Circulating microvesicles in snakebite patients with microangiopathy.

Background: Venom-induced consumption coagulopathy is a common consequence of snake envenoming that can lead to life-threatening hemorrhage, and is associated with microangiopathic hemolytic anemia (MAHA), acute kidney injury and thrombocytopenia. The role of microvesicles (MV) in snakebite patients has not been previously investigated.

Objective: To compare changes in subsets of circulating MV levels in snakebite patients with venom induced consumption coagulopathy and with or without microangiopathic hemolysis to those of healthy controls.

Circulating microvesicles are less procoagulant and carry different miRNA cargo in myelodysplasia.

Background And Aims: Myelodysplasia (MDS) is characterised by abnormal haematopoiesis and increased risk of bleeding. Microvesicles (MV) play a key role in coagulation and their impact in MDS is unknown.

Methods: Platelet free plasma from 35 red-cell transfusion-dependent MDS patients and 15 controls were analysed.

Circulating microvesicle number, function and small RNA content vary with age, gender, smoking status, lipid and hormone profiles.

Background: Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied.

Objectives: We evaluated the influence of age, gender, smoking status, lipid and hormone profiles on circulating MV in healthy subjects.

Methods: Platelet free plasma from 143 volunteer blood donors (males=80, females=63) was evaluated by standardized flow cytometry for MV expressing CD41 (platelet-derived), CD105 (endothelial-derived), CD235 (red cell-derived), TF (tissue factor) and phosphatidylserine (PS) MV.

Correlative analysis of nanoparticle tracking, flow cytometric and functional measurements for circulating microvesicles in normal subjects.

Introduction: Circulating microvesicles (MV) can be analysed using a number of different techniques. The aim of this study was to evaluate the correlation between functional procoagulant based assays including thrombin generation, factor Xa activation test (XaCT), and phosphatidylserine factor Xa-activity by ELISA with optical MV enumeration by flow cytometry and nanoparticle tracking analysis.

Methods: Citrated blood samples were collected from 60 healthy volunteer blood donors after informed consent.

Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

Background: Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy.

Methods: Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study.

Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: a randomised controlled study.

Background: LCn-3PUFA comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer cardioprotection involving a decrease in coagulant activity; however, the evidence is equivocal. We have previously demonstrated that the acute (24 h) effects and chronic (4 weeks) effects of LCn-3PUFA supplementation on platelet aggregation in human subjects are sex specific. This study investigated the mechanisms of the sex-dependent effects of LCn-3PUFA with 4 weeks supplementation of EPA-rich vs.

Comparative sensitivity of commercially available aPTT reagents to mulga snake (Pseudechis australis) venom.

This study aimed to determine the relative sensitivity of activated partial thromboplastin time (aPTT) reagents to the anticoagulant effects of phospholipases in mulga snake (Pseudechis australis) venom.Twenty-one haematology laboratories participating in the Royal College of Pathologists of Australasia Quality Assurance Programs were sent human plasma samples spiked with mulga venom (n=25 total results). Results for 17 patients with mulga snake envenoming were available through the Australian Snakebite Project.

An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: long-term results of the CMLALL1 trial.

We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCR-ABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens.

Health of adults living with a clinically significant haemoglobinopathy in New South Wales, Australia.

Aim: To comprehensively review the health needs of patients living with clinically significant haemoglobinopathies (thalassaemia and sickle-cell disease (SCD)) in New South Wales, Australia.

Methods: A survey-based health needs assessment was undertaken in outpatients cared for at five tertiary institutions in metropolitan and regional centres. Sixty-three of 121 adults (approximately 80-90% of adult patients with transfusion-requiring haemoglobinopathies in New South Wales) completed an in-house and commercial health-related quality assessment survey (SF-36v2).

A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18).

Background: Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming.

Objectives: To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation.

Patients/methods: This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs.

All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4).

The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome.

Implications of a needs assessment intervention for people with progressive cancer: impact on clinical assessment, response and service utilisation.

Objective: To assess the impact of the systematic use of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease-Cancer (NAT: PD-C) on clinical assessment, response and service utilisation.

Study Setting: Three major oncology treatment centres in NSW, Australia.

Study Design: Between March 2007 and December 2009, 219 people with advanced cancer were recruited to complete bi-monthly telephone interviews.

Thrombotic microangiopathies, thrombotic thrombocytopenic purpura, and ADAMTS-13.

