S Dunkley

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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Publications (24)64.63 Total impact

  • P. Williams · K. Yang · G. Kershaw · G. Wong · S. Dunkley · P.C.A. Kam
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    ABSTRACT: This study evaluated the effects of haemodilution with either 6% hydroxyethyl starch (HES) 130/0.4 (Voluven®) or 0.9% normal saline (NS) on blood coagulation in vitro. Haemodilution with 6% HES 130/0.4 impaired coagulation, as indicated by the changes in thromboelastographic parameters k-time, a-angle and maximum amplitude. Light transmission aggregometry and multiple electrode aggregometry demonstrated that impaired platelet receptor function occurred only at high levels of haemodilution (40%) with both fluids, but there was no significant difference between the two fluids (P=0.05). The thromboelastographic functional fibrinogen assay showed that the fibrinogen component of clot strength was significantly impaired with haemodilution with HES 130/0.4 compared with haemodilution with NS (whole blood [14.4±4.6 mm] versus 40% HES dilution [3.7±1.9], [P=0.001]; versus 40% NS dilution [10.4±4.6], [P=0.129]). These findings suggest that there is little difference between HES or NS in relation to coagulation or platelet function during minor or moderate haemodilution, but at high levels of haemodilution with HES, fibrinogen activity is more impaired compared with NS.
    No preview · Article · Nov 2015
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    ABSTRACT: Joint health and life expectancy for people with haemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services. This paper aims to highlight such challenges and propose practical solutions. Nine haemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in haemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these. Demography, optimising treatment and assessing treatment success were identified as broad areas of challenge which included: co-morbidities in ageing patients; transitioning from paediatric to adult care; equity of care for remote populations; weight-based dosing in obese patients; tailoring prophylaxis; accurate diagnosis of acute joint pain; managing chronic arthropathy; providing psychosocial support; consistency in definitions and assessment; and quantifiable outcome measures. Practice points included increased cross-speciality coordination and including psychologists and rheumatologists as part of comprehensive care teams; close collaboration between paediatric and adult centres to facilitate transition of care; systems such as telehealth that ensure continuity of care for remote populations; using pharmacokinetic data to tailor therapy; rapid and accurate diagnosis of acute joint pain; using data from bleeding registries to assess treatment effects and help with service planning; and ensuring consistency through benchmarking and standardisation of HTCS. Achieving treatment equity, optimal outcomes and cost savings may be possible through investing in national governance structures, expanding the comprehensive model of care and implementing innovative solutions tailored to local needs.
    No preview · Article · Aug 2015 · Current Medical Research and Opinion
  • S Pathirana · G Wong · P Williams · K Yang · G Kershaw · S Dunkley · P C A Kam
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    ABSTRACT: We investigated the in vitro viscoelastic changes of progressive haemodilution with 4% albumin compared with normal saline (NS) using rotational thromboelastometry (ROTEM(®), Pentapharm Co., Munich, Germany). Whole blood samples obtained from 20 healthy volunteers were diluted in vitro with 4% albumin or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM(®) (EXTEM [screening test for the extrinsic haemostasis system], FIBTEM [EXTEM-based assay for the fibrin part of the clot]) variables including coagulation time, clot formation time (CFT), α-angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each degree of haemodilution. There was no significant difference in fibrinogen concentration at equivalent haemodilutions with normal saline and 4% albumin solutions. Forty percent haemodilution with albumin significantly prolonged coagulation time (EXTEM P=0.007, FIBTEM P=0.0001) and significantly decreased lysis index (FIBTEM P=0.009) compared with NS. A significant decrease in maximum clot firmness from undiluted measurements (P=0.05) was observed at lower haemodilutions with albumin (20% with EXTEM, 10% with FIBTEM) compared with NS (40% with EXTEM and FIBTEM). The adverse effects of large degrees of haemodilution with 4% albumin solution are in excess of what can be explained by haemodilution alone. This study suggests that large degrees of haemodilution with albumin impair fibrinogen activity to a greater extent than equivalent degrees of haemodilution with NS.
    No preview · Article · Mar 2015 · Anaesthesia and intensive care
  • C Barnes · S A Brown · J Curtin · S Dunkley
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    ABSTRACT: Immune tolerance induction (ITI) is the preferred management of haemophilia A patients who develop high titre inhibitors against factor VIII. However, the optimal ITI regimen, predictors of ITI outcome and definitions of successful and unsuccessful ITI remain unclear. The aim of this project was to develop a consensus on the definition of ITI treatment failure for Australian clinical practice using a modified Delphi approach. Three consecutive surveys were distributed to the directors of 17 haemophilia treatment centres in Australia. Participants were asked to rate their agreement with definitions of ITI treatment failure generated from a literature review. Thirty-five statements regarding ITI achieved consensus (majority agree or strongly agree) during the three survey rounds. After round 3, four statements achieved majority disagreement, and for two statements no consensus was reached. Our study demonstrates that clinicians in Australia necessitate an arbitrary time to assess ITI failure, but that clinical outcomes of ITI are important in assessing response. Assessment over any 3- to 6-month period without a 20% reduction in inhibitor titre is suggestive of failure, but a reduction in bleeding phenotype alone may be sufficient to continue ITI. Overall, a period of 3 or 5 years of ITI may be required to determine response to ITI. Documentation of improvement in clinical measures, supported by the laboratory features of factor VIII inhibitor levels and pharmacokinetics, is essential in assessing the success of failure of ITI in these patients.
