In the context of rare disease, the specialist nurse is recognised as having an essential role in ensuring that patients receive an accurate and timely diagnosis coupled with appropriate treatment (Knight, 2011; Stanback, 2014). The role of ‘care co-ordinators’ in providing a positive care experience for patients with rare diseases, to reduce the sense of isolation often felt by this group, has been emphasised in recent reports (Morris et al, 2022; Genetic Alliance UK, 2023. Specialist nurses play a vital role in reducing the number of hospital stays for patients with rare diseases by recognising symptoms at an early stage, ensuring that patients adhere to therapy and by providing psychosocial support (Pati, 2010).
A review of the literature reveals that there has been little previous work to appraise the role of the specialist nurse caring for patients with thrombotic thrombocytopenic purpura (TTP). Harrison (2021) described the treatment of TTP patients in a single centre over the past 10 years. In that article, Harrison (2021) considered the role of the specialist nurse in caring for TTP patients and argued that one of the key roles is to raise awareness about the condition, and to educate and support other nurses to look after this patient group.
NHS England recently commissioned TTP services at nine designated regional specialist centres in England. The service specification requires that regional specialist centres must have a specialist nurse as part of the specialist multidisciplinary team (NHS England, 2022).
This article seeks to consider the current and future value of the specialist nurse in providing acute and long-term care to patients diagnosed with TTP. To fully appreciate the challenges and infrastructure of care required for this condition a summary of the disease and management is included.
Background
TTP: an overview and current management
TTP is a rare and life-threatening blood disorder characterised by low platelets, microangiopathic haemolytic anaemia and ischaemic organ damage resulting from microvascular thrombosis. It presents as a life-threatening medical emergency but, following a remission, also requires lifelong monitoring to avoid relapse and to support patients with long-term complications of the disease. Untreated, the mortality rate is more than 90% (Scully et al, 2008).
TTP is caused by a deficiency of the Von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). It has an incidence of between two and six patients per million per year (Zheng et al, 2020a). Clinical features of TTP may include bruising, headaches, blurred vision, confusion, seizures, fever and gastrointestinal upset. If left untreated, TTP can lead to multi-organ failure (Scully et al, 2008). Patients can present with multiple symptoms and signs, making the condition difficult to diagnose. Long-term complications for survivors include severe cognitive and neurological impairment, reduced kidney function, cardiac issues and long-lasting psychological problems, including anxiety, depression and post-traumatic stress disorder (Han et al, 2015; George, 2018; Holmes et al, 2021).
TTP can affect males and females of any age or ethnicity; however, it is more common in women, those aged between 30 and 50 years and those of Black ethnicity (Nuñez Zuno and Khaddour, 2023). Immune TTP (iTTP) is caused by the development of autoantibodies against ADAMTS13 and can be triggered by infection, pregnancy, surgery and medications (including hormone replacement therapy), and it can be associated with other autoimmune disorders such as systemic lupus erythematous (Kucukyurt and Eskazan, 2020). However, in most cases the trigger is unknown. In a small proportion of patients the deficiency of ADAMTS13 may be congenital and present in childhood, or may remain undetected until the individual experiences an acute episode, often during pregnancy.
First-line treatment for iTTP is a combination of plasma exchange (Padmanabhan et al, 2019), corticosteroids, the anti-CD20 monoclonal antibody rituximab and the monoclonal, bivalent humanised immunoglobulin fragment antibody caplacizumab (Zheng et al, 2020b). Treatment aims can be divided into two components. First, the aim is to achieve haematological remission whereby the patient's blood counts return to normal and the acute TTP episode is over. The second aim is to achieve an immunological remission where the ADAMTS13 levels return to normal. This prevents exacerbation and acute TTP relapse. Patients who do not achieve immunological remission with rituximab and steroids may require additional immune suppression (Ahmad et al, 2007; Eskazan, 2016; Rottenstreich et al, 2016; Scully et al, 2023).
