I Jennings

Royal Hallamshire Hospital, Sheffield, ENG, United Kingdom

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Publications (25)102.95 Total impact

  • Article: Investigation of a prolonged APTT. Different approaches taken by laboratories to achieve the same diagnosis.
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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
  • Article: Genetics of haemostasis.
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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. · 2.60 Impact Factor
  • Article: Novel analysis of clinically relevant diagnostic errors in point-of-care devices: a rebuttal.
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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. · 5.73 Impact Factor
  • Article: Management of patients receiving oral anticoagulants using computer dosing software--does everyone agree? Data from a UK NEQAS (blood coagulation) exercise.
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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
  • Article: Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time: a rebuttal.
    Journal of Thrombosis and Haemostasis 09/2009; 7(12):2157-8; author reply 2178-9. · 5.73 Impact Factor
  • Article: Laboratory performance in the World Federation of Hemophilia EQA programme, 2003-2008.
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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. · 2.60 Impact Factor
  • Article: Platelet function testing: practice among UK National External Quality Assessment Scheme for Blood Coagulation participants, 2006.
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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
  • Article: Quality assurance for oral anticoagulation self management: a cluster randomized trial.
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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. · 5.73 Impact Factor
  • Article: External quality assessment for prothrombin time/international normalised ratio using point-of-care devices: split-sample or conventional external quality assessment using control samples?
    Scandinavian Journal of Clinical and Laboratory Investigation 02/2007; 67(7):673-5; author reply 676-7. · 1.38 Impact Factor
  • Article: Point of care testing by health care professionals: current practice amongst the UK National External Quality Assessment Scheme Participants.
    British Journal of Haematology 08/2005; 130(2):320-1. · 4.94 Impact Factor
  • Article: Lupus anticoagulant testing using plasma spiked with monoclonal antibodies: performance in the UK NEQAS proficiency testing programme.
    I Jennings, I Mackie, J Arnout, F E Preston
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    ABSTRACT: We report here results from a United Kingdom National Quality Assessment Scheme (UK NEQAS) exercise in which both plasma spiked with monoclonal antibodies and plasma from a patient known to have lupus anticoagulant (LA) were distributed to 245 hemostasis laboratories with a request for them to test for possible LA using their routine screening procedure. In general, good agreement was seen in the diagnosis of samples spiked with monoclonal antibodies against beta2-glycoprotein 1 (beta2GP1) and prothrombin, the LA-positive patient sample, and a normal pooled plasma; over 87% of centers correctly identified each sample. However, methods employing platelet neutralizing procedures were associated with a higher proportion of false-negative responses with the antiprothrombin-spiked sample, and it is important to recognize that sensitivity and responsiveness of different methods may vary between artificial plasmas and different LA-positive patient plasmas.
    Journal of Thrombosis and Haemostasis 01/2005; 2(12):2178-84. · 5.73 Impact Factor
  • Article: SSC/ISTH classification of hemophilia A: can hemophilia center laboratories achieve the new criteria?
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    ABSTRACT: To assess the practicality of the recent Scientific and Standardization committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) recommendations in respect of the classification of hemophilia we distributed samples from three untreated subjects with hemophilia A to 91 UK hemophilia centers (HCs), comprising 20 comprehensive care centers (CCCs) and 71 HCs. Laboratories were requested to perform their routine factor (F)VIII:C assays and to classify the severity of hemophilia. Median values of < 1 U dL-1 were obtained on two samples. However, for each of the two, approximately 30% of laboratories obtained results in the range 1-29 U dL-1 and 1-33 U dL-1 respectively. For one of these samples 17 laboratories diagnosed severe hemophilia despite obtaining FVIII:C levels in the range 1-5 U dL-1. The median FVIII:C for the third sample was 5.8 U dL-1 with a range of 1.5-36 U dL-1. For this sample eight centers diagnosed severe hemophilia. Fifty-four laboratories obtained a result > 5 U dL-1; 21 of these diagnosed mild hemophilia, 31 moderate hemophilia and two severe hemophilia. Results from CCCs were more accurate and more precise than those from HCs. Our results indicate a need for improved standardization of FVIII assays. In the UK there remains a lack of consensus in respect of the laboratory diagnostic criteria for the classification of hemophilia A.
    Journal of Thrombosis and Haemostasis 03/2004; 2(2):271-4. · 5.73 Impact Factor
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    Article: Problems relating to the laboratory diagnosis of factor XIII deficiency: a UK NEQAS study.
