Thrombosis in patients with immune thrombocytopenia: incidence, risk, and clinical outcomes.

Background: There is evidence that patients with immune thrombocytopenia (ITP) are at increased risk of thrombosis. However, the association of clinical- and treatment-related factors with thrombosis remains controversial. Objectives: To evaluate the incidence and impact of risk factors for arterial and venous thromboembolism (VTE) in patients with ITP and characterize the clinical features and management of patients. Methods: We performed a retrospective cohort study (January 1, 2011, to October 30, 2022) of adult patients diagnosed with ITP from an Australian tertiary hospital. The incidence rates of thrombosis were calculated in terms of person-years of follow-up. Multiadjusted Cox regression was used to estimate associations. Results: A total of 220 patients with 1365 person-years of follow-up since ITP diagnosis revealed 26 (11.8%) patients with a total of 37 thrombosis events, 29 (78%) VTE and 8 (22%) arterial thromboembolism (ATE). The incidence rate of thrombosis was 2.71 (95% CI, 1.97-3.72) (0.66 [95% CI, 0.33-1.26] for arterial thromboembolism and 2.05 [95% CI, 1.42-2.95] for VTE) per 100 person-years. Mean age and median time to first thrombosis diagnosis was 56 and 2.13 years, respectively. Age, secondary ITP, lines of therapy, thrombosis risk factors, and thrombopoietin receptor agonist therapy were independently associated with thrombosis. Almost all patients (25 of 26, [96%]) had good ITP disease control prior to thrombosis diagnosis, and antithrombotic therapy was deliverable and well tolerated. Conclusion: Diagnosis of thrombosis in patients with ITP, while infrequent, is of clinical significance. We identified from a heterogeneous real-world cohort that older patients with multiply-treated secondary ITP receiving thrombopoietin receptor agonists are at the highest risk.

Between a rock and a hard place: resumption of oral anticoagulant therapy after intracranial hemorrhage.

Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation.

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. METHODS: A retrospective cohort analysis was performed of patients prescribed rivaroxaban who presented to four metropolitan hospital Emergency Departments between 1 August 2018 and 31 May 2021 with major bleeding as defined by the International Society on Thrombosis and Haemostasis. RESULTS: One hundred and twelve patients were identified, accounting for 115 major bleeding presentations. Upper gastrointestinal (34%) and intracranial (31%) bleeding sites were most common. Procedural intervention was required in 44% of patients. Haemostatic management involved tranexamic acid (TXA) in 26%, prothrombin complex concentrate (PCC) in 55% (dose range 1000-6000 IU or 10-65 IU/kg), vitamin K in 16% and fresh frozen plasma in 1%. Rivaroxaban was discontinued permanently following 56 (49%) events, switched to another anticoagulant in 24 (21%) and withheld in 30 (26%) from 2 days to 3 months (median 8.5 days). All-cause mortality at 90 days after bleeding was 17% (19 patients), and the incidence of combined venous and arterial thrombotic events was 10%. CONCLUSIONS: There is considerable heterogeneity in the acute clinical management of patients presenting with rivaroxaban-related major bleeding. The use of PCC and dosage administered is inconsistent. TXA was utilised in only approximately one-quarter of all cases. Evidence-based guidance for treating rivaroxaban-related bleeding would improve the management of these patients and potentially improve clinical outcomes.

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.

Bing-Neel syndrome presenting as isolated CNS lymphoplasmacytic lymphoma: A case report and review of the literature.

Bing-Neel syndrome (BNS) is characterised by infiltration of the central nervous system by lymphoplasmacytic lymphoma (LPL) cells and is traditionally regarded as a complication of pre-existing systemic Waldenström's macroglobulinaemia (WM). We describe the case of a 49 year old woman with leptomeningeal LPL who did not fulfil diagnostic criteria for concomitant systemic WM at presentation, and who failed to respond to conventional chemotherapy treatment (including high dose methotrexate) but did respond to the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib. This highlights an important variation in the typical natural history of this rare disease and also further supplements emerging evidence regarding efficacy of ibrutinib in its treatment.

Informed consent for whole blood donation.

BACKGROUND AND OBJECTIVES: It is recognized that blood transfusion services have an ethical duty to obtain informed consent from their voluntary, non-remunerated donors. This right was most recently affirmed by the 2017 revision of the International Society of Blood Transfusion (ISBT) Code of Ethics. However, the constituent elements necessary to adequately inform such consent have not been definitively established. MATERIALS AND METHODS: This review evaluates the historical background to informed consent in medicine and as it has been applied to blood donation. The question of what information should be disclosed is then considered with regard to existing statutory requirements in both the United States and EU as well guidance from relevant international organizations. The emerging ethical issues around repurposing of donated blood for sale as recovered plasma and use in research are included in this analysis. RESULTS: A reasonable basis is found in the literature to advocate that valid informed consent of blood donors should encompass: the donation process itself and potential adverse effects, the need for pre-donation transfusion-transmissible infection (TTI) screening, potential non-transfusion uses of derived products, requirements to obtain and store personal information, the consequences that non-disclosure of such information may have for both the donor and the recipient and reassurance as to the confidentiality of this information. CONCLUSION: Informed consent is a key component of the duty of care between a blood service and its donor. We identify essential elements that should be present for such consent to be considered valid.

Feasibility of myelosuppressive chemotherapy in psychiatric patients on clozapine: A systematic review of the literature.

