Real-world decision-making in the management of patients presenting with major bleeding on rivaroxaban: the Auckland regional experience.

Background: Rivaroxaban is used increasingly as an oral anticoagulant; however, a specific reversal agent is not currently available in the Australasian setting. There is also variation across international consensus guidelines regarding advice on the management of bleeding.

Aims: To review the real-world management of rivaroxaban-associated major bleeding across the public hospitals of New Zealand's largest city.

Real-world experience with limited screening for occult malignancy in patients presenting with spontaneous venous thromboembolism: a single-centre, retrospective cohort study.

Spontaneous venous thromboembolism (VTE) may represent the first manifestation of previously undiagnosed malignancy; however, contemporary international guidelines call for a limited approach to screening for malignancy in such patients. This retrospective cohort study of 328 patients presenting to the Auckland City Hospital Thrombosis Unit identified 17 patients who were subsequently diagnosed with some form of malignancy within 12 months of their presentation. Review of their history, physical examination and limited age and gender-appropriate cancer screening investigations as described by the National Institute for Clinical Excellence and International Society of Thrombosis and Haemostasis guidelines revealed that all 17 would have been safely diagnosed by the 'limited' screening approach endorsed by these guidelines, thus presenting a 'real-world' basis for clinicians to pursue 'limited' screening for malignancy in their everyday practice in patients with spontaneous VTE.

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study).

Background: Treatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain.

Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT.

Primary Outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group.

Diagnosis and treatment of RD in an Australasian cohort with thrombocytopenia.

-related disorders (-RDs) caused by mutation of the gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy.

Challenges in hemophilia care in Australia and New Zealand.

Background: Health and life expectancy for people with hemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services.

Aim: This paper aims to highlight such challenges and propose practical solutions.

Methods: Nine hemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in hemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these.

Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study.

Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study.

The use of a co-design model in improving timely bleed reporting by adults with haemophilia living in the Auckland region of New Zealand.

Many adult patients diagnosed with phenotypically moderate and severe haemophilia living in the Auckland region of New Zealand do not report bleeding episodes within a timeframe that allows for optimal assessment and management. This can result in poor clinical outcomes for patients and poor oversight of the use of expensive clotting factor concentrates. Our goal was to improve both the number and speed at which bleeding episodes were reported to our centre, improving access to care and clinical oversight of the use of expensive factor concentrates and aiding the development of a care partnership with patients.

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors. Working group of hematology experts from Australia and New Zealand, Melbourne, April 2011.

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.

Low-dose aspirin for preventing recurrent venous thromboembolism.

Background: Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism.

Methods: We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years.

Two missense mutations identified in venous thrombosis patients impair the inhibitory function of the protein Z dependent protease inhibitor.

Protein Z-dependent protease inhibitor (ZPI) is a plasma inhibitor of factor (F)Xa and FXIa. In an earlier study, five mutations were identified within the ZPI gene of venous thrombosis patients and healthy controls. Two of these were nonsense mutations and three were missense mutations in important regions of the protein.

Survival in patients with malignancy and venous thromboembolism by tumour subtype and thrombus location.

Background: Although the association between malignancy and venous thromboembolism (VTE) is firmly established, less is known about the survival following VTE among different malignant subtypes.

Aims: We sought to estimate survival from first VTE in consecutive patients with known malignancy receiving extended low molecular weight heparin therapy.

Methods: Five hundred and fifty-nine consecutive patients presenting to the Thrombosis Unit Registry at Auckland City Hospital between January 1997 and October 2006 were observed.

Posttreatment ultrasound-detected residual venous thrombosis: a risk factor for recurrent venous thromboembolism and mortality.

Purpose Of Review: The cumulative risk of recurrent venous thrombosis may rise to 30% over 8 years. Extended oral anticoagulation is effective but major bleeding is increased. To balance these risks attention has focused on identifying patients with the highest likelihood of recurrence for whom continued therapy is most beneficial.

D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly.

Background: The D-dimer assay is used as an exclusion test in the assessment of suspected venous thromboembolic disease; patients with a negative result have a low probability of thrombosis. We reviewed the D-dimer results from a hospital and community laboratory using the vidas D-dimer test to assess the influence of age on the D-dimer assay.

Methods: D-dimer results from 6631 unselected patients aged more than 16 years were analysed in four age groups and it was shown that the median D-dimer concentration increased with age (16-40 years, 294 ng/mL; 40-60 years, 387 ng/mL; 60-80 years; 854 ng/mL; >80 years, 1397 ng/mL).

Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism.

Context: When unfractionated heparin is used to treat acute venous thromboembolism, it is usually administered by intravenous infusion with coagulation monitoring, which requires hospitalization. However, subcutaneous administration of fixed-dose, weight-adjusted, unfractionated heparin may be suitable for inpatient and outpatient treatment of venous thromboembolism.

Objective: To determine if fixed-dose, weight-adjusted, subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for treatment of venous thromboembolism.

Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality.

Background: Recurrent thromboembolic events after an initial deep vein thrombosis (DVT) are relatively frequent. Residual thrombus in the affected veins on ultrasound scan at the completion of anticoagulant therapy has been described as a recurrence risk factor, and may have utility in stratifying those patients at risk.

Objectives: The aims of the study were to correlate the risk of recurrence of DVT with the results of ultrasound at completion of oral anticoagulant therapy.

Audit of community-based anticoagulant monitoring in patients with thromboembolic disease: is frequent testing necessary?

Oral anticoagulant monitoring is managed by general practitioners in Auckland. An audit of this service in 452 patients demonstrated that anticoagulant control was in line with recommended international guidelines, with 58.3% of international normalized ratio (INR) measurements in the therapeutic range.

Mutations within the protein Z-dependent protease inhibitor gene are associated with venous thromboembolic disease: a new form of thrombophilia.

Protein Z-dependent protease inhibitor (ZPI) is a serpin that inhibits the activated coagulation factors X and XI. The precise physiological significance of ZPI in the control of haemostasis is unknown although a deficiency of ZPI may be predicted to alter this balance. The coding region of the ZPI gene was screened for mutations using denaturing high-performance liquid chromatography.

The challenge arising from the cost of haemophilia care: an audit of haemophilia treatment at Auckland Hospital.

Aims: To compare treatment patterns in adults and children with haemophilia and to estimate the financial impact of the changing practice of haemophilia care.

Methods: A retrospective audit of replacement coagulation factor usage in all patients with haemophilia treated at the Auckland Haemophilia Centre during 2001.

Results: A total of 69 males with haemophilia were included in the audit.

Novel fibrinogen truncation with deletion of Bbeta chain residues 440-461 causes hypofibrinogenaemia.

A 24-year-old male with hepatitis C was initially diagnosed with hypofibrinogenaemia during investigations prior to a liver biopsy. He had a low functional and gravimetric fibrinogen concentration of 1.0 mg/mL and DNA sequencing of all exons, exon-intron boundaries and promoter regions of the fibrinogen Aalpha, Bbeta, and gamma genes revealed a single heterozygous g-->a mutation at nucleotide 8035 of the Bbeta gene.

The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes.

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control.