Abstract Body: Background
There is an emerging understanding of stroke risk in patients with immune thrombocytopenia purpura (ITP) and immune thrombotic thrombocytopenia purpura (iTTP). We aimed to determine the prevalence of acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) in patients with ITP and iTTP in a systematic review and meta-analysis.

Methods
We used PubMed, Embase, Cochrane, Web of Science, and Scopus using text related to ITP, iTTP, stroke, AIS, and ICH from inception to 11/3/2023. Our primary outcome was to determine prevalence and chronicity of AIS and/or ICH in a cohort of ITP or iTTP patients (age >18). Our secondary outcomes were to determine stroke associated with thrombopoietin receptor agonists (TPO-RAs) in ITP patients and risk factors associated with stroke in ITP and iTTP patients.

Results
We included 42 studies with 118,019 patients (mean age=50 years, 45% female). Of those, 27 studies (n=116,334) investigated stroke in ITP patients, and 15 studies (n=1,685) investigated stroke in iTTP patients. In all ITP patients, the prevalence of AIS and ICH was 2.1% [95% Confidence Interval (CI) 0.8%-4.0%] and 1.5% (95% CI 0.9%-2.1%), respectively. ITP patients who experienced stroke as an adverse event from TPO-RAs had an AIS prevalence of 1.8% (95% CI 0.6%-3.4%) and an ICH prevalence of 2.0% (95% CI 0.2%-5.3%). Prevalence of stroke did not significantly differ between all ITP patients and those treated with TPO-RAs. iTTP patients had a prevalence of AIS and ICH of 13.9% (95% CI 10.2%-18.1%) and 3.9% (95% CI 0.2%-10.4%), respectively.
Subgroup analysis revealed the prevalence of AIS and ICH was greater in iTTP patients vs. all ITP patients (p<0.01 and p=0.02, respectively). Stroke occurrence was reported in the acute phase (7.9% and 45%) and chronic phase (91.8% and 55%) in ITP patients (not specifically due to TPO-RAs) and iTTP patients, respectively. Meta-regression analysis revealed none of the collected variables (age, sex, history of diabetes or hypertension) were risk factors for stroke in all ITP patients, although there were high levels of data missingness.

Conclusions
Prevalence of stroke was lower in all ITP patients vs. iTTP patients. ITP patients experienced a similar prevalence of stroke regardless of if they were specifically denoted to have been treated with TPO-RAs or not, supporting the continued use of TPO-RAs in management. Risk factors for stroke remain unclear, and future studies should continue to investigate this relationship.