J Koutts

Westmead Hospital, Sydney, New South Wales, Australia

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Publications (90)439.75 Total impact

  • The Medical journal of Australia 03/2014; 200(5):293-294. DOI:10.5694/mja13.10921 · 4.09 Impact Factor
  • Ashraf Mina · Emmanuel J. Favaloro · Jerry Koutts
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    ABSTRACT: Deficiency of or defects in the plasma protein von Willebrand factor (VWF) lead to bleeding and von Willebrand disease (VWD), which may be congenital or acquired. VWD is considered the most common inherited bleeding disorder and laboratory testing for VWF level and activity is critical for appropriate diagnosis and management. We have designed and established a novel Flow Cytometry (FC) based method for measuring VWF antigen (VWF:Ag) and collagen binding (VWF:CB), together in the same tube and at the same time. The results of the novel FC method have been compared against existing reference methods using a range of normal and pathological material. Methods correlated well (VWF:Ag, r=0.866; VWF:CB, r=0.888) and generally permitted similar discrimination of quantitative versus qualitative VWD types (e.g. type 1 vs type 2A or 2B VWD). The novel procedure is expected to permit future streamlined performance of VWD screening, either using stand-alone FC systems or potentially incorporated into FC-capable automated blood cell and particle counters to allow for improved, automated and faster identification or exclusion of VWD.
    Thrombosis and Haemostasis 09/2012; 108(5). DOI:10.1160/TH12-05-0294 · 4.98 Impact Factor
  • Emmanuel J. Favaloro · Jerry Koutts
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    ABSTRACT: von Willebrand disease (VWD), which is the most common inherited bleeding disorder, arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into six types, with type 1 identifying a (partial) quantitative deficiency of VWF, type 3 defining a (virtual) total deficiency of VWF, and type 2 identifying four types (2A, 2B, 2M, and 2N) that are characterized by qualitative defects. The classification of VWD is based on phenotypic testing that includes factor VIII, VWF level, and VWF activity determined by ristocetin cofactor and/or collagen binding. Phenotypic testing may be supplemented by multimer analysis, ristocetin-induced platelet agglutination, and VWF:factor VIII binding. Although not required to diagnose VWD or for its classification, genetic analysis may be useful in discrete situations. The current review briefly covers this diagnostic process, with a focus on the newer approaches that include extended test panels and data from desmopressin challenges as a diagnostic tool.
    Laboratory Hematology Practice, 08/2012: pages 447-459; , ISBN: 9781405162180
  • Ashraf Mina · Emmanuel J Favaloro · Jerry Koutts
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    ABSTRACT: Short activated partial thromboplastin times (APTTs) are associated with thrombosis. However, what short APTTs actually represent in terms of possible mechanistic pathways is not well characterized. We have assessed thrombin generation as compared with levels of procoagulant factor (fibrinogen, V, VIII, IX, XI and XII) activities, von Willebrand factor level and activity using collagen binding, as well as procoagulant phospholipid activity, in 113 consecutive samples exhibiting a short APTT compared with an equal number of age-matched and sex-matched samples yielding a normal APTT. We found a significant difference in peak thrombin generation, velocity index and area under the curve between the two groups, and that thrombin generation markers correlated with the APTT, procoagulant phospholipid activity and several procoagulant clotting factors. We conclude that short APTTs represent a procoagulant milieu, as represented by heightened thrombin generation and several other heightened procoagulant activities, which may help explain the association with thrombosis.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 02/2012; 23(3):203-7. DOI:10.1097/MBC.0b013e32834fa7d6 · 1.40 Impact Factor
  • Source
    E J Favaloro · J Koutts
    Journal of Thrombosis and Haemostasis 12/2011; 10(2):317-9. DOI:10.1111/j.1538-7836.2011.04585.x · 5.72 Impact Factor
  • Ashraf Mina · Emmanuel J Favaloro · Jerry Koutts
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    ABSTRACT: Iodine deficiency disorders are due to inadequate thyroid hormone production and 2 billion individuals worldwide are estimated to have insufficient iodine intake. Laboratory assessment methods include urinary iodine (UI) concentration, blood FT3, FT4, TSH and Thyroglobulin. The aim of this study was to set up a robust method for testing urinary iodine using a microtitre robotic system. The UI method described is based on the Sandell-Kolthoff reaction, which utilizes the catalytic role of iodine in the reduction of ceric ammonium sulphate in the presence of arsenious acid. This method was automated for use on microtitre robotic system. The method was compared with the currently employed manual Sandell-Kolthoff reaction method in our laboratory as reference. The two methods correlated well using weighted Deming regression analysis (slope=1.066, intercept=6.5, r=0.994; n=211). Interassay and intraassay variations were similar to the reference method, but cost analysis indicated a large reduction in costs related to increased throughput, and reduced consumables and labour. We have successfully adapted UI testing to an automated method, permitting cheaper, faster and robust screening of large numbers of patients and populations. The described protocol can be used on different microtitre robotic systems permitting up to 372 patient samples per run for 4 microtitre plate systems.
