One day at a time: Life with Glanzmann thrombasthenia - Qualitative results from the GT 360 study.

Study design : Kate Khair and Michael Holland. Ethical approval : Kate Khair and Simon Fletcher. Interviews and analysis : Simon Fletcher and Kate Khair. Interview transcription : Kathryn Jenner. Manuscript writing, amendment and approval : Kate Khair, Simon Fletcher, Kathryn Jenner, and Michael Holland.

The study was approved by the Health Research Authority and Health and Care Research Wales (22/SC/0095) and registered with ClinTrials.gov ( NCT05315232 ) and the United Kingdom National Institute of Health Research (HAEM 52408). The survey was completed following on‐line consent, written consent was given before the interviews commenced.

All participants consented to their anonymised data being used in any presentation or publication.

Glanzmann's 360 is a mixed methods study including a quantitative survey and a qualitative interview‐based programme. The survey collected data on demographics, symptoms, diagnosis, QoL, psychosocial impact and treatment history, and included a panel of validated assessment tools. People aged over 18 years with GT and parents/carers of children with GT were eligible to participate. Potential participants were identified via treatment centres and were sent study information postcards containing a QR code link to the survey. On completion of the survey, participants were offered the opportunity to take part in a qualitative in‐depth interview. Interview participants were purposively selected to obtain a range of ages, genders, geographical location, and affected individuals versus parents/carers. Written consent was obtained prior to each single interview, which was undertaken via an online platform by two study team members (S.F. and K.K.) who are male and female respectively and are both experienced qualitative researchers who coded the data. All participants received an honorarium. Interview data are reported here; survey data will be reported elsewhere.

