar patients receiving no transfusions or 1 to 5 units of autologous blood.

Analysis of Variance↗

Interaction of platelet fc and complement receptors with circulating immune complexes involving the AB0 system.

When platelets that are AB0-nonidentical are transfused, circulating immune complexes (CIC) are formed. In the present study we examined the ability of polyclonal antibodies to two C1q receptors on platelets, cC1q-R and gC1q-R, and a monoclonal IgG Fc gamma RII (CD32) antibody directed against the platelet Fc receptor to inhibit the uptake of CIC involving the AB0 blood group system by normal platelets. Four types of immune complexes of varying purity were made in vitro. In addition serum from 5 refractory group A patients who had demonstrable AB0 CIC, 5 patients who had received only AB0-identical platelets and had no AB0 CIC and 6 normal donors were evaluated. After exposure of normal platelets to serum of patients with demonstrable AB0 CIC there were increased levels of platelet-associated IgG. This binding was partially inhibited by preincubation of the platelets with either anti-cC1q-R (3/5 patients), gC1q-R (3/5 patients) or IgG Fc gamma RII in 4/5 patients. However, the pattern of inhibition by the three antibodies was variable. Using the artificial immune complexes a more consistent pattern was obtained. The binding of four types of artificial immune complexes to platelets was reduced by 67-99% after preincubation of the platelets with antibodies to the complement and Fc receptors. The present work supports the hypothesis that AB0 CIC bind to Fc and complement receptors on the platelet and if confirmed would suggest a pathophysiological mechanism for the clinical observations of the important role of AB0 in platelet transfusion.

ABO Blood-Group System↗

Current research on the immunomodulatory effect of allogeneic blood transfusion.

This review summarizes three aspects of current research on the immunomodulatory effect of allogeneic transfusion. Representatives of three laboratories-each of which is actively engaged in research on transfusion-induced immunomodulation-summarize their current investigative approach. First, current animal models of transfusion-induced immunomodulation are presented and research on the tumor growth-promoting effect of allogeneic transfusion is described. Second, mechanisms underlying an immunomodulatory effect of transfusion are summarized and experiments on the induction of transplant tolerance by selective introduction of donor-type MHC antigens is presented. Third, the potential clinical impact of increased infection and tumor recurrence resulting from transfusion-induced immunomodulation is assessed. The potential role of donor-derived hematopoietic stem cells is presented as an area of future investigation in the area of transfusion-induced immunomodulation.

Adoptive Transfer↗

The effect of low molecular weight heparin (fragmin) on myocardial neutrophil accumulation and infarct size in a rat model of myocardial infarction.

BACKGROUND: Heparin molecules possess immunomodulating properties, which are thought to complement their established antithrombotic activity. The purpose of this study was to evaluate whether the antiinflammatory properties of low molecular weight heparin (LMWH) can attenuate polymorphonuclear neutrophil accumulation and infarct size in a rat model of myocardial infarction. METHODS: Myocardial infarction was induced by ligating the left main coronary artery. LMWH (fragmin 500 anti-FXa u/kg) or vehicle (saline) were administered subcutaneously thirty minutes prior to coronary artery occlusion. Significant anticoagulant activity was attained with LMWH for more than eight hours. Twenty-four hours later, neutrophil accumulation and infarct size were determined by measuring left ventricular free wall myeloperoxidase and residual creatine kinase activity, respectively. RESULTS: As compared with rats administered vehicle, myeloperoxidase activity was insignificantly decreased in rats treated with LMWH (1.24 +/- 0.28 u/g vs 1.66 +/- 0.15 u/g, P = 0.16. Infarct size was also not significantly different between the groups (62.48 +/- 3.5% and 50.67 +/- 7.2% of left ventricular free wall with vehicle and LMWH, respectively, P = 0.1). CONCLUSION: The authors conclude that LMWH does not significantly reduce myocardial neutrophil accumulation and infarct size twenty-four hours after myocardial infarction in the rat.

Animals↗

Leukodepleted-ABO-identical blood components in the treatment of hematologic malignancies: a cost analysis.

