I Jennings

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England, United Kingdom

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Publications (47)201.29 Total impact

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    British Journal of Haematology 08/2014; · 4.94 Impact Factor
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    ABSTRACT: Molecular genetic analysis of families with hemophilia and other heritable bleeding disorders is a frequently requested laboratory investigation. In the United Kingdom, laboratories undertaking genetic testing must participate in a recognized external quality assessment scheme for formal accreditation. The UK National External Quality Assessment Scheme (UK NEQAS) for heritable bleeding disorders was established in its current format in 2003, and currently has 27 registered participants in the United Kingdom, the European Union (EU), and the non-EU countries. Two exercises per annum are circulated to participants comprising either whole blood or DNA isolated from cell lines, and laboratories are allowed 6 weeks to analyze the samples and generate a report. Reports are assessed by a panel comprising clinicians and scientists with expertise in this area. Samples to date have involved analysis of the F8 gene (10 exercises), the F9 gene (4 exercises), and the VWF gene (3 exercises) and have comprised a wide spectrum of mutations representing the routine workload encountered in the molecular genetics laboratory. The majority of laboratories in each exercise passed, but a small number did not and reasons for failing included clerical errors, genotyping inaccuracies, and a failure to correctly interpret data. Overall we have seen an improvement in quality of reports submitted for assessment, with a more concise format that will be of value to referring clinicians and counsellors. Informal feedback from participants has been very positive.
    Seminars in Thrombosis and Hemostasis 02/2014; · 4.22 Impact Factor
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    ABSTRACT: A diagnosis of hemophilia A or hemophilia B begins with clinical assessment of the patient and is facilitated by laboratory testing. The influence of the latter on a diagnosis of hemophilia A or hemophilia B is clear-a diagnosis cannot be made without laboratory confirmation of a deficiency of factor FVIII (FVIII) or factor IX (FIX), respectively. Moreover, the degree of hemophilia severity is specifically characterized by laboratory test results. In turn, patient management, including choice and application of therapies, is influenced by the diagnosis, as well as by identification of respective disease severity. An incorrect diagnosis may lead to inappropriate management and unnecessary therapy, and thus to adverse outcomes. Moreover, identification of factor inhibitors in hemophilia will lead to additional and differential treatments, and incorrect identification of inhibitors or inhibitor levels may also lead to inappropriate management. Problems in hemophilia diagnosis or inhibitor detection can occur at any stage in the clinical diagnosis/laboratory interface, from the "pre-preanalytical" to "preanalytical" to "analytical" to "postanalytical" to "post-postanalytical." This report outlines the various problems in laboratory testing for hemophilia and provides various strategies or solutions to overcome these challenges. Although some outlined solutions are specific to the potential errors related to hemophilia, others are general in nature and can be applied to other areas of laboratory hemostasis. Key to improvement in this area is adoption of best practice by all involved, including clinicians, phlebotomists, and laboratories. Also key is the recognition that such errors may occur, and thus that clinicians should assess laboratory test results in the context of their patient's clinical history and follow-up any potential errors, thus avoid misdiagnoses, by requesting repeat testing on a fresh sample.
    Seminars in Thrombosis and Hemostasis 09/2013; · 4.22 Impact Factor
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    ABSTRACT: INTRODUCTION: The APTT is widely employed as part of a coagulation screening panel, used as a pre-operative assessment of bleeding risk, to detect hereditary and acquired haemostatic defects and to monitor anticoagulant therapy. External quality assessment (EQA) exercises assess laboratory performance of individual tests, but rarely assess the approach to investigation of an abnormal result. METHODS: A multicentre exercise was carried out to investigate the ability of laboratories to identify the cause of a prolonged APTT. A sample was distributed with a request to carry out whichever tests were considered necessary to achieve a probable diagnosis. RESULTS: One hundred and ten centres in the UK NEQAS programme took part, and all 104 centres providing an interpretation correctly identified deficiency of FVIII in the sample. However, of these, 10 centres reported additional defects, including lupus anticoagulant, FIX deficiency, FXII deficiency and a FVIII inhibitor. CONCLUSIONS: A markedly varied approach to investigation of a prolonged APTT was observed, although a lack of clinical information may have contributed to this finding.
