Evaluating cerebral microbleeds in paediatric immune thrombocytopenia
File(s)
Author(s)
Hart, Alice Clemency Johnston
Type
Thesis
Abstract
Immune thrombocytopenia is an autoimmune disorder characterised by premature platelet
destruction. Despite low platelet counts, children with ITP rarely have severe bleeding, most
enter early remission, and many do not receive treatment. However, the long-term impact of
ITP in children is not known. Given that occult cerebral microbleeds (CMBs) are seen in adults
with ITP, this study aimed to determine the prevalence of CMBs in children with ITP, and if
there was any impact on patient reported outcome measures (PROMs), and any associations
with platelet function defects.
Fifty children (median age 13.4 years, range 8-18) with ITP (median disease duration 28
months, range 1-129) and at least one platelet count < 30 x 10>9/L were recruited for a study
including MRI brain, PROMs and platelet function studies.
CMBs were identified in 8 patients (16%) (median 2, range 1-10 CMBs) and no controls. CMBs
were significantly related to higher bleeding scores (p=0.008, Mann-Whitney) and days with
platelets <10 x10>9/L (p=0.039). Brain white matter hyperintensities (WMH) were detected in
some patients, currently of uncertain significance.
38% of children were fatigued, 24% had impaired cognition and 50% of children and 78% of
parents had impaired QoL. Fatigue and impaired QoL were more common in females. Fatigue
was correlated with older age at diagnosis (p=0.0012, Spearman correlation) and higher
bleeding scores (p=0.0081). Impaired QoL was correlated with older age at diagnosis
(p=0.014) and lower platelets (p=0.017). CMBs/WMHs were not associated with fatigue,
impaired QoL or cognitive impairment.
Platelet phenomic analysis to assess platelet function demonstrated greater variation in
platelet sensitivity in children with ITP than paediatric controls.
In summary, CMBs, impaired QoL, fatigue and significant parental impact are prevalent in
paediatric ITP. Further study is required to understand mechanisms underlying fatigue and
impaired cognition, and utility of neuroimaging and platelet phenomics for therapeutic
stratification.
destruction. Despite low platelet counts, children with ITP rarely have severe bleeding, most
enter early remission, and many do not receive treatment. However, the long-term impact of
ITP in children is not known. Given that occult cerebral microbleeds (CMBs) are seen in adults
with ITP, this study aimed to determine the prevalence of CMBs in children with ITP, and if
there was any impact on patient reported outcome measures (PROMs), and any associations
with platelet function defects.
Fifty children (median age 13.4 years, range 8-18) with ITP (median disease duration 28
months, range 1-129) and at least one platelet count < 30 x 10>9/L were recruited for a study
including MRI brain, PROMs and platelet function studies.
CMBs were identified in 8 patients (16%) (median 2, range 1-10 CMBs) and no controls. CMBs
were significantly related to higher bleeding scores (p=0.008, Mann-Whitney) and days with
platelets <10 x10>9/L (p=0.039). Brain white matter hyperintensities (WMH) were detected in
some patients, currently of uncertain significance.
38% of children were fatigued, 24% had impaired cognition and 50% of children and 78% of
parents had impaired QoL. Fatigue and impaired QoL were more common in females. Fatigue
was correlated with older age at diagnosis (p=0.0012, Spearman correlation) and higher
bleeding scores (p=0.0081). Impaired QoL was correlated with older age at diagnosis
(p=0.014) and lower platelets (p=0.017). CMBs/WMHs were not associated with fatigue,
impaired QoL or cognitive impairment.
Platelet phenomic analysis to assess platelet function demonstrated greater variation in
platelet sensitivity in children with ITP than paediatric controls.
In summary, CMBs, impaired QoL, fatigue and significant parental impact are prevalent in
paediatric ITP. Further study is required to understand mechanisms underlying fatigue and
impaired cognition, and utility of neuroimaging and platelet phenomics for therapeutic
stratification.
Version
Open Access
Date Issued
2024-10-04
Date Awarded
01/02/2025
License URL
Advisor
Cooper, Nichola
Waldman, Adam
Sponsor
National Institute for Health Research (Great Britain)
Grant Number
NIHR Grant - P8146
Publisher Department
Department of Immunology and Inflammation
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)