Mortality is increased relative to age. Some 20–50% of patients diagnosed with TTP will experience a relapse after their initial diagnosis and a recurrence of TTP can happen at any time, even if a patient has been in remission for many years (Willis and Bandarenko, 2005).
Acute TTP: referral, early diagnosis and time to treatment
Suspected TTP should be treated as a medical emergency because there is a substantial risk of early death, which is preventable by prompt treatment. Early initiation of plasma exchange, ideally within 4–8 hours of suspected diagnosis, is essential in improving outcomes for patients with TTP and is the single greatest indicator of survival (Zheng et al, 2020b). Treatment can start when the diagnosis of TTP is suspected; however, confirmation of diagnosis requires demonstration of a low ADAMTS13 level.ADAMTS13 assays are available only in specialist laboratories and 24-hour access to plasma exchange is not available in many hospitals, necessitating prompt referral to a specialist TTP centre for treatment. Initial diagnosis of this patient group often takes place away from the specialist TTP treatment centre, therefore patients with a suspected TTP diagnosis require immediate transfer by category 2 ambulance to expedite their arrival at the specialist regional centre.
During an acute inpatient admission, TTP patients often require high levels of medical and nursing intervention within the intensive care unit (ICU) setting, up to and including intubation, mechanical ventilation and vasopressor support in the event of cardiovascular compromise, which is often associated with unsurvivable TTP (Azoulay et al, 2019; Dutt et al, 2021). Caring for TTP patients within the ICU ensures the close monitoring of a patient group at significant risk of sudden deterioration and facilitates more rapid insertion of central venous catheters, resulting in faster initiation of plasma exchange (Azoulay et al, 2019).
Early initiation of rituximab, corticosteroids and caplacizumab are also associated with improved patient outcomes and are recommended by the International Society of Thrombosis and Haemostasis and the British Society for Haematology as best practice in treating TTP (Zheng et al, 2020b; Scully et al, 2023). Rituximab works by targeting B cells to prevent the body from producing autoantibodies to ADAMTS13. Although it is not proven to reduce mortality, rituximab reduces the risk of relapse in patients who survive their initial episode of TTP by up to 85% (Jestin et al, 2018). Caplacizumab inhibits the interaction between vWF and platelets, thus preventing ultralarge vWF-mediated platelet adhesion and reducing the risk of microthrombi formation. Its introduction has significantly reduced the duration of plasma exchange and hospital stay for patients by reducing the length of time to platelet recovery (Scully et al, 2019; Völker et al, 2020; Coppo et al, 2021).
The role of the TTP specialist nurse
Referral and acute care of the TTP patient
Once TTP is suspected, the referring team must contact their nearest specialist centre urgently to arrange the referral and transfer of the patient. During daytime hours, the TTP specialist nurse acts as a co-ordinator in this process by contacting pharmacy, therapeutic apheresis services and the transfusion laboratory, mitigating any potential delays to plasma exchange and treatment.
Throughout the acute admission period, the TTP specialist nurse works as part of the clinical team to review patients daily. The specialist nurse plays a vital role in developing, implementing and evaluating a tailored treatment plan according to the patient's response. The TTP specialist nurse works closely with the ward team and specialist coagulation laboratory to ensure that blood tests including ADAMTS13 have been sent, and that care is appropriately commenced. The specialist nurse also liaises with the therapeutic apheresis and pharmacy teams to facilitate urgent or elective treatment as needed.
During acute diagnosis and treatment, the specialist nurse plays a vital role in patient advocacy. Due to the complexity of TTP at the point of first presentation, newly diagnosed patients can find decision-making and discussing their concerns challenging. Many patients feel more comfortable asking questions and sharing their fears with a familiar nurse (Schroeter, 2007). The TTP specialist nurse makes regular contact with patients during their inpatient stay to ensure that their needs are met and to empower them to ask questions about their condition and treatment.
