Outcome and recovery trajectories for intracerebral hemorrhage in adults with primary immune thrombocytopenia

Abstract Introduction Intracerebral hemorrhage (ICH) is a rare but devastating complication of immune thrombocytopenia (ITP). Current knowledge is limited in terms of the clinical features and outcome trajectories for ICH in adults with primary ITP. We previously conducted preliminary work to predict mortality risk in patients with intracranial hemorrhage (Blood Adv, 2022), but the role of neuroimaging indicators and long-term outcomes was not evaluated. Here, we report a multicenter cohort study to explore the clinical characteristics, prognostic profiles, and recovery trajectories of adult patients with ICH. Methods Adult patients with ITP who developed ICH between January 2010 and December 2022 were retrospectively identified from 43 medical centers in China. Patients fulfilling the following criteria were included in this study: 1) a clinical diagnosis of primary ITP; 2) a diagnosis of ICH confirmed by imaging evidence; 3) ICH occurring at or after the diagnosis of ITP; 4) age over 18 years at the time of ICH diagnosis; and 5) available 30-day outcomes. Demographic information, clinical manifestations, and follow-up data were retrieved from the medical records. Neuroimaging indicators were reviewed by neurosurgery and radiology specialists at Peking University People's Hospital. Candidate predictors for 30-day mortality after ICH were included in the multivariate analysis using a forward stepwise logistic regression model. Variables remaining in the final model were determined to be independent predictors. The study protocol was approved by the central institutional review board of Peking University People's Hospital. Results One hundred sixty-six (166) patients were included in this study. Patients developed ICH at a median age of 56.5 (IQR, 39.75-67) years, and 109 of them were female. The median platelet count at ICH onset was 7×109/L (IQR, 3-22×109/L). Forty-four (44) patients had underlying diabetes and 36 patients had underlying hypertension at the time of ICH diagnosis. Twenty-eight (28) patients (16.9%) were receiving anticoagulant therapy for underlying atrial fibrillation, and these patients had significantly higher median platelet counts at ICH onset (median, 49.5×109/L vs. 6×109/L, p <0.001). Most patients had deep ICH (65.1%), followed by lobar (25.9%) and infratentorial (13.9%) ICH. A hematoma volume exceeding the previously reported location-specific cutoff for mortality risk (Stroke, 2023) was present in 32 (29.6%) patients with deep ICH, 16 (37.2%) patients with lobar ICH, and 8 (53.3%) patients with infratentorial ICH. Seventy (70) patients (42.2%) died during a median follow-up of 512 (IQR, 12-1871) days, among whom 56 patients (33.7%) died within 30 days of ICH diagnosis. In the multivariable analysis, infratentorial ICH (p =0.001), hematoma volume exceeding the location-specific cutoff for mortality risk (p <0.001), concurrent organ or life-threatening bleeding (p =0.006), and underlying diabetes (p =0.014) were identified as independent risk factors for 30-day mortality. Nineteen (19) patients developed recurrent ICH; the median time of onset was 396 (IQR, 144-1298) days after the first ICH episode. Among the patients with recurrent ICH, 7 (36.8%) were refractory to both corticosteroids and thrombopoietic receptor agonists, and 8 (42.1%) were receiving anticoagulant therapy for atrial fibrillation. Among the 30-day survivors, 6 patients were lost to follow-up and 14 patients died within 1 year of ICH diagnosis. Eighty-one (81) patients with baseline functional impairment (a 30-day modified Rankin Scale score of 3-5) had available functional data at the 1-year follow-up, and 35 (43.2%) of them achieved functional recovery (a 1-year modified Rankin Scale score of 0-2). The female sex (p =0.045) and concurrent organ or life-threatening bleeding within 30 days of ICH diagnosis (p =0.046) were associated with significantly lower probabilities of 1-year functional recovery (multivariable logistic analysis adjusted for age, ICH location, hematoma volume, hypertension, and diabetes). Conclusions In adults with ITP who developed ICH, neuroimaging indicators, bleeding diathesis, and underlying diabetes played key prognostic roles. Anticoagulant use and treatment refractoriness were associated with recurrent ICH. Among survivors of severe ICH, 43.2% achieved functional recovery at 1 year.