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    ABSTRACT: Familial (F)XIII deficiency is an extremely rare bleeding disorder. In most laboratories the diagnosis is initially established through a clot-solubility screening test. We report here results from a series of UK NEQAS (Blood Coagulation). Proficiency Testing investigations, in which laboratories were provided with samples from normal individuals and from various subjects with FXIII deficiency with a request to perform their usual test for this disorder and to provide an interpretation of their results. Over 95% of centers were able to diagnose severe familial FXIII deficiency in previously untreated patients and to identify samples from normal subjects. However, both quantitative and qualitative methods produced widely variable results on samples obtained from previously treated individuals with FXIII deficiency but having measurable levels of FXIII. Data generated by UK NEQAS investigations suggested that solubility tests employing thrombin show greater sensitivity to FXIII deficiency, and this was confirmed in a subsequent single-center study. Our results lead us to recommend the use of thrombin and acetic acid in the clot-solubility screening test. Use of sensitive screening tests, and improvement in the accuracy and precision of quantitative FXIII assays will aid study of the clinical importance of moderate FXIII deficiency.
    Journal of Thrombosis and Haemostasis 01/2004; 1(12):2603-8. · 5.73 Impact Factor
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    Article: Patient self-management of oral anticoagulation and external quality assessment procedures.
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    ABSTRACT: The role of external quality assessment (EQA) is a contentious issue for patient self-management (PSM) of oral anticoagulation. Patients from general practices in the West Midlands undertaking PSM were recruited to compare efficacy of patients' and health professionals' EQA procedure using the UK National External Quality Assessment Scheme (NEQAS). Patients using Coaguchek (Roche Diagnostics) were trained to perform EQA as part of their PSM training. They undertook PSM for 26 weeks and were asked to perform EQA using material provided by the UK NEQAS twice at home without supervision and twice at the practice with supervision. Patients' results were compared with health care professional users of Coaguchek S. Twenty-three PSM patients were compared with 75 health care professional users of the NEQAS scheme. The PSM group international normalized ratio (INR) percentage time in range was 74%. There was no significant difference in the median results on NEQAS samples obtained by the patients and those obtained by professionals. Three patients were outwith consensus (results > 15% from the median INR) on more than one occasion. Patients were able to perform the EQA tests competently. The data show that good agreement can be achieved between patients analysing the same EQA samples, with coefficients of variation ranging from 22.3% to as low as 5.4%. Further study is required to determine how precision within these EQA schemes relates to the stability of treatment in patients' management of their own anticoagulation.
    British Journal of Haematology 09/2003; 122(5):825-8. · 4.94 Impact Factor
  • Article: Sensitivity of functional protein S assays to protein S deficiency: a comparative study of three commercial kits.
    Journal of Thrombosis and Haemostasis 06/2003; 1(5):1112-4. · 5.73 Impact Factor
  • Article: Between-centre agreement in homocysteine assays: experience from the UK NEQAS proficiency testing scheme.
    Thrombosis and Haemostasis 06/2002; 87(5):921-2. · 5.04 Impact Factor
  • Article: Further evidence that activated protein C resistance affects protein C coagulant activity assays.
    Thrombosis and Haemostasis 02/2000; 83(1):171-2. · 5.04 Impact Factor
  • Article: A UK National External Quality Assessment scheme (UK Neqas) for molecular genetic testing for the diagnosis of familial thrombophilia.
    Thrombosis and Haemostasis 12/1999; 82(5):1556-7. · 5.04 Impact Factor
  • Article: Normalization does not improve between-laboratory agreement but may improve specificity of some assays for activated protein C resistance.
    Blood Coagulation and Fibrinolysis 11/1999; 10(7):451-3. · 1.24 Impact Factor
  • Article: Lipid composition of seven APTT reagents in relation to heparin sensitivity.
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    ABSTRACT: The phospholipid content of different activated partial thromboplastin time (APTT) reagents was determined and compared to heparin sensitivity. The seven reagents included were those most widely used amongst participants of the U.K. National External Quality Assessment Scheme (NEQAS) at the time of study. Heparin sensitivity was assessed using the APTT ratios obtained by more than 300 NEQAS participants on five plasmas prepared from patients receiving unfractionated heparin. The concentrations of three neutral lipids and six phospholipids present in the seven APTT reagents were determined by high-performance thin-layer chromatography (HPTLC) and densitometry. Both the concentrations and the relative percentages of individual phospholipid components varied markedly between reagents. The total phospholipid concentration included a 12-fold range from 16 to 205 microgram/ml. Phosphatidylserine (PS) was completely lacking from one reagent prepared from vegetable material and ranged from 3 to 22 microgram/ml in the other six reagents containing extracts from animal tissue. The concentration of phosphatidylcholine ranged from 3 to 109 microgram/ml. There was no demonstrable relationship between the concentration of any individual lipid components and heparin sensitivity. However, the relative percentage phospholipid composition was important since a lower % of PS or phosphatidylinositol (PI) correlated with increasing heparin sensitivity.
    British Journal of Haematology 10/1999; 106(3):801-8. · 4.94 Impact Factor