Over time, the TTP specialist nurse works closely with patients and their families to provide teaching about the pathophysiology of TTP and associated treatments, thereby increasing their health literacy (Pereira et al, 2020) and creating an ‘expert patient’ who can take an active role in maintaining their own health and making decisions about their care (Tattersall, 2002; Cordier, 2014; Boulet, 2016). The role of the TTP specialist nurse has been acknowledged as critical to ensuring effective interaction between the multiple clinical teams involved in the care of the TTP patient and in supporting patient advocacy (Dutt and Scully, 2015).
When patients are due to be discharged from hospital following their initial presentation, the TTP specialist nurse provides information and support regarding the emotional implications of receiving a TTP diagnosis, on returning to work, signs and symptoms of relapse, and also contact details for patients to access advice 24/7. This is the beginning of a long-term relationship between the patient and the TTP nurse, which enables the patient to return as far as possible to their pre-diagnosis quality of life.
Patients recovering from TTP can experience significant issues with memory, cognitive functioning and low mood (Falter et al, 2021). Building a strong rapport at an early stage in their diagnosis enables patients to discuss these issues openly with the TTP specialist nurse. Shaw et al (2023) considered the experience of a specialist centre in integrating psychology services for patients with TTP and highlighted the ‘bridge’ between the patient and psychologist provided by the TTP specialist nurse and consultant. NHS England's highly specialist commissioning includes psychology provision at TTP specialist centres and the TTP specialist nurse can signpost patients to the designated TTP psychologist by explaining how the service works and what support can be provided. This may include support with understanding and accepting their diagnosis, and regaining quality of life through developing coping strategies in relation to the emerging neurocognitiv difficulties.
Long-term care of the TTP patient
Once patients have been discharged from hospital the TTP specialist nurse acts as a point of contact for patient queries and concerns. The nurse also plays a key role in providing ongoing education and support to patients and their families regarding their condition and early recognition of signs and symptoms of relapse (Pereira et al, 2020). Patient survey feedback from the TTP specialist service in Liverpool in 2021 revealed that patients view their specialist nurse as a valuable resource. They stated that the TTP specialist nurse would be their first point of contact should they have any questions or concerns regarding their disease, and said that their specialist nurse gave them more confidence in managing their condition. Patients felt that their TTP specialist nurse had a unique understanding of their needs based on an in-depth knowledge of the condition, which led to the provision of personalised care.
The TTP specialist nurse supports the delivery of outpatient clinics to ensure that patients are regularly monitored, as appropriate, and receive prompt treatment in the event of a suspected relapse. NHS England-commissioned recommendations currently suggest that patients with TTP should be followed up weekly in the first month following discharge, every 2–4 weeks for the following 3 months, 3 monthly for 12 months, and then 3–6 monthly thereafter. During clinic appointments, patients undergo vital signs monitoring, blood tests including ADAMTS13, full blood count, lactate dehydrogenase (LDH), and liver and kidney function to identify any potential decline in haematological markers, and an assessment of signs and symptoms of TTP that may suggest patients may be at risk of relapse.
Patients whose ADAMTS13 levels have dipped may be considered for treatment with rituximab therapy to prevent acute relapse (Zheng et al, 2020b). For these patients, the TTP specialist nurse co-ordinates treatment within the outpatient setting through liaison with the medical day ward and pharmacy department. The specialist nurse also ensures patient safety through facilitation of the informed consent process and pre-treatment safety checks, including verification of hepatitis B status. This helps to avoid reactivation of any previous hepatitis B virus, which may be fatal in patients receiving immunosuppressive therapy. Treating patients prophylactically in advance of haematological relapse indicators, such as thrombocytopenia and microangiopathic haemolytic anaemia, reduces the need for prolonged hospital admission and interventions, such as plasma exchange, and lessens the likelihood of long-term end organ damage caused by acute episodes of TTP (Jestin et al, 2018). Acute relapse in TTP would require admission to intensive care and treatment, as if it were the first presentation of the disease, with consequent significant cost and mortality implications.
