Search

Anaemia is a condition commonly encountered in many clinical specialities, including chronic heart disease, haemato-oncology, gastroenterology, gynaecology/obstetrics, renal disease and care of the elderly. In recent years, anaemia has emerged as a significant public health issue due to the appreciation that it has profound implications as a comorbid factor for other illnesses, while in itself presenting a serious health risk factor. This article explores the definition, classification and current treatment options for anaemia. It describes the move within a central London acute trust to a nurse-led service and the favourable patient satisfaction results that have emerged from an initial survey.

Intravenous iron therapy is a useful treatment for the rapid correction of iron deficiency anaemia and can be used to avoid or reduce the requirement for allogeneic blood transfusion. Several intravenous iron preparations are available commercially which differ in cost, mode of administration and side effect profile. There are few data directly comparing the efficacy of these preparations. In this retrospective single-centre study, we present the results from two hundred and eight patients treated using three different iron preparations (iron dextran, iron sucrose and ferric carboxymaltose) and compare the effect on haemoglobin levels and other measures of iron deficiency six weeks after treatment. Within the limitations of our study design, we show a statistically and clinically significant difference in efficacy between these preparations.

Deepti Radia,1 Ibrahim Momoh,2 Richard Dillon,1 Yvonne Francis,1 Laura Cameron,1 Toni-Lee Fagg,1 Hannah Overland,1 Susan Robinson,1 Claire N Harrison11Haematology Department, Guy's and St Thomas' NHS Foundation Trust, London, UK; 2Bupa Home Healthcare, Harlow, UKAbstract: This article describes the initiation and evolution of the Rapid-Access Anemia Clinic (RAAC) at Guy's and St Thomas' Hospitals, London, UK. This clinic was set up to provide diagnosis and treatment, and to coordinate investigative procedures, where necessary, into the underlying causes of anemia. Initially piloted with anemic preoperative orthopedic patients, the clinic now treats a wide range of conditions, deriving from both internal and external referrals. Treatment includes dietary advice, supplementation with iron, vitamin B12 and folate, and blood transfusion. Most patients at the RAAC need iron replacement, the majority of which require intravenous (IV) iron. Therefore the first-line IV iron-administration protocol is carefully considered to ensure viability of the service and patient satisfaction. Four IV irons available in the UK are discussed, with explanation of the benefits and drawbacks of each product and the reasoning behind the IV iron choice at different stages of the RAAC's development. Costs to the service, affected by IV iron price and administration regimen, are considered, as well as the product's contraindications. Finally, the authors reflect on the success of the RAAC and how it has improved patients' quality-of-treatment experience, in addition to benefiting the hospital and National Health Service in achieving specific health-care mandates and directives. Drawing from the authors' experiences, recommendations are given to assist others in setting up and providing a successful rapid-access anemia service or similar facility.Keywords: hemoglobin, iron deficiency, ferric carboxymaltose, iron sucrose, iron dextran, iron isomaltosideA Letter to the Editor has been received and published for this article.

