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Biomedical subjects

L M Williamson

Publications and source records attributed to L M Williamson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Leucodepletion of blood products by filtration.

The leucocytes present in red cell and platelet components have been implicated in several important immunological and infective complications of blood transfusion. Recent developments in blood filtration technology allow the production of leucodepleted blood products (residual leucocytes < 5 x 10(6) per transfused unit) in the laboratory or at the bedside with the potential to prevent these adverse effects. Quality assurance remains an important problem, particularly for bedside filtration. Prestorage filtration may have significant advantages for red cell and platelet production. There is strong clinical evidence that 3 log10 leucodepletion prevents or delays febrile reactions in patients receiving multiple red cell transfusions and can reduce cytomegalovirus transmission. Leucodepletion to prevent HLA alloimmunisation, platelet refractoriness and febrile reactions in patients receiving red cell and platelet support remains controversial. Transfused leucocytes induce 'immunosuppressive' changes in the recipient, but recent studies cast doubt on the association with cancer recurrence after surgery. However, leucodepleted blood may reduce the incidence of postoperative infection. Leucodepletion by filtration is expensive and there is a requirement for well-designed prospective clinical studies focusing on appropriate filtration technology (and alternatives), clinical outcome and cost-effectiveness.

Animals↗
PubMed1995

Transfusion-associated graft-versus-host disease and its prevention.

Transfusion-associated graft-versus-host disease is a rare but usually fatal complication of transfusion of cellular blood components, caused by multiorgan engraftment and proliferation of donor T lymphocytes. The classical features of skin rash, diarrhoea and hepatitis, along with striking bone-marrow failure, are seen 1-2 weeks after transfusion. Although early reports described the condition only in immunosuppressed individuals, sharing of an HLA haplotype between donor and an immunocompetent recipient can also result in transfusion-associated graft-versus-host disease. The condition is entirely preventable by gamma irradiation of cellular blood components to 25 Gy, although this results in some reduction of red-cell viability and increased loss of red-cell potassium. The major indications for irradiated blood components include bone marrow/stem cell auto- or allografting, Hodgkin's disease, intrauterine transfusions, and transfusions from relatives or HLA-selected platelet donors.

Blood Donors↗
PubMed1995

Feasibility and usefulness of an efficient anti-HBc screening programme in blood donors.

Post-transfusion hepatitis B remains a risk for recipients of hepatitis B surface antigen (HBsAg) screened blood. Anti-hepatitis B core antibody (anti-HBc) screening may help reduce this risk. To evaluate its usefulness, 9,238 East Anglian blood donors were screened for anti-HBc. Those with isolated anti-HBc were identified with two confirmatory anti-HBc and anti-HB surface antibody (anti-HBs) assays. The prevalence of anti-HBc reactions in screening and confirmatory assays was 1.29% and 0.35%, respectively. The level of reactivity was significantly higher when two anti-HBc assays gave concordant results or, being concordant, were anti-HBs positive. All isolated anti-HBc-positive units (0.04%) were negative for additional HBV markers including DNA tested with nested polymerase chain reaction (PCR). A 0.31% prevalence of past HBV infection was found in this population, all carrying both anti-HBc and anti-HBs antibody, most above the protective level (0.1 IU/ml). The proposed screening schemes would limit the number of deferred donors and discarded units and keep the testing time within the remit of routine blood banking practices for an additional cost of approximately 1 pound per unit. However, no evidence was found in this donor population to suggest that anti-HBc screening would significantly reduce the incidence of post-transfusion hepatitis B.

Blood Donors↗
PubMed1995

Virally inactivated fresh frozen plasma.

Several technologies are now available to treat whole fresh-frozen plasma (FFP) to inactivate transfusion-transmitted viruses, including pasteurisation, solvent/detergent and methylene blue/light. The first two involve creating large plasma pools prior to inactivation, while only pasteurisation clearly destroys both enveloped and non-enveloped viruses. Some of the issues surrounding the use of these products include demonstration of both clinical efficacy and improved viral safety, and the need for product licencing. Potential benefits must be balanced against the risks of plasma pooling, while the increased costs will require comparison with other strategies such as quarantining of plasma. It is also recognised that reducing inappropriate FFP usage will play a role in improved patient safety.

Detergents↗
PubMed1994

Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group.

To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cells and platelets. Quality control of bedside filtration was explored by sequential sampling downstream of the filter, but this did not predict the total number of leucocytes transfused. After exclusions, 123 evaluable patients were assessed every two weeks until the end of therapy. HLA antibodies developed in 21 of 56 (37.5%) nonfilter (NF) and 15 of 67 (22%) filter (F) patients (risk ratio estimate, 0.60 [95% confidence interval, 0.34 to 1.05]; P = .07). Patients with acute myeloid leukemia (AML; n = 53) had higher alloimmunization rates in both arms of the study, with a greater effect of filtration (62.5% NF and 31.0% F; P = .025). Bedside filtration did not affect the overall incidence of febrile transfusion reactions (FTRs; 37% NF and 34% F; P = .71) or of platelet refractoriness assessed in 50 patients (30% NF and 26% F), despite an association between broad HLA reactivity and both FTRs and refractoriness. However, FTRs were also seen in 28 patients without HLA antibodies. Five alloimmunized refractory patients (2 F and 3 NF) required HLA-selected platelets. This report, the first prospective study of bedside filtration, has failed to show clear clinical benefit. Methodological limitations may account in part for this failure, notably the difficulties in accurately assessing the number of leucocytes transfused.