    Journal of Trace Elements in Medicine and Biology 12/2011; 25(4):213-7. DOI:10.1016/j.jtemb.2011.09.001 · 2.37 Impact Factor
  • A. Mina · E. J. Favaloro · J. Koutts
    Laboratory Medicine 11/2011; 42(12):744-746. DOI:10.1309/LMALJBOWEF678RTD · 0.51 Impact Factor
  • Emmanuel J Favaloro · Giuseppe Lippi · Jerry Koutts
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    ABSTRACT: This review provides an update on laboratory testing and monitoring for existing and emerging anticoagulants, starting with an overview of haemostasis and the routine coagulation tests currently employed within most haemostasis laboratories, including the prothrombin time (PT)/international normalised ratio (INR) and the activated partial thromboplastin time (APTT). Current anticoagulant therapy and laboratory monitoring is then discussed in terms of benefits and limitations, followed by a similar brief discussion of the new and emerging anticoagulants. The main focus, however, is laboratory testing related to vitamin K antagonists, heparin, lepirudin and the new agents dabigatran etexilate and rivaroxaban. Although the newer agents do not require laboratory monitoring, laboratory testing will occasionally be required, and pathology laboratories should become proactive in developing appropriate strategies. The tests most likely to fulfill this role are the ecarin clotting time (or chromogenic alternatives), and the chromogenic anti-Xa assay. Nevertheless, the dilute Russell viper venom time (dRVVT) assay may provide another alternative, and existing routine tests are also likely to be utilised for the foreseeable future, potentially also for laboratory testing of the new anticoagulants, albeit perhaps in modified form.
    Pathology 11/2011; 43(7):682-92. DOI:10.1097/PAT.0b013e32834bf5f4 · 2.19 Impact Factor
  • E J Favaloro · C Forsyth · J Koutts
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    ABSTRACT: Discrimination of types 1 and 2M von Willebrand disease (VWD) is problematic. Type 1 VWD represents a quantitative deficiency of von Willebrand factor and type 2M a qualitative disorder. 2M VWD is considered a potentially more serious bleeding disorder than type 1 VWD and may also require a differential management approach given the higher bleeding risk and that desmopressin may be less effective. We describe a case of 2M VWD 'masquerading' as type 1 and show how the differential diagnosis can be obtained using standard laboratory assays. The case was genetically confirmed as a 3943C>T mutation, leading to R1315C.
