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.

Idarucizumab for the treatment of dabigatran-related nephropathy.

Anticoagulant-related nephropathy (ARN) is a clinical syndrome of acute kidney injury in patients taking vitamin K antagonists or direct oral anticoagulants. It is associated with increased mortality and there is no specific treatment. We report the case of a 78-year-old man on dabigatran who developed macroscopic haematuria and acute kidney injury 2 weeks after mitral valve repair, reaching a peak creatinine of 415 µmol/L from a normal baseline, which was successfully treated with one course of idarucizumab. This case illustrates the efficacy of an anticoagulant reversal agent for the treatment of ARN.

Treatment outcomes of patients with acute promyelocytic leukaemia between 2000 and 2017, a retrospective, single centre experience.

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are effective induction therapy for acute promyelocytic leukaemia (APL). However, early thrombo-haemorrhagic complications and mortality remain high. We aimed to investigate how the timing of ATRA initiation and the inclusion of ATO influence patient outcomes. Clinical records were retrospectively reviewed for all patients treated for APL in a single, tertiary centre during 2000-2017. Among 70 patients with APL, 36 (51.4%) presented with thrombo-haemorrhagic complications, and four (5.8%) died within 30 days. The median time to ATRA initiation was 11.2 (range 0-104) h from the time of admission. Patients requiring more transfusions started on ATRA sooner (P = 0.04). Patients with adverse early events did not start ATRA later (P = 0.99). Nevertheless, patients that required additional tests for diagnosis (PML immunofluorescence or molecular) started on ATRA later (28.5 versus 5.3 h; P < 0.0001), and had more thrombo-haemorrhagic complications (P = 0.04). Long-term survival was actually better in patients who started ATRA later (P = 0.03), which is likely explained by higher proportion of low risk patients in this group. Patients treated with ATO (n = 23) maintained higher fibrinogen levels and required less transfusions during induction (P < 0.05), with no disease-related deaths in this group over a median follow-up time of 37.8 months (interquartile range 44.9 months). In summary, fast ATRA initiation reduces early but not late adverse events in APL patients, and the inclusion of ATO helps further improve both early and late outcomes in APL.

Early treatment of acute promyelocytic leukaemia is accurately guided by the PML protein localisation pattern: real-life experience from a tertiary New Zealand centre.

Current guidelines recommend that a rapid test be used to assist diagnosis of acute promyelocytic leukaemia (APL), but the choice of an assay is discretionary. PML immunofluorescence (PML IF) identifies the microparticulate pattern of the PML protein localisation, highly specific for APL. The aim of this study was to evaluate clinical utility of PML IF in a real-life setting based on a retrospective records review for all patients who had PML IF performed in our centre between 2000 and 2017. Final analysis included 151 patients, 70 of whom had APL. PML IF was reported on average 3 days faster than cytogenetics. Compared with genetic results, PML IF showed sensitivity of 96% and specificity of 100%. PML IF accurately predicted APL in four APL cases with cryptic karyotype/FISH and excluded APL in 98% cases tested based on the suspicious immunophenotype alone, 21/28 of whom had mutated NPM1. Results of PML IF influenced decision to start ATRA in 25 (36%) APL patients and led to its termination in six non-APL patients. In conclusion, PML IF is a fast and reliable test that facilitates accurate treatment decisions when APL is suspected. This performance of PML IF remains hard to match in a real-life setting.

FISH detection of PML-RARA fusion in ins(15;17) acute promyelocytic leukaemia depends on probe size.

The diagnosis of acute promyelocytic leukaemia (APL) is usually confirmed by cytogenetics showing the characteristic t(15;17), but a minority of patients have a masked PML/RARA fusion. We report ten patients with APL and no evidence of the t(15;17), in whom the insertion of RARA into PML could not be demonstrated by initial FISH studies using a standard dual fusion probe but was readily identified using smaller probes. Given the need for rapid diagnosis of APL, it is important to be aware of the false negative rate for large PML/RARA FISH probes in the setting of masked rearrangements.