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Quality of life in immune thrombocytopenia following treatment
  1. John D Grainger1,
  2. Nancy L Young2,
  3. Victor S Blanchette3,
  4. Robert J Klaassen4
  1. 1Department of Haematology, University of Manchester, Royal Manchester Children's Hospital, Manchester, UK
  2. 2School of Rural and Northern Health, Laurentian University, Sudbury, Ontario, Canada
  3. 3Hospital for Sick Children, Toronto, Ontario, Canada
  4. 4Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  1. Correspondence to Dr John D Grainger, Department of Haematology, University of Manchester, Royal Manchester Children's Hospital, Ward 84, Manchester M13 9WL, UK; john.grainger{at}cmft.nhs.uk

Abstract

Objective To determine the impact of therapy on the reported health-related quality of life (HRQoL) in children with primary immune thrombocytopenia (ITP) using the Kids ITP tool (KIT).

Design Secondary data analysis of the international and North American KIT validation studies.

Results 217 children from 6 countries participated in the two studies. The majority of treatments occurred in children with newly diagnosed ITP. There was no statistical difference in age, platelet count and bleeding severity at presentation in those who physicians chose to treat or observe. Self-reported KIT scores did not differ between the two groups. The KIT parent-proxy scores were significantly worse for newly diagnosed children receiving treatment, especially following prednisone.

Conclusions Treatment of ITP does not improve, and may worsen, the HRQoL of children with ITP as measured using the KIT.

  • Haematology
  • General Paediatrics
  • ITP
  • quality of life

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What is already known on this topic

  • Health-related quality of life is an important outcome measure for children with ITP.

  • The majority of children with ITP do not have significant bleeding and recover spontaneously.

What this study adds

  • Health-related quality of life is not improved by treatment.

  • The side effects of treatment can negatively impact on health-related quality of life.

Introduction

Primary immune thrombocytopenia (ITP) is an antibody-mediated thrombocytopenia, with a platelet count <100×109/L, in the absence of any underlying cause. The majority of children do not have severe bleeding and will spontaneously recover within a few weeks. However, many children face lifestyle restrictions to minimise the risk of bleeding. Treatment of ITP may lessen the bleeding risk but the side effects of treatment can be considerable. This short report focuses on a comparison of health-related quality of life (HRQoL) between children managed with therapy to increase the platelet count and children monitored without therapy.

Methods

The Kids ITP tool (KIT) is an ITP-specific HRQoL measure that was initially developed and tested in North America and subsequently developed for use in other languages and cultures.1 ,2 The measure used consists of 2 questionnaires: 1 version for the child, age 7–17.99 years (child self-report) and another for the parent to complete on behalf of the child, age 2–17.99 years (parent proxy-report). KIT scores have a possible range of 0 (worst) to 100 (best).

Children aged 2–18 years were recruited from 11 treatment centres, across six countries, with specialist expertise in the management of childhood ITP. The countries participating were Canada, France, Germany, UK, USA and Uruguay. Children ≥7 years were asked to complete a self-report KIT, and parents completed a proxy KIT for all children. Ethical approval was obtained in each country and informed consent obtained for each participating family or child.

The data presented was obtained during the validation testing of the North American and International KIT. The KIT was validated following completion of these studies with no alteration to the KIT. The data presented here has not been previously described in the validation studies.

Newly diagnosed ITP was defined for these studies as duration of ITP <3 weeks. The KIT was administered within 14 days of diagnosis for these patients. All treated patients had completed treatment at the time of the KIT. Chronic ITP was defined as duration of ITP >6 months after presentation. Persistent ITP was defined as ITP 4–26 weeks duration. Treatment data was collected prospectively as part of the studies, bleeding severity was graded by physicians according to the Buchanan bleeding score as previously described.3 The decision to treat was left entirely up to the physician in discussion with the family.

Results

Demographics

There were 217 children were recruited to the study. The median age was 9.7 years (2.0–18.0), 76 children were aged under 7 years; 87 children were newly diagnosed, 6 persistent and 124 in the chronic phase of ITP.

Treatment episodes

Totally, 119 children (55%) were managed by observation alone and 87 received therapy to increase the platelet count (32 intravenous immunoglobulin (IVIG), 32 prednisone, 9 IVIG and steroids combined, 12 anti-D, 1 rituximab, 1 splenectomy). Data was unavailable for 10. Only 28 treatment episodes (28 of 124 children) took place in children with chronic ITP and three treatments (three of six) in the persistent phase. The remaining 56 treatment episodes (56 of 87) were within 14 days of presentation (27 IVIG, 18 prednisone, 6 combined, 5 anti-D). This data and subanalysis by disease phase and intervention is presented in table 1.

Table 1

Patient characteristics

There was no statistical difference in age, gender or platelet count between children receiving treatment and those managed with observation. There was a trend toward higher bleeding severity in the treatment group but it did not achieve statistical significance (p=0.056).