    International journal of laboratory hematology 11/2012; · 1.30 Impact Factor
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    ABSTRACT: BACKGROUND: Vitamin K antagonists have been used for many decades and have been traditionally monitored by the measurement of the International Normalised Ratio (INR) in the laboratory. Introduction of Point of Care (POC) testing devices to measure INR has resulted in many tests being undertaken in primary care. External Quality Assessment (EQA) of these POC devices is recommended to ensure accuracy and reliability of INR results outside a laboratory setting. AIM: To assess the quality of INR results for users of two POC devices (CoaguChek XS and CoaguChek XS Plus) over a four-year period. METHODS: Four surveys (two samples) were sent in each 12-month period. The median INR value of each sample was calculated and the percentage deviation from this median determined. Any results greater than 15% from the median were considered to be outside consensus which indicated a possible problem within the testing system. RESULTS: Variability of INR results in this UK National External Quality Assessment Scheme (NEQAS) programme was comparable to that in the UK NEQAS EQA programme for laboratory INR testing. Occurrence of persistent problems was lower in the POC programme than the laboratory programme. CONCLUSIONS: Utilisation of an EQA programme for POC devices in primary care is feasible and necessary. Our data suggest for those health professionals using EQA, the reliability and accuracy of INR testing matches the quality of laboratory testing.
    Journal of clinical pathology 10/2012; · 2.43 Impact Factor
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    ABSTRACT: Congenital defects of platelets or plasma proteins involved in blood coagulation generally lead to bleeding disorders. In some of these disorders, patients with a severe phenotype are prone to spontaneous bleeds with critical consequences. This situation occurs more commonly in haemophilia A and haemophilia B and to a certain extent in severe forms (type 3) of von Willebrand disease. Defects in other plasma coagulation proteins and platelet factors are relatively rare, with an incidence of ≤ 1: 1-2 million. Molecular genetic studies of the human coagulation factors, especially factors VIII and IX, have contributed to a better understanding of the biology of these genetic disorders, the accurate detection of carriers and genetic counselling, and have also fostered new therapeutic strategies. This article reviews the evolution of genetics over the last five decades as a tool for bleeding disorder investigations, the recent advances in molecular techniques that have contributed to improved genetic diagnosis of this condition, and the development and utility of proficiency testing programmes and reference materials for genetic diagnosis of bleeding disorders.
    Haemophilia 07/2012; 18 Suppl 4:73-80. · 3.17 Impact Factor
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    ABSTRACT: von Willebrand disease (VWD) is the most common inherited bleeding disorder, but variable severity and several classification types mean that diagnosis is often not straightforward. In many countries, the assays are not readily available and/or are not well standardized. The latest methods and the basis of VWD are discussed here, together with information from the international quality assessment programme (IEQAS). Factor XIII deficiency is a rare, but important bleeding disorder, which may be missed or diagnosed late. A discussion and update on this diagnosis is considered in the final section of our review.
    Haemophilia 07/2012; 18 Suppl 4:66-72. · 3.17 Impact Factor
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    ABSTRACT: See also Shermock KM, Kraus P, Streiff MB. Novel analysis of clinically relevant diagnostic errors in point-of-care devices: a reply to a rebuttal. This issue, pp 1192-4; Shermock KM, Streiff MB, Pinto BL, Kraus P, Pronovost PJ. Novel analysis of clinically relevant diagnostic errors in point-of-care devices. J Thromb Haemost 2011; 9: 1769-75.
    Journal of Thrombosis and Haemostasis 06/2012; 10(6):1191-2; author reply 1192-4. · 6.08 Impact Factor
  • J Clin Pathol. 01/2012;
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    Journal of Thrombosis and Haemostasis 07/2011; 9(10):2117-9. · 6.08 Impact Factor
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    ABSTRACT: The quality of anticoagulation management is not readily or frequently assessed, particularly between different centres. This study sought to evaluate agreement in oral anticoagulant management decisions between participating centres in UK NEQAS programmes. Participants were asked to indicate whether they used computerized dosing support software (CDSS) and to complete a series of questions with respect to anticoagulant management provision. Four clinical scenarios were provided, together with past and current International Normalised Ratio (INR) results. Participants were asked to provide recommendations on the target INR they would assign to the patient, the dose of warfarin and a recall interval. Seven hundred and fifty-nine centres returned results, of which 28% were enrolled in the hospital-based EQA programme, and 72% were participants in the point-of-care testing programme. Six hundred (79%) reported use of CDSS. In one straightforward scenario, there was 99% agreement in dose recommendation. However, for three more complex scenarios, differences were apparent in target INRs employed and both dose and recall recommendations. In some cases, differences related to the software system employed. The study emphasizes large variation in the approach to managing these scenarios and warrants further investigation, together with education including promoting national guidelines for the assignment of target ranges.