Thrombotic microangiopathy (TMA) is a term used to describe a group of disorders characterized by hemolytic anemia (with prominent red blood cell fragmentation), thrombocytopenia, and thrombosis in the microvasculature. It may be used when describing patients with thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, atypical hemolytic uremic syndrome, as well as a myriad of other disorders in which the TMA may be secondary to another disease or disorder. While limited information exists as to the exact cause of microthrombosis in many TMA, recent advances have been made in the understanding of TTP and its pathophysiology.

Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects.

Background: Dietary supplementation with omega-3 fatty acids has been associated with reduced incidence in thrombotic events. In addition, administration of n-3 polyunsaturated fatty acids (PUFAs) has been shown to rectify elevated platelet microparticle (MP) number and procoagulant activity in post myocardial infarction patients. However, it is unknown whether supplementation can alter these parameters in healthy individuals and if such effects are immediate or require long-term supplementation.

Variable plasma levels of Factor V Leiden correlate with circulating platelet microparticles in carriers of Factor V Leiden.

Introduction: Inheritance of Factor V Leiden (FVL) is associated with an increased but variable level of risk for thrombosis. We have previously shown that FVL heterozygotes have elevated levels of circulating pro-coagulant microparticles (MP). Here we sought to determine if these subjects differed in their plasma levels of FVL and if this was related to MP concentrations and/or history of thrombosis.

The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene.

Aims: To investigate whether polymorphisms of the cyclo-oxygenase-2 (COX-2) gene modify the adverse cardiovascular effects of COX-2 inhibitors.

Methods: A case control study was conducted in the Hunter Region of New South Wales, Australia. Cases (n= 460) were hospitalized with acute coronary syndrome (ACS).

The clinical efficacy and safety of the FVIII/VWF concentrate, BIOSTATE®, in children with von Willebrand disorder: a multi-centre retrospective review.

Factor replacement with BIOSTATE(®), a factor VIII (FVIII)/von Willebrand factor concentrate, forms the mainstay of treatment for children with von Willebrand disorder (VWD) in Australia and New Zealand. However, published data on the clinical efficacy and safety of BIOSTATE in the VWD paediatric population are limited. We retrospectively assessed the efficacy and safety of BIOSTATE in 43 children with VWD who received treatment for surgery, non-surgical bleeds or continuous prophylaxis at eight paediatric haemophilia centres in Australia and New Zealand.

Factor deficiencies in venom-induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10).

Background: Limited information exists on the dynamics of hemostasis in patients with venom-induced consumption coagulopathy (VICC) from snake envenomation.

Objective: The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation.

Methods: We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study.

Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom.

Venom-induced consumption coagulopathy occurs in snake envenoming worldwide but the interaction between procoagulant snake venoms and human coagulation remains poorly understood. We aimed to evaluate an assay using endogenous thrombin potential (ETP) to investigate the procoagulant properties of a range of Australian whole venoms in human plasma and compared this to traditional clotting and prothrombinase activity studies. We developed a novel modification of ETP using procoagulant snake venoms to trigger thrombin production.

Clinical efficacy and safety of the factor VIII/von Willebrand factor concentrate BIOSTATE in patients with von Willebrand's disease: a prospective multi-centre study.

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.

Circulating microparticles are elevated in carriers of factor V Leiden.

Introduction: Microparticles (MP) are small membrane bound cellular particles that play an important role in thrombosis. This study was carried out to evaluate if increased numbers or procoagulant potential of circulating MP contribute to the heterogeneity in occurrence of thrombosis in heterozygotes carrying Factor V Leiden (FVL) mutation.

Methods: Levels of circulating platelet (CD41a), endothelial (CD62e) as well as leukocyte (CD45) derived MP from 45 FVL heterozygous individuals were enumerated by flow cytometry and compared with normal controls.

Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase.

Host colonisation by lymphotropic gammaherpesviruses depends critically on the expansion of viral genomes in germinal centre (GC) B cells. Yet, host and virus molecular mechanisms involved in driving such proliferation remain largely unknown. Here, we show that the ORF73 protein encoded by the murid herpesvirus-4 (MuHV-4) inhibits host nuclear factor-kappa B (NF-kappaB) transcriptional activity through poly-ubiquitination and subsequent proteasomal-dependent nuclear degradation of the NF-kappaB family member p65/RelA.