Thirty‐three survey participants indicated willingness to be interviewed; of these 19 participated (Figure  1 ). The participants, all residents of the UK or Europe, represented a diverse demographic profile as summarised in Table  1 . Interviews were completed between July 2022 and April 2023 and lasted an average of 45 min. Participant flow chart. Demographic characteristics of interviewed participants. Note : None of the parents ages have been recorded; Participants 360‐14 and 360‐020 withdrew prior to interview. From the analysis of the interviews eight themes emerged: diagnosis, bleeding and treatment, menstruation, fatigue, identity, abuse, pregnancy, and the future (Figure  2 ). Illustrative direct participant quotes for each theme are included below and additionally supporting quotes can be found in Table  2 . NVivo sunburst reflecting the eight themes which emerged in the study. Each subsection represents a descriptive point discussed by participants, coded into eight overarching themes. D&C, dilatation and curettage; IUcD, intra uterine contraceptive device; TXA, tranexamic acid. Participant quotes supporting the themes identified. In all cases, bleeding episodes began soon after birth and most participants were diagnosed by the age of 2 years, usually following referral to a specialist haematology centre. Three of the oldest adult participants described how they had initially been diagnosed as having von Willebrand's disease, haemophilia B or just ‘thrombasthenia’. The paediatrician thought it was like haemophilia … they said they thought it might be something called Christmas disease. [360‐09] The paediatrician thought it was like haemophilia … they said they thought it might be something called Christmas disease. [360‐09] For these three participants, formal diagnosis of GT came in their teens or twenties. Parents of children in this study with GT reported early recognition and prompt diagnosis. Bleeding sites reported by participants are summarised in Table  3 . The most commonly reported symptom was bruising (18/19 participants). Bruises attracted attention from others, sometimes leading those affected to modify their clothing choices. Nose bleeds (16/19) and other mucosal bleeding (12/19) were also common, particularly in childhood, causing distress for parents. Older participants (age range 33–64 years) frequently accepted bleeding from mucous membranes as ‘normal for them’. Less commonly reported were joint bleeds (6/19) and gastro‐intestinal bleeds (5/19). Bleed sites reported by participants. Abbreviations: −, no; +, yes; N/A, not applicable; PPH, postpartum haemorrhage. If applicable based on age and gender. Most interviewees received treatment in hospital with recombinant activated factor VII (rFVIIa) (17/19), platelets (15/19) and blood transfusion (9/19). For some participants, limited clinical expertise in local hospitals (whether due to lack of testing facilities and/or understanding of treatment) meant long journeys to attend specialist hospitals. One thing we found out with our local hospital is that they can't do any treatment, so it was having to go to [specialist hospital] all the time. [360‐07] One thing we found out with our local hospital is that they can't do any treatment, so it was having to go to [specialist hospital] all the time. [360‐07] While most (18/19) had treatment at home this was generally limited to tranexamic acid (18/19); six participants were able to self‐infuse (rFVIIa). All post‐menarche women (11/19) reported HMB; five reported menarche as traumatic, characterised by prolonged bleeding and hospitalisation for transfusions. I ended up in hospital because I had a period that went on for months. [360‐02] I ended up in hospital because I had a period that went on for months. [360‐02] Alongside haemostatic therapies for HMB, women were prescribed hormonal therapies to control/stop menstruation. Those considering pregnancy reported concern from healthcare professionals about the implications of stopping hormone therapy; others were less concerned. One participant's consultant had told her to ‘just stop taking the pill and we will see what happens ’ [360‐05]. Blood loss caused by frequent, often daily bleeding from mucous membranes often resulted in chronic anaemia and fatigue, causing significant impact on lifestyle. It's really, really, really tough for me to do anything outside of