Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs. METHODS: We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner. RESULTS: The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk. CONCLUSION: The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML.

Bleeding related hospitalizations and mortality in England 2014-2019.

Acute bleeding is common and associated with increased morbidity and mortality. Epidemiological studies evaluating trends in bleeding-related hospitalisations and mortality are important as they have potential to guide resource allocation and service provision, however, despite this literature evaluating the national burden and annual trends are lacking. Our objective was to report the national burden and incidence of bleeding-related hospitalisation and mortality.This was a population-based review of all people in England between 2014 and 2019 either admitted to an acute care ward of a National Health Service (NHS) English hospital, or who died. Admissions and deaths were required to have a primary diagnosis of significant bleeding.There was a total of 3,238,427 hospitalisations with a mean of 539,738 ± 6033 per year and 81,264 deaths with a mean of 13,544 ± 331 per year attributable to bleeding. The mean annual incident rate for bleeding-related hospitalisations was 975 per 100,000 patient years and for mortality was 24.45. Over the study period there was a significant 8.2% reduction in bleeding related deaths (χ2 test for trend 91.4, p < 0.001). A direct relationship between increasing age and incidence of bleeding-related hospitalisation and mortality was seen.Bleeding remains a common cause of hospitalisation and death. The reduction in bleeding related mortality requires further investigation. This data may serve to guide future interventions designed to reduce bleeding-related morbidity and mortality.

UK prescribing practice of anticoagulants in patients with chronic kidney disease: a nephrology and haematology-based survey.

A survey to gain insight into anticoagulant prescribing practice in the setting of chronic kidney disease (CKD) across the UK was disseminated via renal and haematology networks. Areas of anticoagulant use included patients with venous thromboembolism (VTE), requiring thromboprophylaxis for VTE, Atrial Fibrillation (AF) and nephrotic syndrome.An online-survey was disseminated via British Haematology Society, UK Kidney Association, and Renal Pharmacy Group over a five month period. All responses were voluntary and anonymous.Among 117 responses there were 49 nephrology doctors, 47 renal pharmacists and 20 haematology clinicians. A specialist multidisciplinary team to discuss the specific anticoagulant management of these patients was only available to 3% (4/117) respondents. Renal function estimate used for anticoagulant dosing was mainly Cockcroft-Gault for pharmacists and haematology but lab-based estimates were used by nephrology doctors. Therapeutic dose of Low Molecular Weight Heparin was mostly likely to be reduced by one-third when used for VTE treatment, with the majority of units undertaking anti-Xa monitoring in CKD stage 5 and dialysis. Direct-acting Oral Anticoagulants are being used in patients with nephrotic syndrome, those with CKD stage 5 and on dialysis for VTE and AF in the absence of license in these indications.This survey highlighted the significant differences between anticoagulant prescribing in CKD between two professional specialties and marked variation between centres in anticoagulant management strategies employed for these patients. With gaps still existing in the evidence base and answers to these not expected within the next few years, development of a best-practice guideline would be warranted to support clinicians in this field.

A Novel Risk Prediction Score for Clinically Significant Bleeding in Patients Anticoagulated for Venous Thromboembolism with Active Cancer.

BACKGROUND: Cancer-associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction. METHODS: UK Clinical Practice Research Datalink data (2008-2020) were used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding and clinically relevant nonmajor bleeding requiring hospitalization (CRNMB-H). A scoring scheme was developed from sub-distribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation. RESULTS: A total of 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds, and 376 CRNMB-H were identified after adjudicated review in 4,914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding included cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract, metastases, minor surgery, minor trauma, and history of major bleeding or CRNMB (before or after the Ca-VTE diagnosis). Patients recognized as low, medium, and high risk (30.4, 56.8, and 1.7% of the population, respectively) had a 6-month significant bleeding incidence rate of 5.1, 19.0, and 56.5 per 100 person-years, respectively. Overall C-statistic for significant bleeding was 0.70 (95% confidence interval: 0.65-0.75), and 0.76 (0.68-0.84) and 0.67 (0.61-0.73) for major bleeding and for CRNMB-H, respectively. CONCLUSION: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

Assessment of current clinical practice throughout the UK for the diagnosis and management of monoclonal gammopathy of renal significance.

Since the inception of the term monoclonal gammopathy of renal significance (MGRS) in 2012 by the International Kidney and Monoclonal Gammopathy Research Group, there have been no consensus guidelines specifically pertaining to the UK regarding to patient management. We aimed to identify both regional and cross-discipline variation in current clinical practice, to provide insight and rationale for a potential standardised pathway in the future. A national survey of 88 consultants from the disciplines of haematology and nephrology was conducted between June 2020 and July 2021. Agreement was evident for aspects of the diagnostic pathway, including presenting features likely to raise suspicion of MGRS and the most pertinent confounding factors to consider before renal biopsy. However, significant variability was identified in both the cohort of diagnostic tests used, as well as urinary work-up for patients with suspected MGRS. Treatment and monitoring frequency was also an aspect of management identified as variable. Despite differences in clinical practice across the UK, MGRS diagnosis was widely regarded to be the joint responsibility of both disciplines. The results provide an indication of inter-regional and interdisciplinary differences in practice, highlighting the need for improved awareness and standardised protocol for management of MGRS that applies to the UK population.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

OBJECTIVE: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. METHODS: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. RESULTS: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. CONCLUSION: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis. METHODS: We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included. RESULTS: Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile. CONCLUSION: Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.