Publications by authors named "Roger Luddington"

The role of the fibrinolytic system in the development of venous thrombosis (VT) is unclear. We studied the risk of first and recurrent VT associated with reduced fibrinolysis, as measured by clot lysis time (CLT). We also studied the relationship between CLT and thrombin generation to determine if any relationship between CLT and VT was affected by thrombin generation.

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In this study, we describe a novel thrombomodulin (TM) mutation (c.1611C>A) that codes for a change from cysteine 537 to a premature stop codon (p.Cys537Stop).

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Background: Coagulopathy is common after cardiopulmonary bypass (CPB), and platelet dysfunction is frequently considered to be a major contributor to excessive bleeding. Exposure to hypothermia may exacerbate the platelet function defect. We assessed platelet function during and after deep hypothermia with multiple electrode aggregometry (Multiplate(®); Verum Diagnostica GmbH, Munich, Germany).

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The thrombin generation test (TGT) has demonstrated utility in evaluating overall hemostatic capacity both in bleeding and thrombotic disorders. Although the test is currently well accepted as a research tool, its role in clinical practice has not yet been defined through large prospective multicenter clinical studies. Such prospective studies have been limited by the lack of official standardization of the assay and its large inter-laboratory variability.

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The thromboelastography trace provides a graphical and numerical representation of the viscoelastic changes associated with fibrin polymerization. When used with whole blood, the shape of this trace is a composite of the effects of white and red cell content and composition, platelet number and function, fibrinogen concentration, as well as coagulation protein function and balance. The trace is also influenced by pharmacological agents such as anticoagulants, antiplatelet therapy, and coagulation factor supplementation.

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Background: Methylene blue (MB) treatment of plasma is known to reduce the activity of clotting factors, but its effect on thrombin generation and clot formation is not well documented.

Study Design And Methods: Individual clotting factors and inhibitors and global tests of thrombin generation and clot formation using rotational thrombelastometry (ROTEM) were assessed in a paired study of standard or MB plasma and cryoprecipitate (n = 20 each).

Results: MB treatment resulted in a 10 percent reduction in endogenous thrombin potential and 30 percent decrease in peak thrombin as well as the expected 20 to 35 percent loss of Factor (F)VIII, fibrinogen, and FXI activity.

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Transmittance waveform (TW) analysis has been proposed as a method of both prediction and monitoring of non-overt and overt disseminated intravascular coagulation. This study assessed the use of the rapidTW of the activated partial thromboplastin time in the detection of sepsis in 49 consecutive neutropenic haemato-oncology patients. A slope 1 cut-off value of -0.

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Haemostatic changes in septic patients are complex, with both procoagulant and anticoagulant changes. Thirty-eight patients with severe sepsis and 32 controls were investigated by coagulation screens, individual factor assays, calibrated automated thrombography (CAT), whole blood low-dose-tissue factor activated (LD-TFA) Rotem and LD-TFA waveform analysis. Thirty-six of 38 patients had an abnormal coagulation screen.

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The thrombin-platelet feedback loop was examined at low concentration tissue factor using calibrated automated thrombography in combination with the elimination of contact factor activation by corn trypsin inhibitor. The results indicated that, when contact factor activation was eliminated, the thrombin-platelet feedback loop was a major determinant of thrombin generating capacity and that platelets had a greater role in regulating the propagation of thrombin generation than its initiation. This method has potential application to the measurement of platelet-dependent thrombin generation in clinical diagnostic laboratories and hence the investigation of patients with apparent hypo- or hypercoagulable phenotypes.

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Background: Stratification for risk of recurrence after a first episode of venous thromboembolism (VTE) would affect the duration of anticoagulant therapy. We aimed to determine the incidence of recurrence of VTE in relation to clinical risk factors and standard laboratory testing for heritable thrombophilic defects.

Methods: We established a database to prospectively follow-up a cohort of unselected patients who had had a first episode of objectively proven VTE.

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