S Dunkley

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

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Publications (22)60.32 Total impact

  • [Show abstract] [Hide abstract]
    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.
  • 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.
    Haemophilia 07/2014; 20(4):e275-9. DOI:10.1111/hae.12442 · 2.47 Impact Factor
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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.
    Vox Sanguinis 04/2014; DOI:10.1111/vox.12121 · 3.30 Impact Factor
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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.
    Internal Medicine Journal 11/2012; 42(11):1243-50. DOI:10.1111/j.1445-5994.2012.02942.x · 1.70 Impact Factor
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    ABSTRACT: INTRODUCTION: 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. METHODS: 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. RESULTS: In our study, we showed the ability of FEIBA(®) to improve the abnormal thrombin generation parameters caused by dabigatran in these patients. CONCLUSION: This provides evidence, lacking in the literature, that this agent may be able to provide haemostatic support in situations where dabigatran induced coagulopathy exists.
    International journal of laboratory hematology 09/2012; 35(2). DOI:10.1111/ijlh.12005 · 1.87 Impact Factor
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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.
    Haemophilia 03/2010; 16(4):615-24. DOI:10.1111/j.1365-2516.2010.02206.x · 2.47 Impact Factor
  • Injury 02/2009; 40. DOI:10.1016/j.injury.2009.01.087 · 2.46 Impact Factor
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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.
    Internal Medicine Journal 04/2008; 38(3):156-65. DOI:10.1111/j.1445-5994.2007.01472.x · 1.70 Impact Factor
  • ISBT Science Series 11/2007; 2(2):110-112. DOI:10.1111/j.1751-2824.2007.00123.x
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    S Dunkley, L Gaudry
    Journal of Thrombosis and Haemostasis 07/2007; 5(6):1323-5. DOI:10.1111/j.1538-7836.2007.02542.x · 5.55 Impact Factor
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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.
    Haemophilia 04/2007; 13(2):144-8. DOI:10.1111/j.1365-2516.2006.01430.x · 2.47 Impact Factor
  • International Journal of Laboratory Hematology 03/2007; 29(1):69-70. DOI:10.1111/j.1365-2257.2006.00849.x · 1.87 Impact Factor
  • Heart, Lung and Circulation 01/2007; 16. DOI:10.1016/j.hlc.2007.02.051 · 1.17 Impact Factor
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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.
    Haemophilia 12/2006; 12(6):663-7. DOI:10.1111/j.1365-2516.2006.01351.x · 2.47 Impact Factor
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    Journal of Thrombosis and Haemostasis 04/2006; 4(3):678-9. DOI:10.1111/j.1538-7836.2006.01829.x · 5.55 Impact Factor
  • Internal Medicine Journal 10/2005; 35(9):569-70. DOI:10.1111/j.1445-5994.2005.00905.x · 1.70 Impact Factor
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    A Bosco, G Kidson-Gerber, S Dunkley
    Journal of Thrombosis and Haemostasis 06/2005; 3(5):1109-10. DOI:10.1111/j.1538-7836.2005.01296.x · 5.55 Impact Factor
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    S Dunkley, A Street
    Journal of Thrombosis and Haemostasis 11/2004; 2(10):1852-3. DOI:10.1111/j.1538-7836.2004.00846.x · 5.55 Impact Factor
  • S Dunkley
    Internal Medicine Journal 01/2004; 33(12):623-4; author reply 624. DOI:10.1111/j.1445-5994.2003.00502.x · 1.70 Impact Factor
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    Journal of Thrombosis and Haemostasis 11/2003; 1(10):2248-50. DOI:10.1046/j.1538-7836.2003.00429.x · 5.55 Impact Factor

Publication Stats

229 Citations
60.32 Total Impact Points

Institutions

  • 1998–2015
    • 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