ARTICLE
platelet function tests such as light transmission aggregometry. However, WBA test results are affected by variables such as platelet count and von Willebrand factor activity, and may be influenced by haematocrit. There are currently several commercially available WBA assay platforms, including the VerifyNow (Accumetrics), Model 700 Aggregometer (Chronolog), PFA-100 (Siemens) and Multiplate (Roche Diagnostics) platforms. These utilise different approaches for specimen manipulation, test conditions and endpoint determination and express platelet function as different numerical output parameters, reflecting a composite of platelet adhesion and aggregation. The WBA technique has been applied successfully in several diagnostic settings including investigation of inherited platelet function and other primary haemostasis disorders, and in detection of heparin-induced thrombocytopenia. However, the VerifyNow and Multiplate platforms have been studied in greatest detail as tools to monitor the antiplatelet drugs aspirin and clopidogrel in patients undergoing interventional procedures for coronary artery disease. For example, in patients receiving clopidogrel after coronary stent insertion, high platelet reactivity to the ADP agonist on the Multiplate platform (indicating clopidogrel resistance) predicts stent thrombosis. In contrast, very low platelet reactivity to ADP (indicating clopidogrel hypersensitivity) predicts bleeding after coronary stent insertion and excessive blood loss and transfusion of blood components after cardiac surgery. The clinical impact of platelet testing by WBA has also been studied in a randomised, controlled trial in which patients receiving conventional-dose antiplatelet drugs after coronary stent insertion were switched to more intensive antiplatelet treatment if they displayed high residual platelet reactivity using the VerifyNow platform. In this setting, patients managed with WBA-guided antiplatelet drug regimens showed the same clinical outcomes compared to patients who were not tested by WBA, suggesting no benefit from testing. Platelet testing by WBA is a promising approach, particularly in monitoring antiplatelet drugs.
TRANSFUSION SCIENCE Transfusion management of haemoglobinopathies Haemoglobinopathies are the most common monogenic inherited mutations in the world. The mutations can cause a structural change in the haemoglobin molecule resulting in formation of a variant, or may result in a decrease or complete absence in production of the gene involved. The latter are known collectively as the thalassaemias. Patients with these conditions require life-long treatment and follow-up, so it is strongly recommended that they be placed under the care of a multidisciplinary team in a specialist
714 THE BIOMEDICAL SCIENTIST
centre. One of the most clinically important variant haemoglobins results in sickle cell disease and affected patients require blood transfusions to prevent vaso-occlusive crises; however, they are also prone to a hypercoagulable state, so maintaining a haemoglobin level of no more than 100 g/L is of paramount importance. Patients with sickle cell anaemia also suffer from spleen/liver sequestration, priapism and hyperhaemolysis. Patients with β-thalassaemia major have a complete absence of globin production and therefore require transfusions to correct the anaemia. It is important to ensure they are transfused efficiently in order to prevent extramedullary haematopoiesis and bone marrow expansion. The presentation also included an overview of the national guidelines and provided an insight into how the laboratory deals with individual patient needs.
Introducing the new IT guidelines for transfusion laboratories Since the British Committee for Standards in Haematology (BCSH) guidelines for the use of information technology (IT) in blood transfusion laboratories were published, there has been considerable development in IT applications available for use in transfusion medicine. IT has made a major contribution to blood safety throughout the transfusion chain by facilitating secure electronic data transfer within the laboratory and clinical areas. There is increasing use of IT solutions to allow laboratories to meet some of the challenges of the Blood Safety and Quality Regulations legislation, such as traceability. The revised guidelines update those published in 2007 to reflect these developments. The revised guidelines are intended to support hospital blood transfusion laboratories when changing laboratory information management systems (LIMS). These are at the centre of IT in these settings and while many IT systems are in use in transfusion medicine, from vein to vein, these guidelines address applications which
interface directly to the LIMS. Supporting ‘tracking’ applications are not covered in detail, but the interoperability with the LIMS is referenced where appropriate. Wherever possible, other BCSH transfusion guidelines are cross referenced to avoid duplication of information and the potential for inconsistency between guidelines. It is envisaged that this document will be used by transfusion laboratories, hospital IT departments and, where applicable, suppliers of IT systems that support hospital transfusion medicine.
In vitro production of platelets from human induced pluripotent cells by GMP-compatible methods Each year, a quarter of a million platelet concentrates are used in the UK, 15,000 of which are derived from human leucocyte antigen (HLA)-matched donors for patients refractory to standard products. Currently, a method is being developed for in vitro production under GMP standards of platelets from human induced pluripotent stem cells (iPSCs). The goal is to establish iPSCs cell banks from common haplotypes coupled with an efficient method of platelet production to cover 80% of matched platelet transfusion needs in the UK. A forward programming culture method is being developed based on the use of viral transduction of iPSCs to over-express transcription factors (TFs) central to megakaryopoiesis, coupled with the use of chemically defined media to grow mature megakaryocytes (MKs) from iPSCs. Megakaryocyte production was assessed using surface markers by flow cytometry at various time points of culture. Cell sorting experiments were performed to confirm morphology and transcriptome similarities between cord blood- and iPSCs-derived MKs. A primary selection of 43 candidate TFs was made from comparative analysis of human pluripotent stem cell- and cord blood-derived MK expression arrays and informed by pre- existing knowledge and known protein-
Platelets emeshed in fibrin. Each year a quarter of a million platelet concentrates are used in the UK.
DECEMBER 2013
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