Publications by authors named "Samuel J Machin"

Background: The Sysmex CN-6500 is a new haemostasis analyser with an integrated immunoassay module that performs chemiluminescence enzyme assay (CLEIA) in addition to coagulation, turbidimetric, chromogenic and platelet aggregation tests.

Aims: To evaluate the analytical performance of the CN-6500 against the predicate device (Sysmex HISCL-800) for soluble thrombomodulin (TM), thrombin-antithrombin (TAT), tissue plasminogen activator/plasminogen activator inhibitor 1 complex (tPAI-C) and plasmin α2 plasmin inhibitor complex (PIC) assays.

Methods: Imprecision was assessed by testing two levels of quality control plasmas 10 times on 5 separate days.

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Background: The CN-6000 (Sysmex Corp.) is a new haemostasis analyser with blood coagulation, amidolytic, immuno-turbidometric and light transmission aggregometry (LTA) capabilities. Transmitted light is monitored at multiple wavelengths (340, 405, 575, 660, 800 nm), from an LED light source.

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Finding an inherited complement abnormality in HSCT-associated TMA provides a rationale for the use of a complement inhibitor.Alternative complement inhibitors such as Coversin should be considered in patients who are resistant to eculizumab.

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Background: Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.

Methods: This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily.

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Many modern automated cell counters in high-volume clinical hematology laboratories use new, improved technologies for routine platelet analysis. The latest progress includes the use of state-of-the art information technology, specific fluorescent dyes, and monoclonal antibodies to obtain more reliable platelet counts. This information allows the accurate and precise enumeration of platelets even in thrombocytopenic patients and the reporting of novel platelet parameters.

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Background: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.

Methods: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin.

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Background: Historically, haematology analyser flags for abnormal white blood cells (WBCs) show good sensitivity but lower specificity, causing unnecessary blood film reviews. While the WBC differential channel on Sysmex XE and XN instruments reports a combined flag for blasts/abnormal lymphocytes, the new white precursor cell channel (WPC) on the XN series has been introduced to separate this into a specific flag for either cell type or, if no abnormality, remove the flag entirely.

Aims: To compare the efficiency of abnormal WBC flags from the XN WPC to our existing analyser and determine whether WPC can reduce false positive flags and blood films required.

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Accurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti β2 glycoprotein I (aβ2GPI) antibodies (< 99th centile) and/or certain clinical criteria such as two unexplained miscarriages, three non-consecutive miscarriages, late pre-eclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS.

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The current mainstay of treatment of thrombotic antiphospholipid syndrome (APS) is long term warfarin; however, the optimal antithrombotic treatment for APS-related ischaemic stroke or transient ischaemic attacks (TIA) remains uncertain, as does the optimal intensity of anticoagulation. The risk of bleeding with increasing anticoagulant intensity needs to be balanced against the risk of profound permanent disability and death, or irreversible neurological deterioration as a result of recurrent stroke/TIA. Several experts recommend a target INR of 3.

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Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-γ and IL-17a) were measured in 20 acute TTP patients and 49 remission cases.

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Background: The Sysmex XN haematology instrument performs automatic reflex testing, depending on sample results. A nucleated red blood cell (NRBC) count is provided on all samples. The instrument has a smaller footprint (34%) than previous Sysmex XE analysers.

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Background: Activated protein C resistance (APCR) within a thrombin generation test (TGT) system is associated with an increased risk of venous thromboembolism (VTE). However, application of the TGT is restricted by the analytical platforms used to monitor thrombin generation. Using a routine coagulation analyser we have developed an automated chromogenic TGT that is sensitive to defects in the protein C pathway.

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Introduction: Total hip/knee replacement surgery (THR/TKR respectively) is associated with an increased risk of venous thromboembolism. Dabigatran is recommended as a thromboprophylactic agent post orthopaedic surgery. The aim of this study was to assess the post-operative (Day-1 and Day-2) effect of prophylactic Dabigatran on: the thrombin generation (TG) assay; prothrombin fragment 1.

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A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers.

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Hematology analyzers generate suspect flags in the presence of abnormal cells. False-positive rates for flags are high on all analyzers. Sysmex, Kobe, Japan, has developed new software for its XE-5000 with improved algorithms for flagging blast cells, abnormal lymphocytes or lymphoblasts, and atypical lymphocytes.

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The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated.

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Total hip/knee replacement surgeries are associated with an increased risk of venous thromboembolism and post-operative thromboprophylaxis has become standard treatment. This study aimed to: (i) assess the impact of hip/knee replacement surgery on ex vivo thrombin generation (TG), prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer; (ii) compare the anticoagulant effects of dalteparin and rivaroxaban on TG 24 h after surgery. Haemostatic variables were assessed in plasma samples of 51 patients taken pre-operatively, peri-operatively, and 24 h post-operatively.

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The widespread use of central neuraxial block (CNB) and the prevalence of anticoagulation for different indications have led to an inevitable overlap between the two. The most serious complication of CNB in anticoagulated patients is the risk of spinal/epidural haematoma. Performing CNB in these patients is a complex decision that should take into account the twin risks of bleeding and venous/arterial thrombosis if anticoagulation therapies were to be stopped.

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Thrombotic thrombocytopenic purpura (TTP) in children is rare and is often thought to be due to congenital ADAMTS13 deficiency. We report seven new cases of noncongenital TTP in children and adolescents and perform a review of the literature where ADAMTS13 assays have been performed in paediatric acquired TTP. All new cases were female and the median age was 13 years.

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