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International Journal of Stroke 18(4)
Population-based studies have analyzed the outcomes of
patients with ITP, mostly focusing on White races, with a
lack of data on Asian patients. At present, there are four
population-based studies that explored the outcomes
between patients with and without ITP, and only one study
examined stroke risk.10-13 Enger et al.11 described the
ischemic stroke risk between 3131 ITP and 3131 non-ITP
patients in the United States. The other two studies were
conducted in the United Kingdom, while another combined
study was conducted with Denmark, Norway, and Sweden.13
The novelty of this study is that this is the only Asian population-based
study to focus on overall and different stroke
risk between patients with and without ITP.
Multifactorial mechanisms have been reported to
explain the increased stroke risk in patients with ITP. The
best-known explanation is that platelet microparticles
(PMPs) are released by activated and damaged platelets,
which subsequently promote thrombosis formation in
patients with ITP. Patients with ITP who experienced
ischemic stroke or transient ischemic attack (TIA) are
reported to have higher serum PMP levels.14,15 Furthermore,
a positive association between serum PMP level and intracranial
artery stenosis severity has been reported.16
The susceptibility to bleed in ITP patients are not only
due to low platelet count but also poor platelet function.
Patients with ITP differ in their bleeding tendency under
similar low platelet count.17 ITP patients with poor platelet
function and lower platelet activation response were associated
with higher risk of bleeding.17
Guidelines regarding stroke prevention and management
of acute ischemic stroke in patients with ITP are lacking.
In our subgroup analysis of patients without using
aspirin, ITP patients had 1.35 times higher risk of overall
stroke than those without ITP (Table 2). However, conclusive
recommendation about primary prevention with aspirin
in ITP cannot be made. Meanwhile, recent literature
review examining 27 ITP patients with acute ischemic
stroke, and only one patient received acute perfusion therapy.18
There were also no conclusion about reperfusion
therapy in ITP patients with acute ischemic stroke. Future
large-scale prospective study is needed to better understand
the benefit and risk of prevention and perfusion therapy of
acute stroke in ITP.
There was one novel finding in our stratified analyses.
Individuals with ITP not only had a higher risk of overall
stroke than those without ITP in all age quartiles, but also
possessed nearly fourfold and threefold increased risk of
overall stroke in individuals aged 20-29 and 30-39 years,
respectively. No other study has compared the stroke risk
between individuals with ITP and those without ITP at a
young age. We speculated that the reason for highest risk of
stroke in the younger age group was probably that young
people are usually at very low risk of stroke and stroke risk
in general rises with age. If ITP raises the risk of stroke to
the same extent in young and old people, the increase in
International Journal of Stroke, 18(4)
risk will still be relatively higher in a cohort that is at low
risk of stroke (the young cohort) than in a cohort that is at
higher risk of stroke (the old one).
A Danish population-based study comprising 5306
splenectomy patients and 53,060 matched controls reported
that individuals who underwent splenectomy had nearly
twice the risk of ischemic stroke than those in the matched
cohort.19 A similar association was also observed in our
study.
Our study has four limitations. First, as in retrospective
study, there were inevitable inherent residual bias in the
selection, information, and detection of this study, and we
have adjusted high-dimension variables in the sub-distribution
hazard model to reduce measurable bias and multiple
sensitivity analyses to make our results more reliable.
Second, the sum of ischemic and hemorrhagic events did
not exactly equal to overall stroke events, because patients
experienced multiple events were identified based on earliest
event in overall stroke. This may lead to underestimate
overall stroke incidence. Third, this was an observational
study and could not prove causality. Finally, despite the
homogeneity in the population in this study, the results may
not apply to all ethnicities.
Conclusion
Patients with ITP have an increased risk of overall, hemorrhagic,
and ischemic stroke. When managing patients with
ITP, physicians should be aware of the Janus features of
ITP and extend this concept to plans of treatment and
prevention.
Acknowledgements
The authors are grateful to the Health Data Science Center, China
Medical University Hospital for providing administrative, technical,
and funding support.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study is supported in part by the Ministry of Science and
Technology (MOST 111-2321-B-039-005),
China
Medical
University Hospital (DMR-111-105). The funders had no role in
the study design, data collection and analysis, decision to publish,
or preparation of the manuscript. No additional external funding
was received for this study
ORCID iDs
Renin Chang
Yao-Min Hung
https://orcid.org/0000-0003-1016-2233
https://orcid.org/0000-0001-6920-8799
https://www.orcid.org/0000-0003-1016-2233 https://www.orcid.org/0000-0001-6920-8799
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