OBJECTIVE: Clozapine is the favoured antipsychotic for treatment-refractory schizophrenia, but has a 1%-2% incidence of agranulocytosis. Patients who require chemotherapy therefore pose a unique management dilemma for haematologists, oncologists and psychiatrists. METHODS: The Ovid MEDLINE and EMBASE databases were searched to identify reports describing use of clozapine concurrent with chemotherapy until 31 March 2019. The following terms (with variations) were used: neoplasm, cancer, tumour, malignancy, chemotherapy, antineoplastic and clozapine. RESULTS: Twenty-seven cases were included after reviewing titles and abstracts for relevance. Fifteen patients had solid organ tumours, and 12 had haematological malignancies, including three who underwent autologous haematopoietic stem cell transplantation (AutoHSCT). Clozapine was continued in 14 cases (albeit dose reduced in 2), with a reported median neutropaenic nadir of 0.29 × 109 /L (range 2.2 to <0.0 × 109 /L). Clozapine was discontinued or substituted for another antipsychotic in the remaining 13 cases, all except one of whom experienced marked psychiatric deterioration. The only neutropenia-related complication was one case of bacteraemia with high-dose melphalan conditioning for AutoHSCT. CONCLUSIONS: These findings argue in favour of clozapine continuation during chemotherapy. Further research is needed to develop guidance to minimise the risk of neutropenia-related complications from concurrent treatment.

Primary idiopathic CNS non-amyloidogenic light chain deposition disease complicated by treatment-resistant focal seizure disorder.

Light chain deposition disease (LCDD) is a systemic disorder characterised by the pathologic deposition of immunoglobulin light chains, which is histologically distinguished from amyloidosis by failure to stain with Congo red. Central nervous system (CNS)-restricted LCDD is among the rarest manifestations. We describe a unique case complicated by focal onset epilepsy with impaired awareness for which control with anticonvulsant therapy proved difficult.

Predictors of medical student remediation and their underlying causes: early lessons from a curriculum change in the University of Auckland Medical Programme.

AIMS: The purpose of this study was to identify predictors of remediation in a medical programme and assess the underlying causes and the quality of remediation provided within the context of a recent curriculum change. METHODS: A mixed methods study incorporating a retrospective cohort analysis of demographic predictors of remediation during 2013 and 2014, combined with thematic qualitative analysis of educator perspectives derived by interview on factors underlying remediation and the quality of that currently provided by the faculty. RESULTS: 17.7% of all students required some form of remedial assistance and 93% of all students offered remediation passed their year of study. Multivariate analysis showed international students (OR 4.59 95% CI 2.62-7.98) and students admitted via the Maori and Pacific Admission Scheme (OR 3.43 2.29-5.15) were significantly more likely to require remediation. Male students were also slightly more likely than their female classmates to require assistance. No effect was observed for rural origin students, completion of a prior degree or completion of clinical placement in a peripheral hospital. Knowledge application and information synthesis were the most frequently identified underlying problems. Most faculty believed remediation was successful, however, flexibility in the programme structure, improved diagnostics and improved access to dedicated teaching staff were cited as areas for improvement. CONCLUSIONS: Remediation is required by nearly a fifth of University of Auckland medical students, with MAPAS and international students being particularly vulnerable groups. Remediation is largely successful, however, interventions addressing reasoning and knowledge application may improve its effectiveness.

Macular thickness predictive of visual field sensitivity in ischaemic optic neuropathy.

PURPOSE: To investigate the ability of optical coherence tomography (OCT) parameters of macular thickness (MT) and peripapillary retinal nerve fibre layer (RNFL) thickness to differentiate eyes with nonarteritic anterior ischaemic optic neuropathy (NAION) from uninvolved eyes and to identify the relationship between macular and RNFL parameters and visual field sensitivity (VFS). METHODS: Thirty patients with unilateral NAION participated in a prospective observational cross-sectional study. Patients underwent Humphrey visual field (SITA Standard 24-2, HVF) testing and OCT to measure MT and RNFL. The contralateral uninvolved eye was used as controls. Areas under the receiver operating characteristic curves (AUROCs) of MT and RNFL for discriminating NAION from control eyes were also determined. The prespecified outcome measure was the correlation between RNFL, MT and mean deviation (MD). RESULTS: Average RNFL and MT were thinner in NAION eyes: 72.8 µm versus 98.9 µm (p<0.0001) and 231.9 µm (SD, 21.4) vs. 251.1 µm (SD, 14.8; p=0.0001), respectively. The largest AUROCs were for average MT (0.87) and average RNFL thickness (0.88). Overall, macular parameters showed stronger correlation with VFS than RNFL parameters. The highest correlation was average MT (0.71; p<0.0001) followed by RNFL parameter nasal quadrant RNFL (0.40; p=0.030). CONCLUSION: Both MT and RNFL show strong correlations with level of VFS in NAION. Macular thickness showed more robust correlations with VF and provides strong surrogate marker of the level of damage in NAION.

Optic nerve atrophy in adrenoleukodystrophy detectable by optic coherence tomography.

The adrenoleukodystrophies (ALDs) are a group of metabolic disorders characterised by the accumulation of very long-chain fatty acids in all tissues. The two most frequent ALD phenotypes are adult-onset adrenomyeloneuropathy (AMN) and childhood cerebral ALD. Visual system involvement in the adult phenotype is well described as impairment of visual function and optic disc pallor on clinical examination accompanied by demyelination of the optic nerves seen on MRI. Thinning of the retinal nerve fiber layer and ganglion cell death has been described in a neonatal form of ALD. Our patient provides evidence, through ocular coherence tomography scanning of the retina, that such degenerative changes also underlie the visual dysfunction seen in the AMN phenotype.