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Lorna M. Williamson

Bio: Lorna M. Williamson is an academic researcher from NHS Blood and Transplant. The author has contributed to research in topics: Blood transfusion & Fresh frozen plasma. The author has an hindex of 39, co-authored 113 publications receiving 7284 citations. Previous affiliations of Lorna M. Williamson include University College London & University of Cambridge.


Papers
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Journal ArticleDOI
TL;DR: Fresh‐frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited and should not be used to reverse warfarin anticoagulation in the absence of severe bleeding, and PRP may be used as an alternative to FFP.
Abstract: The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.

786 citations

Journal ArticleDOI
TL;DR: The aim is to engineer non‐destructive human IgG constant regions for therapeutic applications where depletion of cells bearing the target antigen is undesirable and a lack of killing via Fcγ receptors (R) and complement but retention of neonatal FcR binding to maintain placental transport and the prolonged half‐life of IgG.
Abstract: Subclasses of human IgG have a range of activity levels with different effector systems but each triggers at least one mechanism of cell destruction. We are aiming to engineer non-destructive human IgG constant regions for therapeutic applications where depletion of cells bearing the target antigen is undesirable. The attributes required are a lack of killing via Fcgamma receptors (R) and complement but retention of neonatal FcR binding to maintain placental transport and the prolonged half-life of IgG. Eight variants of human IgG constant regions were made with anti-RhD and CD52 specificities. The mutations, in one or two key regions of the CH2 domain, were restricted to incorporation of motifs from other subclasses to minimize potential immunogenicity. IgG2 residues at positions 233 - 236, substituted into IgG1 and IgG4, reduced binding to FcgammaRI by 10(4)-fold and eliminated the human monocyte response to antibody-sensitized red blood cells, resulting in antibodies which blocked the functions of active antibodies. If glycine 236, which is deleted in IgG2, was restored to the IgG1 and IgG4 mutants, low levels of activity were observed. Introduction of the IgG4 residues at positions 327, 330 and 331 of IgG1 and IgG2 had no effect on FcgammaRI binding but caused a small decrease in monocyte triggering.

467 citations

Patent
07 May 1999
TL;DR: In this paper, the authors defined a class of binding molecules which are recombinant polypeptides comprising: (i) a binding domain capable of binding a target molecule, and (ii) an effector domain having an amino acid sequence substantially homologous to all or part of a constant domain of a human immunoglobulin heavy chain.
Abstract: Disclosed are binding molecules which are recombinant polypeptides comprising: (i) a binding domain capable of binding a target molecule, and (ii) an effector domain having an amino acid sequence substantially homologous to all or part of a constant domain of a human immunoglobulin heavy chain; characterised in that the binding molecule is capable of binding the target molecule without triggering significant complement dependent lysis, or cell mediated destruction of the target, and more preferably wherein the effector domain is capable of specifically binding FcRn and/or FcηRIIb. These are generally based on chimeric domains which are derived from two or more human immunoglobulin heavy chain CH2 domains. In preferred embodiments the regions 233-236, and 327-331, are modified, as are further residues to render the molecule null allotypic. The binding domain may derive from any source appropriate to the (usually clinical) application for the molecule and may be from e.g. an antibody; an enzyme; a hormone; a receptor; a cytokine or an antigen; a ligand and an adhesion molecule. Also disclosed are nucleic acids, host cells, production processes and materials, and uses e.g. to inhibit B cell activation; mast cell degranulation; phagocytosis, or to inhibit the binding of a second binding molecule to the target molecule. Pharmaceutical preparations are also disclosed.

465 citations

Journal ArticleDOI
01 Oct 1998-Blood
TL;DR: Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32, but was not observed in babies of women of women with either transient or postnatal-only antibodies.

417 citations

Journal ArticleDOI
TL;DR: !!( ) + ( $# &, $$ ,( ! " ) & & -$) $, $ ! $ $ $# + " & $! &!$ . $ / !0 & ! " $ $ " " " $ & +! " $ " #$! & ! “ 0 "+ !$ " +! / $ " -+ " & ##$!$# ) " & )!
Abstract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

388 citations


Cited by
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Journal ArticleDOI
TL;DR: Antibody-dependent cellular cytot toxicity assays using purified peripheral blood monocytes or natural killer cells from several donors showed enhanced cytotoxicity, especially evident at lower antibody concentrations.

2,107 citations

Journal ArticleDOI
TL;DR: IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review.
Abstract: Of the five immunoglobulin isotypes, Immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3 and IgG4 which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptor (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or Antibody-dependent cell-mediated cytotoxicity (ADCC), and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc-receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function, will be the focus of the current review.

1,834 citations

Journal ArticleDOI
TL;DR: Select IgG1 variants with improved binding to FcγRIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fcγ RIIIA co-crystal structure.

1,788 citations

Journal ArticleDOI
TL;DR: These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections.
Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

1,733 citations

Journal ArticleDOI
TL;DR: The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.
Abstract: The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

1,691 citations