Clinical profiling and outcomes of ischemic stroke patients with immune thrombocytopenia: A multicenter real-world study

Abstract

Abstract Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by platelet destruction mediated by autoantibodies targeting platelet antigens. The primary clinical manifestation of ITP is bleeding, which can range from mild skin/mucosal hemorrhage to life-threatening bleeding in vital organs. However, some patients also face an increased risk of thrombosis/embolism. Embolic events in critical organs, such as the heart and brain, can severely impact patient quality of life and lead to life-threatening complications. Epidemiologically, acute ischemic stroke (AIS) is a globally prevalent disorder that substantially compromises quality of life and physical health across populations. Research has suggested that ITP increases the risk of cerebral infarction, representing a relatively rare etiological factor for AIS. Methods This was an observational multicentric study，both prospective and retrospective，performed to collect data on patients with ITP-AIS. We evaluated consecutive adult ITP-AIS patients hospitalized from January 2008 to July 2025 at 9 different Chinese medical centers. Results A total of 90 ITP patients were included; the median age was 63 years (range: 24–90), with 51 males and 39 females. AIS occurred at a median ITP disease duration of 1.92 years (range: 0.01–48). Using the Oxfordshire Community Stroke Project (OCSP) classification system, we found that among the stroke subtypes, 38 patients (42.2%) had lacunar infarcts, whereas 26 patients each (28.9%) presented with anterior and posterior circulation infarcts. According to NIH Stroke Scale (NIHSS) assessments, stroke severity was distributed as follows: 59 patients (65.6%) had mild strokes, 26 (28.9%) had moderate strokes, and 5 (5.5%) had moderate-to-severe strokes. Univariate analysis revealed that thrombopoietin receptor agonists (TPO-RAs) use (P=0.049; HR 5.74; 95% CI 1.01-32.54), anterior circulation infarction (P=0.006; HR 7.19; 95% CI 1.75-29.48), and posterior circulation infarction (P=0.034; HR 4.60; 95% CI 1.12-18.87) were significant risk factors for at least moderate stroke. Multivariate analysis further revealed that both anterior (P=0.016; HR 5.93; 95% CI 1.39-25.22) and posterior circulation infarction (P=0.046; HR 4.28; 95% CI 1.02-17.93) were independent risk factors for at least moderate strokes. Among 90 patients with ITP-AIS, 11 (12.2%) presented with thrombosis at sites other than the cerebral infarction, including 1 patient with pulmonary embolism, 6 with lower extremity deep vein thrombosis, 1 with cardiac thrombosis, and 3 with myocardial infarction. Postinfarction treatment included antiplatelet therapy in 25 patients (27.8%), anticoagulation therapy in 3 patients (3.3%), and combined antiplatelet-anticoagulation therapy in 6 patients (6.7%). No patients received tissue plasminogen activator (tPA) or endovascular thrombectomy (EVT). Hemorrhagic transformation occurred in 5 patients (5.6%), all of whom were not receiving antithrombotic therapy; 2 patient (2.2%) died respectively due to intracranial hemorrhage and infection. Compared with 270 ITP patients without AIS, those with AIS were older and had higher incidence rates of hypertension, diabetes, and chronic kidney disease; elevated blood cholesterol levels; higher smoking rates; higher platelet counts at AIS or at the last hospital visit; and lower rates of immunosuppressive therapy within one month before AIS or at the last hospital visit. Multivariate analysis revealed that hypertension (P<0.001; HR 4.99; 95% CI 2.63–9.47), diabetes (P=0.005; HR 2.65; 95% CI 1.35–5.20), chronic kidney disease (P=0.002; HR 4.96; 95% CI 1.76–14.01), smoking (P=0.012; HR 3.39; 95% CI 1.40–8.20), and a platelet count >20×10⁹/L (P=0.039; HR 1.99; 95% CI 1.04–3.84) were independent risk factors for AIS in ITP patients. Conclusions The risk factors for ITP-AIS include common cerebrovascular risk factors such as hypertension, diabetes, chronic kidney disease, and smoking, as well as elevated platelet counts. In contrast, ITP treatments, including danazol, immunoglobulins, rituximab, splenectomy, and TPO-RAs, had no significant effect on the incidence of post-ITP cerebral infarction. Currently, the management of AIS in ITP patients requires close collaboration between hematologists and vascular neurologists to carefully balance therapeutic benefits against the risk of hemorrhagic complications.