Pregnancy and TTP
TTP can present for the first time during pregnancy, usually within the third trimester or in the post-partum period. With this comes an increased risk of maternal and fetal mortality. Subsequent pregnancies may present a risk of relapse. A well-documented treatment plan is required, as well as a multidisciplinary approach, including liaison with haematology obstetric services, which are critical to improving maternal and fetal outcomes (Scully, 2021). Close, regular monitoring of these complex patients is essential and the TTP specialist nurse must liaise with all members of the multidisciplinary team to ensure that they are aware of the process to be followed to achieve a successful outcome for both mother and baby.
Patient Information and engagement
Provision of both verbal and written patient information is highly important for patients with TTP and it empowers them throughout their disease (Harrison, 2021). Patient information leaflets offer a resource for patients who may have neurocognitive issues, providing answers to many of their questions and easing their concerns. Information leaflets designed and distributed by the TTP specialist nurse include general TTP patient information about the condition and treatments, ‘going home after admission’ discharge advice for patients with TTP, contact details for the specialist TTP team, and patient alert cards. The patient alert card is particularly valuable as patients can show this to health professionals in the event of a hospital admission. The card provides details of the patient's diagnosis and contact details for their specialist TTP team for advice both in and out of hours.
Patient support groups are an essential resource for patients living with rare diseases such as TTP (Delisle et al, 2017). For patients presenting with rare diseases, there are often far smaller support networks than for those diagnosed with widely recognised and researched conditions such as diabetes. This can lead to patients feeling isolated, or that there is nobody they can talk to who will understand their experience. Participation in patient support groups enables individuals to share their experiences of living with TTP, to learn more about their disease, and to give and receive emotional support, which in turn leads to patient empowerment and opportunities for patients to advocate to improve TTP services (Delisle et al, 2017). Within the Northwest of England, there is an active network of patients involved with the local TTP Patient Support Group within which the TTP specialist nurse plays an important role in organising and facilitating patient meetings to discuss issues, including updates on available treatments and services, research studies and topical issues such as COVID-19 vaccination.
National patient groups, including the TTPNetwork (https://www.ttpnetwork.org.uk), also play a vital role in achieving this aim and the TTP specialist nurse may signpost patients and their families to support services offered by the group. The TTP Network is a registered charity that supports patients, their families, friends and medical staff. It provides information and sources of help for TTP, including documents to help when travelling abroad, links to best practice guidelines and the opportunity to make contact with others dealing with TTP.
The involvement of the TTP specialist nurse in patient engagement activities assists in the creation of services aligned to patient needs and can help improve the health of patients by offering them the opportunity to engage with their peers and the TTP service, and to have their ideas heard (Healthcare Quality Improvement Partnership, 2017). Previous patient engagement activities have resulted in the production of a TTP information leaflet for health professionals designed by a patient in partnership with the TTPNetwork. Facilitating patient involvement events, including support groups and gathering regular patient feedback as part of a patient survey programme, enables the TTP specialist nurse to ensure that the service is responsive to patient needs and expectations (Vahdat et al, 2014), offering patients the opportunity to feel like their input is making a difference to the care they receive.
Psychological support
TTP specialist nurses play an important role in the long-term emotional and psychological support of patients and their families. TTP patients exist at a difficult point of intersection between chronic disease, acquired brain injury and post-traumatic stress arising from sudden ICU admission. Adjusting to an ‘un-well’ identity and the need to undertake a constant process of self-monitoring for signs of relapse can easily lead to anger, low mood and anxiety, and can be highly triggering of previous traumatic treatment experiences. These factors can in turn produce relational distress in family networks if appropriate support is not provided.
The introduction of psychology services within the TTP care pathway is still in the early stages, as described by Shaw et al (2023). Through referral to specialist psychology services, the TTP specialist nurse can ensure that patients and their families receive the appropriate support they need to understand what has happened and to move forward past the diagnosis, enabling the patient to regain a good quality of life. Psychology services also play an important role in identifying and developing coping strategies in relation to the emerging neurocognitive difficulties faced by patients following their TTP diagnosis.
