HAEMOSTASIS
clinical assessment and the results interpreted accordingly. In an attempt to rationalise the investigation of inherited platelet abnormalities and improve the standardisation of investigative procedures, new guidelines have recently been published by the British Committee for Standards in Haematology.
Inherited platelet abnormalities One of the more recently studied approaches to aid the investigation of platelet abnormalities is genetic analysis. This was reviewed by Dr Andrew Mumford (Bristol) in his presentation Genetic Diagnosis of Heritable Platelet Function Disorders. Congenital platelet function disorders are associated with a wide range of genes and to date only a few specific causative mutations have been identified. In a pilot study of 90 UK subjects with inherited platelet function defects, four patients showed a sufficiently specific phenotype to implicate defects in the thromboxane A2 or P2Y12 ADP receptors. Subsequent genetic diagnosis of these patients was achieved by targeted sequencing of the corresponding TXA2R and P2Y12R genes, and pathogenicity was confirmed by studying the expression of the variant receptors in heterologous cell lines. As phenotypic analysis usually suggests that many, rather than single, candidate genes may be implicated in any one particular abnormality, a collaborative study (UK Genotyping and Platelet Phenotyping Study) has recently been established that involves the simultaneous analysis of 216 selected platelet genes. In a pilot group of 10 patients, this approach yielded high- quality sequence data with good coverage across the target genes in all patients. Using clinical and laboratory data it is hoped that next-generation targeted sequencing may yield multiple candidate single nucleotide variations for each subject. Further research is required to establish what role gene analysis may have in the diagnosis of inherited platelet disorders.
Laboratory error Matters relevant to every laboratory were considered next by Professor Norbert Blankaert (Leuven, Belgium) who discussed Causes of Error in the Laboratory. Risk analysis and risk management are integral components of any quality management system and as such all institutions and laboratories should have appropriate and effective practices in place to minimise the risk of errors occurring. Such systems must consider the whole process, from sample collection to final report. Diagnostic clinical laboratories generally have well- established practices for the quality
30 THE CLINICAL SERVICES JOURNAL
Incases of significant trauma, massive blood loss or major surgery, haemostasis canbe extremely dynamic, with significant changes occurring in the space of a few minutes.
control and quality assurance of analytical processes, but the pre- and post-analytical phases are often comparatively under- considered or neglected. Consequently, studies have shown that it is in these areas that errors are most likely to occur. It has been estimated that between 46% and 68% of errors occur before the sample reaches the laboratory, 19% to 47% of errors occur after the analysis, and only 7% to 14% are related to the analysis itself. The pre-analytical errors fall into one of two main groups: patient and sample misidentification errors, which potentially lead to results being assigned to the wrong patient; and sample quality or suitability errors, which potentially lead to inaccurate results being issued. For haemostasis investigations in particular, the quality of the sample is of paramount importance. Most pre-analytical errors originate at sites remote to the analytical laboratory, such as hospital wards, out- patient clinics, phlebotomy rooms, GP surgeries or centralised specimen reception facilities, and involve a diverse group of staff with varying qualifications, background and training. Considering the significant risk posed by pre-analytical errors, laboratory professionals, by nature of their training and expertise, are probably best qualified to take the lead in developing and implementing procedures and practices to minimise this risk, even when processes occur outside their direct area of responsibility.
Kit evaluation The final presentation of the first day, entitled Kit Evaluation, was given by Dr Chris Gardiner (Oxford). Before any new equipment or kit is purchased it is wise to compare all the potentially suitable alternatives to ensure the best product is obtained with the resources that are available. The popularity of the product, ease of use, method of calibration, internal quality control, external quality assessment data and discussions with sites where the product is currently in use may
all influence the decision. Limited in- house trials with different loaned kits may be possible. Furthermore, before any new kit is used to test patient samples, its suitability for the intended purpose, as claimed by the manufacturer, should be evaluated. The precise evaluation process may vary according to the kit and what it is being used to measure. Comparison with any existing method should always be performed and related to any quoted reference ranges. Checks of precision should be made within-day, day-to-day and between different batches of reagent, using material that is the same as patient sample material. It may also be appropriate to investigate the effect of any potentially interfering substances. All in- house evaluation data should be recorded and saved for future reference. Many evaluation guidelines are available but it should be borne in mind that the majority of these have been produced in a clinical chemistry setting, with well-defined analytes, standardised reference material and a range of suitable matrices. This is often not the case with tests of haemostasis.
Antiphospholipid syndrome The morning session of the second day was chaired by Professor Brian Colvin (UK NEQAS BC steering committee chairman) and the first presentation, Antiphospholipid Syndrome: Unusual Cases, was given by Professor Mike Greaves (Aberdeen). The antiphospholipid syndrome is typically defined by arterial or venous thrombosis, or recurrent miscarriage in a subject in whom laboratory tests for antiphospholipid antibodies are persistently positive. As thrombosis, pregnancy failure and the presence of antiphospholipid antibodies are all relatively common, their co-existence by chance is likely to occur. Many conditions affecting the heart, lungs, eyes, skin, nervous system and blood have been reported to be associated with
MARCH 2012
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