Abstract 4368 Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired bone marrow disorder characterised by intravascular hemolysis with resultant anemia often leading to transfusion dependence, severe disabling symptoms and, frequently, life threatening thrombosis. Historically the management of PNH was largely supportive, relatively ineffective and resulted in frequent visits to hospital, admissions, an inability to function normally including loss of employment or other daily activities. PNH is a chronic condition and in most patients persists for the remainder of the patient’s life. Eculizumab was first used for PNH in 2002 and has been licensed since 2007. Eculizumab has been reported to improve all symptoms due to hemolysis in PNH as well as preventing the common complications, such as thrombosis and renal failure and normalising survival. However eculizumab has to be given as an intravenous infusion every 2 weeks indefinitely. In the UK PNH is managed in a shared care model between local hematologists and the National PNH Service from two Centres based in St James’s University Hospital, Leeds and Kings College Hospital, London. Here we report the management of patients treated with eculizumab within the PNH National Service. A total of 130 patients have been treated with eculizumab since May 2002 with 120 currently receiving therapy. 5 patients have died and none were directly related to PNH or eculizumab. 99 patients requiring transfusions prior to eculizumab have been on treatment for at least a year and 65 (66%) of these have not required transfusions for at least the last 12 months. The rarity of PNH means that patients frequently have to travel long distances for review and treatment. This leads to major issues both in terms of time commitment and expense. In order to allow patients to lead as normal lives as possible we have developed a service model in which Specialist PNH Clinics are performed regionally by the PNH Centre and in which patients receive eculizumab every 2 weeks in their homes delivered by a homecare nursing team. In the UK, the PNH Service and Healthcare at Home Ltd (www.hah.co.uk) have been working in partnership for over 7 years during the clinical trials of eculizumab and since its license in 2007. The PNH Service manages the prescription and delivery of eculizumab including an education program for the homecare nurses. This innovative home infusion programme ensures the safe administration of eculizumab outside of the hospital environment, leading to enhanced treatment-associated convenience for patients and their families. Each year the home infusion program has grown, now over 3000 infusions are given annually including whilst patients are on holiday, visiting family, at University or in the workplace. A recent patient survey has been conducted from the 2 PNH Centres to assess the patients’ experience of their PNH diagnosis and treatment. 122 patients responded with 70 of these patients receiving treatment with eculizumab and all currently on the home infusion programme. 63 of 68 patients reported the homecare service as excellent or very good compared to 1 reporting it as poor and 66 of the 68 patients preferred to have their treatment at home compared to hospital. The patients main concerns before starting treatment were reduced life expectancy and the requirement for blood transfusions along with fatigue. With eculizumab treatment and the convenience of homecare 30 patients reported being able to return to work. The homecare service is supported by contact between the clinic appointments, 56 of 67 patients having contact with their PNH Specialist Centre by phone or email in addition to the care of the patient’s local hematology team that over 90% of the patients continue to see. The impact of PNH on patients lives before eculizumab treatment was rated and improved from a median of 3 out of 10 (0 = no quality of life; 10 = normal) prior to eculizumab to a median of 8 out of 10 on treatment. In summary, a novel model of provision of care in PNH with Outreach Specialist Clinics, a 24 hour on call service and homecare delivery of eculizumab permits the normalisation of patients’ lives and overcomes most of the hurdles associated with prolonged regular intravenous therapy. This allows patients to benefit fully from eculizumab including reduction in transfusions, the prevention of serious complications, normalisation of quality of life and where appropriate a return to work. Disclosures: Arnold: Alexion Pharmaceuticals: Honoraria. Kelly:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Hill:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Richards:Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Elebute:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Hillmen:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract 4240 Background: PNH is an acquired haemolytic anaemia which is characterised by intravascular haemolysis. The disease is due to a somatic mutation of the PIG-A gene in haematopoietic stem cells resulting in loss (complete or partial) of glycosylphosphatidylinositol-(GPI) anchored proteins on the cell surface. The lack of CD59, one of the GPI-anchored proteins, on the red cell surface leads to increased susceptibility to complement-mediated intravascular haemolysis. Eculizumab is a monoclonal antibody that inhibits the complement protein C5 by preventing its cleavage and leads to transfusion independence in 50% of the patients. Objective: To determine the role of C3 –mediated opsonisation of PNH cells, as we found a significant number of patients treated with Eculizumab still needing transfusion. Results: Twenty six PNH patients treated with Eculizumab and 22 patients from an untreated non transfusion dependant PNH cohort were analysed. Transfusion dependency was present in 14 of 26 patients (54%) compared with transfusion independence in 12/26 (46%) patients. Direct anti-globulin test (DAT) was positive in 21 of 26(81%) patients during eculizumab treatment, while DAT was positive in 2 of 24 untreated patients (8%).All except one patient (20/21) with positive DAT had C3d positivity at varying levels. There was no correlation between the strength of C3d positivity and transfusion dependency. Of the 21 patients who had a positive DAT during eculizumab treatment, samples were available for 16 patients prior to treatment, and 7 of 16 were DAT positive. All the 7 patients were weakly positive for IgG and only one patient had C3d positivity at a low level. The two untreated patients were also only weakly positive for IgG. Among the eculizumab treated patients, 14 of the 21(67%) with a positive DAT test received at least two transfusions compared with no transfusions in the 5 DAT negative patients (p Conclusion: Eculizumab treatment in PNH patients has resulted in significant reductions in transfusions in a majority of patients, though some patients still require transfusion at a low intensity. The observation of C3 fragments on PNH red cells reveals an extravascular haemolytic pathway which is unmasked by Eculizumab treatment as evidenced by finding new DAT positive tests. The finding of positive DAT test in a 9 of 50(18%) untreated haemolytic PNH patients demonstrates the utility of flow cytometry to analyse PNH clones when clinical suspicion is high, as conventionally finding DAT positivity indicates autoimmune haemolytic process and excludes diagnosis of PNH. The true detection of C3d on red cells causing a positive DAT test post treatment, rather than due to allo-antibodies is important. There is a proportion of patients (33%) who became DAT positive but never needed transfusion indicating the contribution of other factors like bone marrow failure, intercurrent infections in the transfusion dependent DAT positive group. Eculizumab is effective in resolution of intravascular haemolysis, but unmasking of low level C3d mediated haemolysis is an important phenomenon which is not entirely responsible for the persistent transfusion requirement in a subset of patients. Disclosures: No relevant conflicts of interest to declare.