    No preview · Article · Jul 2014 · Haemophilia
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    ABSTRACT: Background and Objectives The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies.Materials and Methods Data were extracted on all patients who received red blood cell (RBC) transfusions in 2010 at three tertiary Australian hospitals. MT patients were identified according to three definitions: ≥10 units RBC in 24 h (10/24 h), ≥6 units RBC in 6 h (6/6 h) and ≥5 units RBC in 4 h (5/4 h). Clinical coding data were used to assign bleeding context. Data on in-hospital mortality were also extracted.ResultsFive hundred and forty-two patients met at least one MT definition, with 236 (44%) included by all definitions. The most inclusive definition was 5/4 h (508 patients, 94%) followed by 6/6 h (455 patients, 84%) and 10/24 h (251 patients, 46%). Importantly, 40–55% of most types of critical bleeding events and 82% of all obstetric haemorrhage cases were excluded by the 10/24 h definition. Patients who met both the 5/4 h and 10/24 h definitions were transfused more RBCs (19 vs. 8 median total RBC units; P < 0·001), had longer ventilation time (120 vs. 55 h; P < 0·001), median ICU (149 vs. 99 h; P < 0·001) and hospital length of stay (23 vs. 18 h; P = 0·006) and had a higher in-hospital mortality rate (23·3% vs. 16·4%; P = 0·050).Conclusion The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort.
    No preview · Article · Apr 2014 · Vox Sanguinis
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    ABSTRACT: The management of bleeds in patients with haemophilia A or B complicated by inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is an established therapy in these patients. To develop a consensus-based guide on the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine expert haemophilia specialists from Australia and New Zealand developed practice points on the usage of rFVIIa, based on their experience and supported by published data. Practice points were developed for 13 key topics: control of acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough bleeding during surgery or treatment of acute bleeds; paediatric use; use in elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds; clinical monitoring of therapy; laboratory monitoring of therapy; concomitant antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa is important in allowing patients to administer treatment early in bleed management. In adults, 90-120 μg/kg is the favoured starting dose in most settings. Initial dosing using 90-180 μg/kg is recommended for children due to the effect of age on the pharmacokinetics of rFVIIa. In the management of acute bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with concomitant antifibrinolytic medication unless contraindicated. The practice points provide guidance on the usage of rFVIIa for all clinicians involved in the management of haemophilia complicated by inhibitors.
    Full-text · Article · Nov 2012 · Internal Medicine Journal
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    ABSTRACT: Studies have shown dabigatran to be an effective anticoagulant with an acceptable bleeding profile. None the less, these patients do suffer from bleeding complications. Unfortunately, there are currently no direct reversal agents to dabigatran or established guidelines on the management of bleeding in these circumstances. We examined the effects on thrombin generation parameters, after ex-vivo spiking the plasma of patients on dabigatran (n = 8) with FEIBA®. These parameters were measured using the calibrated automated thrombography (CAT) machine. In our study, we showed the ability of FEIBA® to improve the abnormal thrombin generation parameters caused by dabigatran in these patients. This provides evidence, lacking in the literature, that this agent may be able to provide haemostatic support in situations where dabigatran induced coagulopathy exists.
    Full-text · Article · Sep 2012 · International journal of laboratory hematology
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    ABSTRACT: von Willebrand's disease (VWD) is an inherited bleeding disorder characterized by deficient levels of or dysfunctional von Willebrand factor (VWF). This phase II/III open-label, multicentre study evaluated the efficacy and safety of BIOSTATE, a high purity plasma-derived double-virus inactivated FVIII/VWF concentrate, when used in non-surgical bleeds, surgical procedures and prophylactic therapy in VWD patients for whom desmopressin treatment was deemed ineffective, inadequate or contraindicated. Twenty three patients (7 type 1, 9 type 2 and 7 type 3; 12 male, 11 female), who received FVIII/VWF concentrate as part of their VWD management, were recruited prospectively between December 2004 and May 2007 from eight centres in Australia and New Zealand. BIOSTATE dosing was based on pre-treatment FVIII:C and/or VWF:RCo plasma levels and a predetermined dosing guide. Haemostatic efficacy of BIOSTATE was rated as excellent or good for all major and minor surgery events, long-term prophylaxis, and for four of the six assessable non-surgical bleeding events. Blood transfusions were required by two major surgery patients as well as one patient with a non-surgical bleed. The median overall exposure to BIOSTATE across all groups was 8 days, greater in the prophylactic group (range 53-197) compared with major surgery (3-24), minor surgery (1-8) and non-surgical bleeds (1-10). BIOSTATE was shown to be efficacious and well tolerated when treating patients with VWD. This study also provides important insights into dosing regimens with BIOSTATE and the role of monitoring therapy with FVIII:C and VWF:RCo.
    No preview · Article · Mar 2010 · Haemophilia
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    L. Phillips · V. Nguyen · S. Dunkley · J. Isbister · P. Cameron

