Oral iron chelation therapy with deferiprone (L1)

Aims: To evaluate the oral iron chelator deferiprone (L₁) by conducting 2 long-term clinical trials in patients with iron overload and to assess its effectiveness and study its adverse effects both in vivo and in vitro. Results: L₁ was used long term(>6 months) in 53 patients with iron overload at a dose of approximately 50-100mg/kg/day. Urinary iron excretion (UIE) ranged between 5.3 and 66.8mg/24h. In a significant number of patients a dose in excess of 60mg/kg/day was required to induce a UIE in excess of 0.5mg/kg/day to result in a negative iron balance. No significant change in the mean UTE was observed when L₁ was given with or without food or vitamin C or in 2 or 4 divided daily doses. Serum ferritin fell in 36 of the 53 patients (68%) treated long term. The fall in serum ferritin was more marked in those patients with the highest body iron load as assessed by serum ferritin levels. Two patients developed agranulocytosis and 3 less severe neutropenia whilst receiving L₁. Studies using liquid culture systems have failed to show an increased susceptibility of the patients' myeloid precursors (CFU-GM) to L₁, alone or bound to iron, compared to normal myeloid precursors. Furthermore, the toxicity of free or iron bound L₁ to normal or the patients' myeloid precursors was less than that of desferrioxamine (DFX). Joint or musculoskeletal problems was observed in 14 of 53 (26%) patients treated long term. The results here show for the first time that L₁ can cause mild zinc deficiency in some patients. This was more marked in patients with diabetes mellitus. Nine of 63 patients (14%) treated with L₁ developed nausea and 17 of 54 (32%) developed a transient fluctuation in the serum level of aspartate transaminase (AST). L₁ was rapidly absorbed (abt1/2: 22.2±17.7min) and eliminated (elt1/2: 9l.1±33.1min) mainly as L₁-glucuronide (L₁G) but also as free L₁ and L₁-iron complex in urine. L₁ efficiency was 3.8±1.9%. It was found that L₁G can accumulate in patients with impaired renal function. Using urea-polyacrylamide gel electrophoresis L₁ was found to be capable of removing significant proportion of transferrin iron. Assuming that all the iron removed from transferrin by L₁ was excreted in urine in 24 hours, it was found that this comprised 21.3±20.2% (5.8-67.1%) of total UIE. Using an HPLC (high-pressure liquid chromatography)-based method L₁ was found to be capable of causing a significant fall in the serum concentrations of non-transferrin-bound iron in patients with iron overload. Conclusions: L₁ was shown to be an effective iron chelator in inducing a significant urinary iron excretion in a considerable number of patients leading to a reduction in body iron stores as evident by a fall in serum ferritin. But long-term use was associated with adverse effects the most important of which were agranulocytosis and joint toxicity

A District General Hospital Experience of Patients Receiving Apixaban, Dabigatran, Rivaroxaban or Warfarin for Anticoagulation

Abstract Introduction Novel oral anticoagulants (NOACs) are becoming increasingly more prevalent as a preventative measure for venous thromboembolism and stroke prevention in atrial fibrillation (AF)1. NOACs are considered non inferior to Vitamin K antagonists (VKAs) in terms of efficacy and clinical trial evidence has suggested lower rates of complications with the use of NOACs2. There is limited published literature on the complication rates of NOAC use in the district general hospital setting. In this retrospective study, the bleeding rates amongst patients on oral anticoagulants in a district general hospital in the United Kingdom were established. Methods All patients prescribed a NOAC (Rivaroxaban, dabigatran or apixaban) or a VKA at the Princess Alexandra Hospital, a district general hospital in Harlow, United Kingdom, between 01/01/2015 and 31/12/2015 were identified from hospital pharmacy records. Electronic patient hospital records of these individuals were reviewed to identify indication for anticoagulation and any subsequent bleeding complications after initiating therapy as classified according to ICD-10 up until 31st of June 2016. Results A total of 521 patients were prescribed a NOAC. 283 patients were prescribed Rivaroxaban, 217 patients Apixaban and 21 patients were prescribed Dabigatran. 969 patients were prescribed a VKA. From 1st of January 2015 to June 31st 2016, 5.9% of NOAC patients suffered a bleed requiring a hospital visit during this time, versus 7.1% patients on a VKA. Amongst patients prescribed a NOAC, common causes of bleeding included GI haemorrhage (34.5%), epistaxis (38.0%), haemoptysis (13.8%). Amongst patients prescribed a VKA, common causes of bleeding included gastrointestinal bleeding (57.0%), epistaxis (25.2%), haemoptysis (11.9%). Rates of cerebral haemorrhage were low in both groups (0.77% of patients prescribed a NOAC and 0.61% of patients prescribed a VKA). Conclusion This data illustrates real-world experience of bleeding rates requiring hospital admission of patients on NOACs and VKA. The data suggests a lower bleeding complication rate amongst a district general hospital patient population taking NOAC compared to VKA, in keeping with previously published data. References 1. Beyer-Westendorf J, Förster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, Michalski F, Köhler C, Werth S, Sahin K, Tittl L. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood. 2014 Aug 7;124(6):955-62. 2. Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014 Oct 9;124(15):2450-8. Disclosures No relevant conflicts of interest to declare. </jats:sec

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479