    International journal of laboratory hematology 07/2011; 34(1):102-5. DOI:10.1111/j.1751-553X.2011.01362.x · 1.82 Impact Factor
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    ABSTRACT: Von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein Von Willebrand factor (VWF). VWD is classified into six different types, with type 1 identifying a (partial) quantitative deficiency of VWF, type 3 defining a (virtual) total deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, and 2N) characterized by qualitative defects. The classification is based on phenotypic assays including factor VIII coagulant, VWF antigen, and VWF activity, primarily by ristocetin cofactor and collagen binding, as supplemented by additional testing. In Australia, >30 pathology-based laboratories perform VWD testing, and tests and test panels reflect a wide variety of practice. In our own referral laboratory, diagnosis is a staged process reflecting a combination of clinical and laboratory findings with a large panel of tests. We also use data from desmopressin trials to assist in VWD type assignment. The current report presents an overview of the VWD diagnostic process as applied within Australia, includes summary data from the Australian Bleeding Disorders Registry, and provides specific details of the diagnostic and management practice undertaken in our reference laboratory, which also maintains a local bleeding disorders database. This database currently contains 4070 entries, including 1832 suspected or confirmed cases of VWD. Excluding 311 as yet unclassified cases, 1254 cases (82.4%) would define (potential) quantitative deficiencies of VWF ("low VWF" or type 1 VWD), 241 (15.8%) qualitative defects (type 2 VWD), and 23 (1.5%) type 3 VWD. Most of the quantitative defects reflect only mild loss of VWF, and <15% of total cases would be identified to have VWF levels <35 U/dL. Most cases of type 2 remain unclassified (34.9%) because available data are limited. Type 2A and 2M VWD represent the most common qualitative defects, representing 22.8% and 22.2% of defined type 2 VWD cases. Type 2B and 2N reflect 8.3% and 12.9%, respectively, of type 2 VWD cases.
    Seminars in Thrombosis and Hemostasis 07/2011; 37(5):542-54. DOI:10.1055/s-0031-1281041 · 3.88 Impact Factor
  • Pathology 01/2011; 43(1):75-8. DOI:10.1097/PAT.0b013e3283419ec1 · 2.19 Impact Factor
  • E. J. Favaloro · R. Reben · S. Mohammed · J. Koutts
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    ABSTRACT: Background: The antiphospholipid syndrome (APS) is an autoimmune condition characterised by vascular thromboses and/or pregnancy morbidity. Diagnosis of APS typically requires laboratory evidence of antiphospholipid antibodies (aPL). Depending on their clinical presentation, affected individuals might be seen by a variety of clinical specialities. Aim: To evaluate clinical ordering patterns for aPL/APS at a tertiary level public facility. Methods: We performed an audit of internal clinical requests for aPL tests at our institution for a 6-month period. Results: We identified a wide variety of clinical ordering background for aPL, of predominantly obstetric (72/268; 26.9%) or thrombophilic (78/268; 29.1%) patients. Only 11/268 samples (4.1%) were positive for lupus anticoagulant (LA) and 14/268 (5.2%) were positive for anticardiolipin antibody (aCL). The percentage of aCL positivity in the LA-positive group was 46% (5/11). None of the 72 obstetric patients tested was identified to have aPL. Of the 11 LA-positive patients, the reasons identified for testing comprised: prolonged Activated Partial Thromboplastin Time (assay) (n= 3), thrombosis (n= 3), APS (n= 2), systemic lupus erythematosus (n= 2), vasculitis (n= 1). Conclusion: We determined a wide variety of clinical ordering background for aPL at a tertiary level institution, with an overall low rate (<10%) of aPL positivity among a hospital population of predominantly obstetric or thrombophilic patients. That no positive obstetric aPL cases were identified suggests local clinical ordering guidelines may need review, as also potentially practised at other institutions. We also observed a moderate rate (46%) of coincidence of aCL and LA, in agreement with guidelines indicating that multiple tests are required to identify APS.