get up, go to bed, come back home or sleep. [360‐08] It's really, really, really tough for me to do anything outside of get up, go to bed, come back home or sleep. [360‐08] Many participants found oral iron supplementation burdensome (8/19), with unwanted side effects leading to non‐ or reduced adherence and uncorrected anaemia. Some participants expressed a preference for parenteral iron infusions. Ten participants spoke about their identity as people with GT, describing it as an important but not defining part of themselves. Two thought GT affected the way they interacted with the world and understood themselves. One described how a very protected and restricted childhood had affected her. I left school as an extremely shy, timid, no confidence, no self‐esteem, very sort of… can't really get very far in the world because I've got GT and I'm fragile. [360‐05] I left school as an extremely shy, timid, no confidence, no self‐esteem, very sort of… can't really get very far in the world because I've got GT and I'm fragile. [360‐05] Six described controlling who knew about their diagnosis as a way of regaining control of their life. When I've been employed, I've not let anybody know. Only closest friends, just to say if I'm ever in an accident and I'm unconscious, you need to know this. [360‐11] When I've been employed, I've not let anybody know. Only closest friends, just to say if I'm ever in an accident and I'm unconscious, you need to know this. [360‐11] Two participants felt their GT defined them. If you remove the Glanzmann's it's like taking away a component of [me], I've lived with it all my life. In a sense it's defined a part of me. [360‐03] If you remove the Glanzmann's it's like taking away a component of [me], I've lived with it all my life. In a sense it's defined a part of me. [360‐03] Participants reported how bruising frequently led to questioning from others. The embarrassment if you were out swimming or anything at school, that was one of the things. You always get people staring. [360‐011] The embarrassment if you were out swimming or anything at school, that was one of the things. You always get people staring. [360‐011] For some participants, both adults and children, bruising had led to others inferring they had sustained a non‐accidental injury. We always had social workers round because people used to think that mum or dad was beating me up …. that was really hard for them. [360‐09] We always had social workers round because people used to think that mum or dad was beating me up …. that was really hard for them. [360‐09] Several women described how doctors had advised them against pregnancy, in one case before menarche. My mum and dad were told I'd never have a family. ‘Tell her not to even think about it because she won't survive.’ [360‐05] My mum and dad were told I'd never have a family. ‘Tell her not to even think about it because she won't survive.’ [360‐05] Another participant was told at age 13, ‘that childbirth would be bad’ [360‐13]. This ‘medical pessimism’ persisted and meant that some women chose not to attempt pregnancy, which impacted relationships. However, five women had had children; all reported PPH despite medical management at delivery. Further pregnancy was reported as too risky either for themselves or their baby. Two participants felt that little effort was being put into developing new treatments for GT in comparison with other bleeding disorders. I did hear on the news, I think it was a few months ago, about a new drug or something for haemophilia. But that was nothing to do with Glanzmann's, unfortunately, which is a shame. [360‐08] I did hear on the news, I think it was a few months ago, about a new drug or something for haemophilia. But that was nothing to do with Glanzmann's, unfortunately, which is a shame. [360‐08] However, some participants remained hopeful that the future would bring better treatment options. I know that innovation is coming and that there is a lot going on in the world. [360‐16] I know that innovation is coming and that there is a lot going on in the world. [360‐16] There was also a willingness to participate in clinical trials, even where direct benefit was not guaranteed. Even if it doesn't benefit us it's going to benefit people who are diagnosed later on. [360‐09] Even if it doesn't benefit us it's going to benefit people who are diagnosed later on. [360‐09]