To assess the effect of ABO-identical, filtration leukodepleted transfusions on resource consumption and costs of care we performed a cohort study in consecutive adult patients admitted for induction therapy of acute myeloid or lymphoid leukemia during 1985-92 (n = 120) and consecutive adult patients admitted for autologous bone marrow transplantation for Hodgkin's or non-Hodgkin's lymphoma during 1989-1991 in our university hospital. Patients with acute leukemia received either ABO unmatched, unfiltered transfusions (1985-89), ABO identical, unfiltered transfusions (1987-90), or ABO identical, filtered transfusions (1990-92). Patients with lymphoma received either ABO unmatched, unfiltered transfusions (1989-90) or ABO identical, filtered transfusions (1990-91). Mean platelet transfusion requirements per patient decreased with ABO identical platelets and filtered transfusions: from 143 to 71 units in the transplant setting; from 146 to 83 in acute leukemia (P < 0.05). Mean hospital ancillary service charges in 1992 dollars decreased with ABO identical platelets and filtered transfusions approximately $14,000 per patient for acute leukemia and $26,000 for for lymphoma. Per patient actual costs for filters ($643 in transplantation for lymphoma and $875 in leukemia) were offset by savings in actual blood component purchase costs alone ($4,127 in lymphoma and $3,283 in leukemia). In our setting, introduction of ABO identical platelets and filtration leukodepletion were implemented with substantial decreases in costs.

ABO Blood-Group System↗

A possible survival advantage in adults with acute leukemia receiving ABO-identical platelet transfusions.

In a small cohort of leukemic patients participating in a randomized trial of ABO-identical vs. ABO-unmatched platelet transfusions, a statistically significant decrease in remission duration and increase in mortality were observed in patients receiving ABO-unmatched platelet transfusions. This difference was unexplained by previously described prognostic factors for remission duration and survival. Further study of this association is warranted.

ABO Blood-Group System↗

Use of single donor platelets.

Advances in apheresis technology have made single donor platelets easier to obtain and therefore more plentiful. There are some hypothesized advantages to single donor platelets including reduced disease transmission, reduced alloimmunization, and superior function and storage characteristics. These ideas have swayed some to insist that single donor platelets should become the routine platelet transfusion component. While support exists for some of these benefits, there is no consensus that the risks to donors, the difficulties of setting up a program, and the expenses are sufficiently outweighed that the conversion of blood banks to a single donor platelet supply is merited. The major advantage to single donor platelets is that the selection of certain donor characteristics, such as HLA compatibility, is facilitated since a total dose of platelets is coming from one donor.

ABO Blood-Group System↗

Leukocyte-reduced transfusions of ABO-identical platelets and clinical outcome in autologous bone marrow transplantation for lymphoma.

In observational studies, use of ABO-identical platelets and leukocyte-reduced blood components have been associated with prolonged survival and reduced morbidity in acute leukemia. We present an analysis of the clinical results of instituting a policy of ABO-identical, leukoreduced transfusions in adult patients with lymphoma undergoing autologous bone marrow transplantation. Consecutive patients with Hodgkin's disease or non-Hodgkin's lymphoma were treated with a BEAC conditioning regimen. The use of ABO-identical platelets and leukoreduction of blood components was associated with reductions in mean number of days with fever > or = 38.5 degrees C (17 vs 10), number of days of antibiotics (34 vs 22) and numbers of days until recovery of neutrophil count > or = 500 x 10(6)/l (26 vs 18). Use of leukoreduced transfusions was the only statistically significant treatment factor predicting more rapid neutrophil engraftment. No significant difference in event-free or overall survival was observed. The differences in morbidity were not explained by variations in supportive care such as use of hematopoietic growth factors, use of peripheral blood stem cells or by any measures of pretransplant disease extent or severity. While conclusions based on cohort studies must be viewed conservatively, these data are consonant with observations from previous animal models and clinical studies. ABO-identical platelet transfusions and leuko-reduction are associated with reduced morbidity in patients undergoing autologous bone marrow transplantation for lymphoma.

ABO Blood-Group System↗