    Internal Medicine Journal 07/2010; 42(4):427 - 434. DOI:10.1111/j.1445-5994.2010.02329.x · 1.64 Impact Factor
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    ABSTRACT: Although short activated partial thromboplastin times (APTTs) are generally considered to be laboratory artefacts of problematic blood collections, there is mounting evidence that in some cases a short APTT may reflect a hypercoagulable state, potentially associated with increased thrombotic risk and adverse cardiovascular events. We prospectively evaluated the phenomenon of short APTTs in 113 consecutive samples compared with an equal number of age and sex-matched normal APTT samples. We found a significant difference in various test parameters including prothrombin time (PT), Factor (F) V, FVIII, FXI, FXII, von Willebrand factor (VWF) antigen and collagen-binding activity, and in the level of procoagulant phospholipids, as assessed using a novel assay procedure (XACT). Interestingly, there was a significant negative association for fibrinogen, and although elevated, there was no significant association for FIX. On the basis of identified consecutive samples having multiple low APTTs on several sequential days, a proportion of laboratory-defined short APTTs appear to represent in-vivo hypercoagulability. In conclusion, plasma from patients presenting with short APTTs is reflective of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, and 20% or more of laboratory definable short APTTs appear to reflect in-vivo phenomenon.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 03/2010; 21(2):152-7. DOI:10.1097/MBC.0b013e3283365770 · 1.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into six different types, with Type 1 identified as a (partial) quantitative deficiency of VWF, Type 3 a (virtually) total deficiency of VWF, and Type 2 identifying four separate types (2A, 2B, 2M, 2N) characterized by qualitative defects. The classification is currently based on phenotypic assays, supplemented by multimeric analysis of the von Willebrand protein. Although genetic analysis is not required in order to diagnose VWD or to define a patient's VWD classification type, genetic analysis may be useful in discrete situations, in order to confirm or assist the diagnosis. In particular, genetic analysis may be useful in: (i) Type 2N VWD (primarily as an aid to discriminate this from hemophilia A/carrier); (ii) Type 2B VWD (primarily as an aid to discriminate this from PT-VWD); (iii) Type 3 VWD (for prenatal assessment/family studies and alloantibody risk assessment); and perhaps also in (iv) other Type 2 VWD investigations; and (v) very select Type 1 VWD investigations (eg, VWF levels are B25 IU/mL, or family studies where causative mutation is already known). However, genetic testing should not be used as a surrogate for a poor phenotypic test approach, and it is important that a thorough phenotypic workup be applied prior to requesting genetic testing in VWD.
    Journal of Coagulation Disorders 01/2010; 2.
  • Emmanuel J Favaloro · Soma Mohammed · Jerry Koutts
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    ABSTRACT: We report an investigation of type 2N von Willebrand disease (VWD), covering the past 7 years and evaluating 1031 plasma samples from over 500 patients. Samples included specific requests for investigation of possible type 2N VWD (including family studies) and samples from 'hemophilia' or nonspecified VWD investigations that could unknowingly be type 2N VWD. In total, 13 new patients with type 2N VWD were identified, four of whom initially presented with normal levels of factor VIII and only three of whom (i.e. 23%) derived from specific clinical requests for investigation of type 2N VWD. Furthermore, type 2N VWD was excluded in 91% of specific clinical requests for type 2N VWD investigations. Poststudy evaluation indicates that type 2N VWD in this geographic region has an incidence rate similar to that in other westernized regions, accounting for around 1-2% of all identified VWD cases and about 13% of all type 2 VWD cases. In conclusion, this study highlights that clinicians requesting laboratory investigations related to a bleeding tendency often fail to appropriately recognize the possibility of type 2N VWD, that a normal plasma factor VIII will not exclude type 2N VWD, and although a relatively uncommon form of VWD overall, type 2N VWD represents a significant qualitative disorder.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 10/2009; 20(8):706-14. DOI:10.1097/MBC.0b013e328332d022 · 1.40 Impact Factor
