Leading the way for World Sickle Cell Day 2023

For World Sickle Cell Day 2023, we look at some of the ways that King's Health Partners Haematology is bringing together clinical, research and educational expertise to deliver world-class sickle cell care.   

What is Sickle Cell Disease? 

Sickle cell disease (SCD) is one of the most common serious inherited disorders. Affected individuals have red blood cells which become sickle shaped under certain conditions including low oxygen levels, dehydration, infection, and exposure to cold weather and stress.  

The sickle shape is rigid and unable to pass through small blood vessels easily, resulting in blockage and potential damage to organs. SCD can be complicated by episodes of severe pain requiring hospital admission (‘crisis’), chronic pain, stroke, increased risk of infection, impairment of brain, kidney, liver, spleen and respiratory function, and severe tiredness.  

Despite advances in recent years, SCD is still associated with reduced life expectancy. Quality of life for many with SCD is affected by chronic pain, low self-esteem, and negative impacts on relationships, education, and employment opportunities. 

Approximately 15,000 people with SCD live in the UK, and a large proportion of this population resides within south east London. Guy’s and St Thomas’ and King’s College Hospital NHS Foundation Trusts (NHS FTs) treat one third of the UK’s patients, leading on SCD treatment in many areas. We at King’s Health Partners Haematology are committed to working with patients and carers to help us shape our vision. 

Developing a Sickle Cell Centre of Excellence 

In collaboration with key partners, we're establishing a Centre of Excellence that goes beyond current commissioning capabilities. Our vision is to bring together world leading expertise in research, clinical delivery, and education, with the patient at the centre of this programme.  

The Centre of Excellence will bring together scientists from King’s College London with clinicians and patients from Guy’s and St Thomas’ and King’s College Hospital NHS FTs.  

Through this work, we wish to establish a leading research group through developing translational research projects with clinicians and patients, seeking funding for innovative early phase trials, and undertaking science-driven drug discoveries.  

Our clinical service vision encompasses mind and body elements, care closer to home, patient-led pathways delivery, streamlining multi-speciality clinical input, and supporting a sickle board in our Trusts that would have direct operational oversight on clinical delivery.  

Our education vision aims to reduce the significant shortfall in SCD clinical training for doctors and nurses. We hope to ensure that our future workforce is adequately trained for excellence in SCD. Through fellowship programmes we wish to train clinicians and scientists from the UK and abroad in all aspects of SCD care and research. Our ongoing training programme in the form of preceptorships are already delivering critical training to clinicians and raising vital funds for future project delivery.  

Responding to the APPG report 

The All Party Parliamentary Group on Sickle Cell and Thalassaemia (APPG) was founded in December 2008. The group has campaigned on multiple issues - including patient experience, prescription charges, and workforce - to keep Sickle Cell and Thalassaemia at the top of the political agenda. 

The APPG’s ‘No One’s Listening’ report examined the level of care patients with SCD receive when accessing secondary care, and determined actions required to improve care. The APPG reported national issues of sub-standard care, failings in providing joined-up care, low awareness among healthcare professionals, inadequate training, negative attitudes towards sickle cell patients and inadequate investment. It made 31 recommendations, seven of which were applicable to all NHS Trusts.  

King’s Health Partners welcomed the APPG report. Prior to the APPG report, we had established discussion of all mortality cases both departmentally and in a network multidisciplinary meeting, to ensure any learning or changes to processes could be systematically achieved. There was already a monthly network morbidity meeting, in addition to the local weekly meetings, to discuss complex cases and allow colleagues to seek timely specialist opinions and ensure equity of care throughout the network. At King’s College Hospital NHS FT, we have developed a live report of all our currently admitted cohort, accessible 24/7, to promote liaison and facilitate urgent review, even before patients are formally referred. 

We are working towards the recommendation to provide adequate analgesia within 30 minutes of presentation to all those presenting with pain due to SCD.  

We have fostered closer links with our ED colleagues and deliver regular teaching. There is clear signage at the ED entrance to ensure those presenting with SCD are prioritised for treatment due to the elevated risk of fast medical deterioration. We have developed an e-learning module for the management of acute pain and co-developed a film of patients and staff discussing their experiences. We have a designated sickle ward with enhanced training for nurses. We also ensure that there is an individualised care plan for each sickle cell patient, developed with the patient and published on their Electronic Patient Record to enable easy emergency access. 