    Full-text · Article · Feb 2009 · Injury
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    ABSTRACT: There has been increasing off-label use of recombinant activated factor VII (rFVIIa/NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) for patients with critical bleeding. Given the lack of high-level evidence, the clinical indications, observed response and adverse events are important to capture. The Haemostasis Registry collects retrospective and contemporaneous data on all use of rFVIIa at participating institutions for non-haemophiliac patients with critical bleeding (i.e. off-label use). As of October 2006, 694 cases had been reported into the register from 37 hospitals across Australia and New Zealand. These comprise an array of therapeutic categories, including salvage use in: perioperative cardiothoracic surgery (44%), trauma (16%), medical bleeding (9%), obstetric bleeding (4%) and other types of critical bleeding (28%). Patients received a median (interquartile range) dose of 91 mug/kg (75-103) and 83% of patients received a single dose of rFVIIa. The documented response rate to a single dose of rFVIIa was 69%. The 28-day survival was 68%, but varied with clinical category. The rate of adverse events probably or possibly linked to the use of rFVIIa was 6%, with most of the thromboembolic adverse events occurring in the cardiac surgery group. The Haemostasis Registry cannot replace well-designed prospective randomized controlled trials, but in their absence this registry provides a basis for understanding current clinical experience of rFVIIa. Registries continue to be vital in monitoring off-label uses of medications.
    No preview · Article · Apr 2008 · Internal Medicine Journal

  • No preview · Article · Dec 2007 · Heart, Lung and Circulation
  • J. Isbister · S. Dunkley · P. Cameron · L. Phillips

    No preview · Article · Nov 2007 · ISBT Science Series
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    S Dunkley · L Gaudry

    Preview · Article · Jul 2007 · Journal of Thrombosis and Haemostasis
  • J Shortt · S Dunkley · K Rickard · R Baker · A Street
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    ABSTRACT: Biostate is a double virally inactivated, plasma derived coagulation factor VIII (FVIII)/von Willebrand factor (VWF) concentrate registered and used in Australia, New Zealand and Asia for the treatment of patients with haemophilia A. Although Biostate has been well characterized for FVIII and VWF (ratio 1:2 respectively) and shows a similar VWF multimeric pattern to normal plasma, limited published data is available on its clinical efficacy and safety in patients with von Willebrand disorder (VWD) who require surgical procedures. We retrospectively assessed the efficacy and safety of Biostate in all VWD patients treated at three Australian haemophilia treatment centres undergoing invasive procedures or surgery over a 29-month period between April 2003 and September 2005. A chart review of 43 VWD patients (26 VWD type 1, 12 VWD type 2, 5 VWD type 3; 21 male, 22 female; mean age 52 years, range 19-80 years) undergoing 58 surgical procedures (24 major, 34 minor) was performed. For each procedure, data were collected on Biostate dosage and administration, adverse reactions, haemostatic efficacy and bleeding events. Haemostatic efficacy of Biostate was assessed as excellent in 78% or good in 22% of procedures. There were no bleeding events attributable to lack of efficacy in any patients. No adverse reactions related to the administration of Biostate were observed. These results suggest that Biostate is both safe and efficacious for the prevention of excessive bleeding in VWD patients undergoing surgery or invasive procedures.
    No preview · Article · Apr 2007 · Haemophilia
  • A R Alhaliq · D Joshua · G Kershaw · S Dunkley

    No preview · Article · Mar 2007 · International Journal of Laboratory Hematology
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    ABSTRACT: Inhibitors are an uncommon complication of mild haemophilia A but represent a severe disease, typically with high titre inhibitors and an associated high rate of bleeding. We present data from three patients with MHAI who were successfully treated with Rituximab alone and unequivocally prove that such inhibitors respond to this agent. A treatment protocol is suggested.
    No preview · Article · Dec 2006 · Haemophilia
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    Full-text · Article · Apr 2006 · Journal of Thrombosis and Haemostasis
  • G Kidson-Gerber · A Bosco · S Maccallum · S Dunkley

    No preview · Article · Oct 2005 · Internal Medicine Journal
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    A Bosco · G Kidson-Gerber · S Dunkley

    Preview · Article · Jun 2005 · Journal of Thrombosis and Haemostasis
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    S Dunkley · A Street

    Preview · Article · Nov 2004 · Journal of Thrombosis and Haemostasis

Publication Stats

277 Citations
64.63 Total Impact Points


  • 1999-2015
    • Royal Prince Alfred Hospital
      • • Department of Anaesthetics
      • • Institute of Haematology
      Camperdown, New South Wales, Australia
  • 2005
    • South Eastern Area Laboratory Services
      Randwick, New South Wales, Australia
  • 2004-2005
    • Prince of Wales Hospital and Community Health Services
      Sydney, New South Wales, Australia