Each participant was assigned a study number (e.g., 360‐01) for anonymity. After each interview, audio files were transcribed verbatim and coded for analysis using NVivo for Mac (version 12). Themes were identified using grounded theory, analysed and synthesised and a descriptive framework was developed. 6 Emergent themes were reviewed and refined following each interview to enable further exploration in subsequent interviews. Field notes were made following each interview and used to provide context to the coding. This iterative process was continued until no new themes were described (data saturation). Five interviews were then randomly selected for manual coding and compared with the primary analysis to ensure accuracy and reliability of the codes.

This study highlights a number of unmet needs for people with GT, including difficulty in initiating prompt, effective bleed treatment, the lack of prophylactic therapy, and management of anaemia and fatigue. For women there are under‐appreciated psychological issues around reproductive choices that warrant further attention. Areas for further research include the impact of living with someone with GT on family members, treatment of anaemia, side effects of iron therapy, and hopes for future GT treatments.

Diagnosis of rare conditions is often complex and challenging, particularly when there is no known family history. GT is often not considered as part of the differential diagnosis and may be misdiagnosed as another bleeding disorder. 7 , 8 Although older participants in our study reported, misdiagnosis, and this appeared to be less of an issue for younger participants. Whether this is due to improved diagnostic testing or increasing awareness of GT is not known. 9 Timely, accurate diagnosis is an essential prerequisite for appropriate management and bleed prevention. 10 In common with findings reported by Duncan et al., 5 many study participants reported a high bleeding frequency which they had normalised. Treatment was often initiated at home with antifibrinolytic therapy, as recommended by UK clinicians 11 , 12 ; participants attended hospital for treatment if this failed to stop bleeding. Many participants preferred to travel to centres with specialist medical expertise rather than accept care from local providers, as others have reported. 9 , 13 Treatment initiation was therefore ‘late’, necessitating treatment with rFVIIa 14 or platelet and/or blood transfusions. Surprisingly, almost one third of study participants reported joint bleeding, echoing other reports in the literature 15 , 16 – reported joint bleeding. Joint bleeds in GT can be difficult to treat. Analgesia use is limited; platelet transfusion and rFVIIa may be required, as may acute physiotherapy assessment. Repeated joint bleeds lead to long‐term arthritic damage and may require musculoskeletal intervention, including orthopaedic surgery. 17 HMB was reported by all women in our study. Treating HMB requires multidisciplinary team collaboration and should reflect age and life stage, involving primary care clinicians as well as specialist services. Recurrent bleeding, even if considered minor and therefore left untreated, results in iron deficiency anaemia (IDA) and fatigue. 18 Several study participants reported on fatigue and its impact on daily life. Blaauwgeers et al. reported that women with platelet disorders and IDA due to HMB having lower levels of social activity and decreased QoL that do not correlate with bleeding scores. 19 Although oral iron therapy is first‐line choice for treating IDA, gastrointestinal side effects are known to impact treatment compliance. 20 Intravenous iron is recommended for those intolerant of or unresponsive to oral therapy 21 and has been shown to reduce the need for blood transfusion 22 and to improve QoL 23 in people with GT. The impact of living with a bleeding disorder on self‐identity remains under‐explored. Studies in haemophilia have begun to examine how individuals perceive their condition in relation to their understanding of who they are. 24 In this and other studies, 4 , 5 participants describe the impact of GT on many areas of life, including school, work, leisure and social activities. Although most participants in this study did not feel defined by their condition, four said living with GT was integral to their self‐understanding. Two indicated that the way they lived, adjusting their lives and behaviours to meet the limitations imposed by GT and the expectations of others, 25 , 26 had made them who they are. However, the paradox of striving to live a ‘normal’ life while being constrained by disease‐related risk avoidance, also reported by Hughes et al. in people living with severe haemophilia, 27 , 28 was evident among many participants. Alongside self‐limiting behaviour, their ‘normality’ involved acceptance of symptoms, including bruising and mucosal bleeding as part of daily life. Given the rarity of GT, few clinicians ever encounter a patient with the condition. In the case of children, this can result in suspicion of non‐accidental injury on presentation with unusual bruising. 29 For people with GT, the impact of bruising extends beyond childhood and the hospital setting, as does the suspicion of abuse. 8 Several female participants said they did not like people to see their bruises for this reason, preferring to wear longer clothes to cover unsightly bruises. However, this could also raise concern, as wearing ‘inappropriate clothing’ in the wrong season can also be an indicator of abuse. 30 Abuse is often thought of as a gender‐specific issue, although UK research suggests 18% of domestic abuse victims are men. 31 None of the men in our study reported concern about the appearance of bruising as adults, or its perceived significance. Even among specialist clinicians, attitudes can impact the lives of people with GT. Only a small number of pregnancies were reported in our study, in part because doctors had deterred some women from the idea of having a child. With greater understanding of GT, and availability of and access to more effective treatments, it is to be hoped that fewer women considering pregnancy today will encounter such ‘medical pessimism’. 32 However, despite recommendations for management of delivery, 3 PPH has been reported in 58% of UK women with GT 2 and may occur as late as 20 days. 33 A careful multidisciplinary approach is necessary to optimise maternal and foetal outcomes. 34 Anaemia is associated with PPH, 35 thus women with GT and anaemia may be at greater risk. Experiencing PPH after a life of HMB appears to have dissuaded women in this study from attempting a second pregnancy. Our interviewees were self‐selected to participate and may represent those with worst bleeding experience and the greatest unmet needs. As such, they may not be representative of the wider GT community, or indeed of the experience of people with GT in other countries. Nevertheless, their accounts suggest a need for improved therapeutic and support options, which may require further education of clinicians specialised in bleeding disorders about the daily impact of living with GT. Non‐specialist local care providers also require education and support from specialist centres to initiate prompt care delivered closer to home, which may have a beneficial impact on treatment initiation and outcomes.

Glanzmann thrombasthenia (GT) is a genetic platelet function disorder caused by absence or reduction of the glycoprotein IIb/IIIa complex on the platelet surface. 1 GT is characterised by a broad spectrum of bleeding from early childhood, including bruising and epistaxis, escalating to potentially life‐threatening bleeding. 2 For females with GT, prolonged heavy menstrual bleeding (HMB) is common 3 and debilitating, and they face elevated risk of peri/post‐partum haemorrhage (PPH). 2 , 3 Despite the acknowledged impact of GT on individuals' quality of life (QoL) by the healthcare community, the literature on the lived experience of people with GT and their caregivers remains sparse, leaving a gap in our understanding and approach to care. 4 , 5 The Glanzmann's 360 study was designed to explore the nuance of the daily lived experiences of those living with or caring for someone with GT.

All authors are employee of Haemnet Ltd.