Adolescent↗
PubMed1994

Transient loss of proteins carrying Kell and Lutheran red cell antigens during consecutive relapses of autoimmune thrombocytopenia.

A patient is described in whom two consecutive relapses of autoimmune thrombocytopenic purpura (AITP) were associated with loss of red cell antigens of the Kell and Lutheran blood group systems respectively. During the second relapse the glycoprotein CD44 and to a lesser extent the LW antigen were also depressed. Both relapses were associated with concomitant production of IgG antibody recognizing high-frequency determinants on the corresponding antigen-carrying protein. Blocking of antigen sites by these antibodies was not the cause of reduced antigen expression, because immunoblotting studies showed absence of Kell protein during the first relapse, and Lutheran protein during the second. On both occasions the red cell changes reverted to normal with disappearance of the antibody as the AITP entered remission. There was no evidence of clonal lymphocyte expansion as demonstrated using immunoglobulin JH and T cell receptor beta chain probes.

Adult↗
PubMed1992

Clinical aspects of platelet transfusion.

Several clinical complications of platelet transfusions relate to contaminating donor leucocytes, and a number of strategies have been devised to leucodeplete platelet products before transfusion. Both alloimmunization to class I human leucocyte antigens (HLA), which causes febrile transfusion reactions and refractoriness to transfused platelets, and transmission of cytomegalovirus have been shown to be reduced by 3-log10 leucodepletion by filtration. Lesser degree of leucodepletion, e.g. by platelet preparation from buffy coats, will control febrile transfusion reactions, but will not reliably prevent other complications. The clinical implications and cost-effectiveness of different strategies of platelet production remain a matter of debate.

Blood Component Transfusion↗
PubMed1992

Molecular biology for platelet alloantigen typing.

Hitherto, full investigation of patients with alloimmunization to platelet-specific antigens has been difficult due to the limited availability of both typing reagents and panels of typed platelets. Following recent advances in the understanding of the molecular and genetic basis of platelet alloantigens, it is now possible to genotype individuals for the alleles coding for the epitopes of four platelet antigen systems (HPA-1-4). This is based on the finding that the two alleles differ by only a single base pair substitution, resulting in one amino acid difference in the relevant platelet glycoprotein. The technique involves amplification of the relevant segments of genomic DNA from any nucleated cell by the polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The technique allows investigation of thrombocytopenic individuals and fetuses/neonates, and can be readily applied to large-scale typing of platelet donors.

Alleles↗
PubMed1992

Program descriptions: a positive outcome from change.

1. Major organizational restructuring was the impetus for standardization of occupational health practice at three hospital sites. 2. A generic framework was devised to describe the key occupational health programs. 3. The process of developing these program descriptions yielded obvious quality assurance monitors. 4. Corporate change often is perceived as threatening. The development of a useful tool through cooperative team effort has produced a positive outcome.

Humans↗
PubMed1989

Blood usage for elective surgery. A reappraisal of the need for autologous transfusion.

To assess the need for a pre-operative autologous transfusion programme in a large teaching hospital, a review of blood cross-matching and transfusion practice for three elective surgical procedures was undertaken. For hysterectomy, the cross-match rate was 28%, and the transfusion rate only 8%. For transurethral resection of prostate and hemicolectomy, all patients were cross-matched, but only 19% and 36%, respectively, transfused. Given these figures, an autologous transfusion programme was not felt to be cost-effective. Local audit is necessary before this can be ascertained for a given district, as is consideration of the likelihood of infectious hazards in the regional blood supply.

Blood Grouping and Crossmatching↗
PubMed1988

Effect of feverfew on phagocytosis and killing of Candida guilliermondii by neutrophils.

The in vitro effect of the herbal remedy feverfew on neutrophil function was examined. It was shown that addition of feverfew extract inhibited phagocytosis of Candida guilliermondii and its overall killing. However, intracellular killing was not affected, suggesting that the apparent defect in total killing merely reflected the failure of uptake. The implications for the in vivo effects of feverfew are discussed.

Candida↗
PubMed1986

Neutrophils are involved in the increased vascular permeability produced by activated complement in man.

To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by removal of C5 from serum. Biopsy of a wheal revealed neutrophils adherent to vascular endothelium. In neutropenic subjects (neutrophil count less than 0.5 X 10(9)/l), responses to complement-activated serum or a low molecular weight fraction from it were significantly reduced. This could not be accounted for by a reduction in concentration of C5 conversion products. In one subject with chronic granulomatous disease a normal response was produced. Local injection of the anti-histamine (H1) drug clemastine produced only partial inhibition of responses, while almost totally abolishing histamine-induced wheals. Systemic anti-inflammatory drugs had no effect. The data suggest that the microvascular response to activated complement in man is at least partly due to an interaction between C5 fragments and neutrophils.

Adult↗