We perform regular audits including a detailed patient survey to monitor user experience. There is a monthly adult patient support group, monthly virtual support group for parents of children with sickle disorders, updated patient information available in leaflet form and online. Proposed service developments are reviewed by patient representatives and user input informs the final design.  

The APPG report has acted as a catalyst to enable significant service improvement and further embed good practice and we are grateful to the group for highlighting these issues. 

Education

Education underpins excellent care. In the past 12 months we have organised many educational events across the breadth of health care professionals, including targeted training held at St Thomas’ Hospital for nurses and allied professionals. There is bitesized teaching for the emergency department and longer sessions aimed at different grades of medical trainees including specialist trainees. We organised and ran a highly successful preceptorship in September 2022, from which we earned enough to appoint a clinical fellow to support our work in SCD education. 

We have also generated an acute care training tool for healthcare professionals who manage the care of inpatients with SCD which is being implemented across Guy’s and St Thomas’ NHS FT. As part of this work, we have co-produced well-received educational videos with our patients.  

In conjunction with the Sickle Cell Society and Boston Scientific, a pharmaceutical company, we have also completed an educational animation tool on priapism, a common complication of SCD in men and boys. This is a complication which can have devastating outcomes, but which patients are very poorly informed of. The accessible tool which will be hosted online, ensuring wide reach aims to reduce the stigma and increase awareness in patients and carers. 

Research 

After many decades of slow progress, there are several exciting sickle trials actively recruiting across KHP, including trials of novel treatment agents, stem cell transplantation, and a large database study. Below are some details of three of these studies. 

An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-centre Study of Oral Etavopivat, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease 

Etavopivat (FT-4202) is a potent, selective, orally bioavailable, small-molecule activator of pyruvate kinase. This study is a randomized, placebo-controlled, double-blind, multicentre phase 2/3 study of patients, aged 12 to 65 years, with SCD. The clinical hypothesis is that pyruvate kinase activation will reduce the rate of sickle cell polymerization and improve red blood cell membrane function, reducing red blood cell (RBC) sickling and RBC haemolysis that led to vascular obstruction and anaemia, two hallmarks of SCD pathology. The trial objectives are to assess the efficacy of etavopivat in adolescents and adults with SCD as compared to placebo as measured by improvement in haemoglobin and annualized vaso-occlusive crisis rate. The recruitment target for this study has been reached. 

REDRESS study of haploidentical stem cell transplants in sickle cell disorders. 

This new study was launched in May 2023 to assess the effectiveness and feasibility of haploidentical stem cell transplants in sickle cell disorders SCD. Standard treatment for SCD is limited, with regular blood transfusions and hydroxycarbamide medications being the two widely available treatment options. Stem cell transplant (SCT) is a procedure where healthy stem cells from a matched donor are given to a person with a blood disease with the aim of curing the disease. Researchers have developed transplant protocols showing that SCT can be carried out safely in adults with high cure rates when receiving SCT from a 100% matched sibling. However, less than 10% of patients have a fully matched donor so this option is not available to them.  

Patients can also receive SCT from relatives who are a 50% match, for example, from a sibling with whom they share one parent, or from a parent - this is called haploidentical SCT. There were concerns that haploidentical SCT would not work due to high rejection rates and an unacceptable risk of complications, however new protocols mean it is now possible for haploidentical SCT to be performed. This is a clinical trial of haploidentical SCT compared to standard care in order to assess whether haploidentical stem cell transplant is safe and clinically and cost effective, with patients being randomised 1:1 to either receiving a haploidentical SCT or standard care.  

More information can be found on the website - Redress trial 

Natural History and Clinical Outcomes of Patients with Sickle Cell Disease: A Collaborative Multi-centre Database Study 

This is a non-commercial trial with the aim of setting up a research database to establish a cohort of adults with SCD to follow up prospectively to establish detailed natural history data to document patient outcomes and look for predictors of poor outcome to enable better understanding of which patients would benefit from earlier interventions, including stem cell transplantation and gene therapy. This prospective study does not propose that additional tests will be performed, but data from the investigations performed as part of the annual review will be collected from the electronic patient record along with an annual quality of life questionnaire. Over 430 patients have been recruited so far. 

King’s Health Partners Haematology brings together our strengths in clinical service, research, and education to deliver exceptional outcomes for haematology patients .