    International journal of laboratory hematology 07/2011; 34(1):70-80. · 1.30 Impact Factor
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    ABSTRACT: Global hemostasis devices are currently being employed in operating rooms to assess the bleeding risk and outcomes for patients undergoing surgery. Two devices currently available are the TEG (Thromboelastograph; Haemoscope Corp., Niles, IL) and the ROTEM (Rotation Thromboelastometer; Pentapharm GmbH, Munich, Germany). Both measure the speed of clot formation, the strength of the clot when formed, and clot fibrinolysis kinetics. The two devices use different parameters so no cross comparisons of results can be made. The devices are usually operated by a member of the operating team and not a laboratory scientist; thus their testing and performance is generally not laboratory controlled, despite quality control being required to ensure reliable results. The UK National External Quality Assessment Scheme (NEQAS) for Blood Coagulation has undertaken a series of exercises evaluating the provision of External Quality Assessment (EQA) material for these devices. A series of four studies have taken place using lyophilized plasmas as the test material. Up to 18 TEG users and 10 ROTEM users have been involved in testing two samples per study, for a total of eight samples tested. The samples were normal plasmas, factor VIII or XI deficient samples, or normal plasmas spiked with heparin. The precision of the tests varied greatly for both devices, with coefficients of variances ranging from 7.1 to 39.9% for TEG and 7.0 to 83.6% for ROTEM. Some centers returned results that were sufficiently different from those obtained by other participants to predict alterations in patient management decisions. Our data indicate that regular EQA/proficiency testing is needed for these devices.
    Seminars in Thrombosis and Hemostasis 10/2010; 36(7):757-63. · 4.22 Impact Factor
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    ABSTRACT: We report the results of external quality assessment exercises in which 60 to 120 centers performed factor VIII (FVIII) inhibitor testing on a series of samples over a 13-year period. Samples from seven different subjects were distributed for analysis comprising the following: four different subjects with severe hemophilia A with antibodies following replacement therapy, one subject with acquired hemophilia A and antibodies to FVIII, one subject with normal FVIII and an easily detected lupus anticoagulant, and one subject with mild hemophilia A and a difficult-to-detect lupus anticoagulant but without antibodies to FVIII. In all of the surveys the results obtained in different centers analyzing the same sample varied to an extent that would influence patient management decisions. In the UK National External Quality Assessment Scheme surveys reported here, there was considerable interlaboratory variation in the results of FVIII inhibitor testing that did not improve over the survey period. The coefficient of variation of results in different centers was between 33% and 106% in samples from patients with severe congenital hemophilia A. In some cases, results were affected by assay components. For one plasma, the mean FVIII inhibitor results in centers using one source of normal plasma was 3.9 Bethesda unit (BU)/mL compared with a mean of 5.7 BU/mL in centers using a different normal plasma source ( P = 0.04). Our data indicate that the detection of FVIII inhibitors is not the same in different centers, and the degree of variability noted makes it likely that assay variability has contributed to the lack of international consensus in relation to the real incidence of FVIII inhibitors in different clinical settings. Improvements in assay standardization are urgently needed.