Education and research
The TTP specialist nurse provides teaching to members of the multidisciplinary team across the hospital trust and wider region to improve knowledge and understanding of TTP as a rare disease. This education is vital in ensuring patients receive timely diagnosis and treatment, to improve survival rates for a little known and recognised condition that may otherwise be missed on presentation to primary care or emergency departments.
In November 2021, the first National TTP Nurses' Network meeting was held in Liverpool, followed in May 2023 by a bespoke simulation training day entitled ‘A Day in the Life of a TTP Specialist Nurse’. These valuable educational events were designed to inform the practice of nurses involved in the care of patients with TTP nationally. TTP specialist nurses are actively engaged in continuous professional development, including involvement in conferences such as the UK TTP Forum, to ensure that they are up to date with best practice guidelines; the forum also offers them the opportunity to disseminate evidence-based practice, thus enhancing the level of care provided to patients.
Audit is also an essential tool in ensuring quality improvement and excellent patient care (Paton et al, 2015). A key role of the TTP specialist nurse is to audit the TTP service against policies and guidelines to ensure that patients are receiving gold standard care in line with current best practice. Examples of audits conducted by specialist nurses within the Liverpool TTP service have included the use of medications such as corticosteroids, rituximab and caplacizumab in the treatment of acute presentation and relapse.
Unfortunately, despite advances in care for patients with TTP over the past 10 years, there are still cases in which aTTP diagnosis can be fatal. By participating in mortality reviews, TTP nurses can identify areas for improvement in future and disseminate lessons learnt throughout the multidisciplinary team. By providing access to research studies the TTP specialist nurse can also ensure that patients are receiving the best possible evidence-based care.
The UK TTP Registry collects important epidemiological data and helps to build a picture of the patient journey in the UK. Other recent studies into TTP have led to National Institute for Health and Care Excellence (NICE) approval of new drugs such as caplacizumab, which has greatly reduced the time to recovery for patients diagnosed with TTP (Dutt et al, 2021). The ongoing study ‘ConNeCT’ is investigating the long-term neurological effects of the condition. Involvement in the study offers patients the opportunity to participate in research that may change the way in which we understand the ongoing disease process of TTP post-initial acute presentation. The specialist nurse's role in supporting patients to participate in research projects is vital, as it provides patients with an opportunity to make a real difference for other patients diagnosed with TTP and can offer access to new drugs and treatments that are not currently available.
Conclusion
TTP specialist nurses play a unique and vital role in providing acute and long-term support to patients with this rare and life-threatening disease. They can offer personalised care to their patients based on an in-depth knowledge and understanding of the disease, and through the development of strong professional relationships. During an acute episode, the TTP specialist nurse acts as co-ordinator to ensure optimum patient care and advocates for patients and helps them to come to terms with their new diagnosis.
In the longer term, TTP specialist nurses form a partnership with their patients to ensure ongoing remission and improved quality of life by taking a holistic, multidisciplinary approach. They engage actively with patients and colleagues to ensure continuous service development and to deliver gold standard care for their patients, helping to improve long-term outcomes and to ensure better survival rates for individuals diagnosed with TTP.
KEY POINTS
- The role of the thrombotic thrombocytopenic purpura (TTP) specialist nurse is critical to ensuring effective interaction between the multiple clinical teams involved in the care of the TTP patient and in supporting patient advocacy
- The role of the TTP specialist nurse extends beyond the initial acute presentation and diagnosis of the patient, and includes providing long-term support, education and follow-up over a period of years
- Patient survey feedback reveals that patients view their specialist nurse as a valuable resource
- The TTP specialist nurse enables the TTP patient to participate in research, and potentially benefit from innovative treatments
- The TTP specialist nurse provides a bridge to help the patient engage with patient support groups
CPD reflective questions
- Consider the role of the thrombotic thrombocytopenic purpura (TTP) specialist nurse. What are the key aspects of the specialist nurse role that contribute to improving care for patients with rare diseases?
- What patient support is available in your area for individuals diagnosed with TTP? What impact does this have on this patient group?