In all countries, the majority of children were managed by observation alone. When treatment was administered, North America and Germany were more likely to use IVIG, while UK, France and Uruguay favoured steroids.

Health-related quality of life

The patient self-report KIT was completed by children over 7 years of age. Lower KIT scores were demonstrated in newly diagnosed ITP compared with chronic ITP. This has been previously described in North American and international study, and is of statistical significance (p=0.005).1 ,2

There is no statistical difference evident between groups treated and untreated in newly diagnosed and chronic phases of disease. The proxy KIT was reported for all the children, and demonstrated a statistically significant (p=0.03) lower KIT scores for newly diagnosed children receiving treatment. When we compared treatment modalities in the newly diagnosed phase, we found that the lowest HRQoL score was observed in those children treated with prednisone. This data is presented in figure 1.

Figure 1

Kids ITP (primary immune thrombocytopenia) tool (KIT) score of newly diagnosed patients.

Discussion

Patient-reported outcomes are important outcome measures especially in diseases such as ITP where the rate of mortality and severe morbidity is low. Severe bleeding is fortunately rare in ITP with a reported incidence of 3%.3 Other outcome measure in ITP are unreliable, as the platelet count is not predictive of bleeding as illustrated by the majority of patients having minimal bleeding despite a platelet count often below 20×109/L.

The decision to treat or to monitor patients with ITP has been a frequent topic of debate. In the UK, the majority of children are now managed without intervention which reflects UK guidelines.4 The group presented here includes many patients from North America which has historically had a more interventional approach based on platelet count. More recent international guidance now favour that those children with absent or minor bleeding should not be treated regardless of platelet count.5

The reasons to hold off treatment are based on observational data that suggest that the majority of children will not have severe bleeding even with severe thrombocytopenia, and that the platelet count will often show signs of recovery within a few days and be back to normal within a few weeks. When treatment is given, platelet recovery is more rapid which may be important if active bleeding is present. The commonest treatments used are steroids and IVIG. The side effects of these drugs have been previously well described and may be considerable.

The KIT has 26 questions which includes questions on symptoms and patient worry. While treatment may increase the platelet count if bleeding was minimal, then no clinical benefit may be observed by the family. It is hypothesised that the worse QoL reported by parents following treatment may be a combination of increased worry about future bleeding events, side effects of medicine, and increased hospital visits.

The North American, international and the combined data presented here demonstrate lower HRQoL scores in the newly diagnosed patients versus those in the chronic phase of the disease.1 ,2

Since the majority of patients with newly diagnosed ITP received therapy, whereas the majority of chronic ITP patients were monitored, a comparison of HRQoL by intervention is only possible within the specific disease phase. A limitation of this study is that individual KIT scores are not available before and after treatment.

The analysis shows no statistical significant difference in platelet count, bleeding severity or age of patient between those treated and not. There was a trend for bleeding severity to be greater in those treated which is consistent with treatment recommendations; however, the majority of treated and untreated patients both had minimal bleeding. Severe bleeding is fortunately rare in ITP, and subanalysis of those with severe bleeding events would require a much larger study.

The failure of treatment to improve HRQoL reinforces the fact that an improvement in platelet count may be counter balanced by the side effects of treatment. Patient-reported outcome measures are a vital outcome measure to improve our understanding of the benefits and side effects of intervention. Future studies and registry data should include HRQoL as an important outcome measure and explore the possible reasons for failure of treatment to improve HRQoL. Ideally, HRQoL should be recorded before and after any treatment is administered.

Acknowledgments

Victoria E Price, Christine Curtis, Cindy Wakefield, Tricia A Burke, Gustavo Dufort, Gerhard Gaedicke, Arne Riedlinger, Christophe Soltner, Estela Citrin, Yves Reguerre, Isabelle Pellier, Cindy E Neunert, George R Buchanan, Dorothy Barnard were all involved locally with the administration of the KIT at their local sites.

References

Footnotes

  • Collaborators Victoria E Price, Paula H B Bolton-Maggs, Christine Curtis, Cindy Wakefield, Tricia A Burke, Gustavo Dufort, Gerhard Gaedicke, Arne Riedlinger, Christophe Soltner, Estela Citrin, Yves Reguerre, Isabelle Pellier, Cindy E Neunert, George R Buchanan.

  • Contributors JDG: acquisition and analysis of data, drafting of manuscript. NLY: design of study, analysis of data, revision of manuscript. VSB: design of study, revision of manuscript. RJK: design of study, acquisition and analysis of data, drafting of manuscript. All authors have given their final approval of this version of the manuscript to be published.

  • Funding This research was conducted with the support of unrestricted grants from Cangene Corporation and the UK ITP Support Association.

  • Competing interests None.

  • Ethics approval The local country ethics and individual site review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.