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    ABSTRACT: We performed a retrospective audit of cross-laboratory testing of desmopressin and factor concentrate therapy to assess the potential utility of supplementary testing using the PFA-100 with functional von Willebrand factor (VWF) activity testing. Data were evaluated for a large number of patients with von Willebrand disease of type 1, type 2A or type 2M, as well as a comparative subset of individuals with haemophilia or carriers of haemophilia. Laboratory testing comprised pre and postdesmopressin, or pre and postconcentrate, evaluation of factor VIII, VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity as traditionally performed, supplemented with collagen-binding (VWF:CB) testing and PFA-100 closure times. In brief, both therapies tended to normalize VWF test parameters and closure times in individuals with type 1 von Willebrand disease, with the level of correction in closure times related to the level of normalization of VWF, particularly the VWF:CB. However, although occasional correction of closure times was observed in patients with type 2A or type 2M von Willebrand disease, these did not in general normalize PFA-100 closure times either with desmopressin or factor concentrate therapy. In these patients, improvement in closure times was more likely in those in whom VWF:CB values normalized or when VWF:CB/VWF:Ag ratios normalized. This study confirms that there is a strong relationship between the presenting levels of plasma VWF and PFA-100 closure times, and that the supplementary combination of PFA-100 and VWF:CB testing might provide added clinical utility to current broadly applied testing strategies limited primarily to VWF:Ag, VWF ristocetin cofactor and factor VIII:coagulant. Future prospective investigations are warranted to validate these relationships and to investigate their therapeutic implications.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 08/2009; 20(6):475-83. DOI:10.1097/MBC.0b013e32832da1ad · 1.40 Impact Factor
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    ABSTRACT: PURPOSE. To determine whether associations exist between cataract and established cardiovascular risk factors (other than smoking) – hypertension, body mass index, serum lipids and plasma fibrinogen. METHODS. The Blue Mountains Eye Study is a large (n=3654) population-based cross-sectional study conducted among people aged 49-97 years residing in the Blue Mountains, a region west of Sydney, Australia. Risk factor data were collected using standardised clinical procedures. Lens photographs were taken and graded for presence and severity of cortical, nuclear, and posterior subcapsular cataracts. RESULTS. Cortical cataract was associated with a history of myocardial infarction, higher plasma fibrinogen, and higher serum cholesterol. Nuclear cataract was associated with a higher platelet count but hypertension was associated with lower prevalence of nuclear cataract. Posterior subcapsular cataract was associated with higher plasma fibrinogen and lower body mass index. Some of these associations appeared to be stronger in women than in men: fibrinogen and cortical cataract and body mass index and posterior subcapsular cataract. CONCLUSIONS. Several risk factors for cardiovascular disease are associated with presence of cataract, perhaps explaining the observation in several studies that people with cataract have increased mortality rates. The possibility of strong associations between plasma fibrinogen and cataract merits further epidemiological and laboratory research.
    Ophthalmic Epidemiology 07/2009; 6(4):279-290. DOI:10.1076/opep. · 1.15 Impact Factor
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    ABSTRACT: Fifty-four adolescent and adult patients with newly-diagnosed acute lymphoblastic leukaemia (ALL) were treated with combination chemotherapy at three Australian hospitals. The protocol consisted of one month of induction therapy with five cytotoxic agents, followed by consolidation therapy and prophylactic treatment to the central nervous system, then maintenance chemotherapy for 30 months on an outpatient basis. Complete remission was achieved in 47 (87%) patients, with 5 deaths due to treatment-related toxicity. Two patients had drug-resistant disease. Twenty-two patients subsequently relapsed in the bone marrow (18) or in the central nervous system (4). The median survival for all 54 patients is 45.6 months, while the median duration of remission for the 47 complete responders is 39.0 months, with 38.1% projected to be disease-free at 5 years. Age at diagnosis was found to be the only parameter at presentation with a significant predictive effect on outcome. Patients between 10 and 20 years of age had a median survival of 120.6 months, with the median duration of remission not yet reached. In contrast, patients aged 20 years or more had a significantly poorer outcome, with median survival and remission of 25.8 and 20.8 months respectively. These results would support the use of intensive chemotherapy for adolescent patients with ALL. The poor results in adults however justify the use of alternative approaches such as bone marrow transplantation.