    Seminars in Thrombosis and Hemostasis 11/2009; 35(8):778-85. · 4.22 Impact Factor
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    Journal of Thrombosis and Haemostasis 09/2009; 7(12):2157-8; author reply 2178-9. · 6.08 Impact Factor
  • Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 08/2009; 20(5):388-90. · 1.25 Impact Factor
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    ABSTRACT: External quality assessment (EQA) has been shown to improve laboratory performance and diagnosis in haemostasis. We report here findings from the World Federation of Haemophilia (WFH) EQA programme during the period 2004-2007. Samples for PT, APTT, FVIII:C, FIX:C and VWF assays were distributed to centres in both established and emerging countries, and results were compared with results obtained by United Kingdom National External Quality Assessment Scheme (UK NEQAS) participants on the same samples. In general, good agreement was seen throughout between WFH and UK NEQAS for screening tests, and it was possible to identify an improvement in WFH centre agreement for results for VWF assays during the period of study. Agreement between emerging and established WFH centres was comparable for screening tests, possibly indicative of the relative simplicity of these tests and the degree of automation now employed in almost all haemostasis laboratories. However, CVs and performance compared with UK NEQAS participant results for factor assays amongst established centres was better than between emerging centres. Distribution of a questionnaire revealed different application of methodology for these assays, which may contribute to the observed difference in performance. Several centres participated in supplementary exercises, with comparable results obtained by emerging and established centres performing FVIII and fibrinogen measurement on cryoprecipitate, and all centres performing FVIII inhibitor assays correctly identifying the presence of an inhibitor. Participation in EQA programmes should continue to encourage improvement in laboratory performance and therefore improvements in the diagnosis and care of patients with haemophilia.
    Haemophilia 02/2009; 15(2):571-7. · 3.17 Impact Factor
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    ABSTRACT: Point-of-care (POC) testing in the field of hemostasis is rapidly expanding in many countries. This includes use of global tests of hemostasis in operating theaters and especially use of POC monitors for determination of the international normalized ratio (INR) for monitoring oral anticoagulant therapy. Issues related to internal quality control and external quality assessment for these devices are reviewed. Data from external quality assessment exercises involving users of several different POC-INR devices is described, and use of split samples where a patient sample is analyzed by both a POC device and by a conventional laboratory method is described.
    Seminars in Thrombosis and Hemostasis 11/2008; 34(7):647-53. · 4.22 Impact Factor
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    ABSTRACT: Platelet function testing forms an important part of the laboratory investigation of a bleeding tendency; however, little standardisation and quality control is available for these tests. A UK National External Quality Assessment Scheme (UK NEQAS) for Blood Coagulation exercise sought to identify current practice among laboratories performing platelet function tests. A questionnaire was circulated in March 2006 to establish the current status of platelet function testing practice among participants of UK NEQAS. Participants were asked specifically about practice in bleeding time testing, PFA-100 analyser use, platelet aggregometry methodology and additional tests of platelet function. 169 returned questionnaires revealed that 26 centres used bleeding time, the PFA-100 analyser and platelet aggregometry in their investigations; 13 used bleeding time and the PFA-100 only; 33 used bleeding time and platelet aggregometry; and 23 used the PFA-100 with platelet aggregometry. 58 centres reported that they performed only bleeding times in their investigations, 10 reported use of the PFA-100 only, and 6 reported use of aggregometry only. Marked variability was observed in methodology for each of these tests, and in many cases no form of quality control was employed. The data confirmed the lack of standardisation in methodology employed in different centres. Updated guidelines and standardisation of platelet function assessment are required to facilitate comparability between centres.
    Journal of clinical pathology 09/2008; 61(8):950-4. · 2.43 Impact Factor
  • American Journal of Clinical Pathology 06/2008; 129(5):825-6. · 2.88 Impact Factor
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    ABSTRACT: External quality assessment (EQA) should be an inherent component of patient self management (PSM) of oral anticoagulation. The aim of this study was to evaluate methods of EQA for patients within a cluster randomized trial. After development of methods, general practises were randomly allocated to a formal EQA scheme of patients performing the test independently at home or at their practise with supervision. The supervised group of practises was further sub divided to test two other EQA methods: (i) venous sample compared with patients' point of care (POC) device; and (ii) patients POC compared with reference POC. Primary trial outcome measure was reliability of results from the formal scheme taking into account adherence and test errors. Proportion of EQA scheme tests in range was 633/836 (75.7%). Proportion in range was significantly higher in group performing independently compared with supervised group, 80.1% vs. 71.5% respectively, P = 0.02. Sixty-six percent of tests were in range with venous compared with patients POC, and 88% in patients POC compared with reference POC. Patients are able to undertake a formal EQA scheme and perform more reliably at home independently. There are satisfactory alternatives if a formal scheme is not acceptable.
    Journal of Thrombosis and Haemostasis 04/2008; 6(3):464-9. · 6.08 Impact Factor