    Leukemia and Lymphoma 06/2009; 4(5-6):317-324. DOI:10.3109/10428199109068081 · 2.89 Impact Factor
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    ABSTRACT: We performed a retrospective audit of desmopressin (DDAVP) usage to assist in the functional characterisation of von Willebrand disease (VWD). Data was evaluated for 208 patients, comprising those with VWD (Type 1 [n=160], Type 2A [n=19], Type 2M [n=10]), plus 19 individuals with haemophilia or carriers of haemophilia. Laboratory testing comprised pre- and post-DDAVP evaluation of factor VIII (FVIII:C), von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo) activity, VWF collagen binding (VWF:CB) activity, and in one laboratory an alternate VWF activity assay. In brief, combined usage of VWF:RCo and VWF:CB appears to provide improved functional characterisation and/or 'classification' of VWD types, in particular better differentiation of Type 2A and 2M VWD, and clearer validation of a Type 1 VWD diagnosis. Thus, (i) Type 1 VWD displayed generally good absolute and relative rises in all test parameters, although relative rises were greatest for FVIII:C and VWF:CB, and CB/Ag ratio increases overshadowed those for RCo/Ag; (ii) Type 2A VWD patients showed good absolute and relative rises in both FVIII:C and VWF:Ag, but poor absolute rises in both VWF:CB and VWF:RCo; although small rises in both CB/Ag and RCo/Ag were also observed, both ratios tended to remain below 0.7; (iii) finally, Type 2 M VWD patients generally showed good absolute and relative rises in FVIII:C, VWF:Ag and VWF:CB, but a poor absolute and relative rise in VWF:RCo; thus, there were good rises in CB/Ag ratios but little change in RCo/Ag, which tended to remain below 0.7. Future multi-centre prospective investigations are warranted to validate these findings and to investigate their therapeutic implications.
    Thrombosis Research 04/2009; 123(6):862-8. DOI:10.1016/j.thromres.2008.10.008 · 2.45 Impact Factor
  • Ashraf Mina · Emmanuel J Favaloro · Jerry Koutts
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    ABSTRACT: In response to increasingly complex demands in terms of productivity and budgets, there is a critical need to avoid mistakes during instrument selection that will be financially costly, and adversely affect customers, staff, productivity and test turnaround time. As there is no “one size fits all”, guidelines must be appropriate to permit informed decision making. A Medline search was conducted to assess background knowledge in this area, using the terms “laboratory instrument selection” and “laboratory instrument evaluation”. Searches returned over 800 articles, of which only seven were directly related to the topic of the search, with most outdated, and suggesting a paucity of appropriate information. Additional resources used included the American Association of Clinical Chemistry (AACC) website and the Internet. Appropriate criteria for instrument selection were established in the current report based on subjective and objective (technical) evaluations. Additionally, a sound and simple financial approach is also suggested to help in making informed decisions and avoid costly mistakes. We propose that such a process as outlined in our report will protect laboratories from making costly and avoidable mistakes in the acquisition of major equipment. Clin Chem Lab Med 2008;46:1223–9.
    Clinical Chemistry and Laboratory Medicine 08/2008; 46(9):1223-9. DOI:10.1515/CCLM.2008.264 · 2.71 Impact Factor

Publication Stats

1k Citations
439.75 Total Impact Points


  • 1984–2012
    • Westmead Hospital
      • • Department of Haematology
      • • Institute of Clinical Pathology and Medical Research
      Sydney, New South Wales, Australia
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2000
    • The University of the West Indies at Mona
      • Department of Medicine
      Kingston, Kingston, Jamaica
  • 1992
    • University of Newcastle
      Newcastle, New South Wales, Australia
  • 1974–1985
    • Alfred Hospital
      • Department of Haematology
      Melbourne, Victoria, Australia
  • 1974–1981
    • Monash University (Australia)
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 1975
    • University of Melbourne
      Melbourne, Victoria, Australia