The HeMoVal Study: A Multicenter Validation of Cerebrospinal Fluid Hemoglobin as Monitoring Biomarker for Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage

Introduction: Preclinical investigations and a single-center pilot study linked cerebrospinal fluid hemoglobin (CSF-Hb) to secondary brain injury after subarachnoid hemorrhage (SAH-SBI). The primary objective of the HeMoVal study was to prospectively validate the association between external ventricular drain (EVD) CSF-Hb and SAH-SBI. Secondary objectives included assessing the discriminatory ability of both EVD and lumbar drain (LD) CSF-Hb and defining a clinically relevant toxicity threshold.

Methods: The HeMoVal study was a prospective international biomarker validation involving adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH). All aSAH patients were eligible for inclusion with a target of 250 patients with EVD samples. Baseline epidemiologic and disease-specific measures were assessed at inclusion. Patients with EVD or LD had daily CSF samples collected during the first 14 days, followed by assessments for SAH-SBI, co-interventions, and complications. A three-month follow-up was conducted. The cohort was stratified into EVD, LD, and full cohort for analysis. The study was preregistered on ClinicalTrials.gov (NCT04998370). The protocol and statistical analysis plan were published at initiation (https://doi.org/10.1186/s12883-022-02789-w).

Results: From August 2021 to July 2024, we enrolled 366 patients across eight centers in Switzerland, Germany, and Austria – 259 patients with at least one EVD sample and 66 with at least one LD sample. At AANS2025, we will present the primary and key secondary results of the HeMoVal study based on 2,460 EVD and 378 LD samples. The primary analysis quantifies the association between EVD CSF-Hb and SAH-SBI using a generalized additive model. Secondary analyses evaluate the association between LD CSF-Hb and SAH-SBI and assess the discriminatory ability of CSF-Hb via receiver operating characteristic (ROC) analyses.

Conclusion : We will present the results from the international HeMoVal study, which aimed to validate CSF-Hb as a biomarker to monitor for SAH-SBI and to establish an intervention threshold to target CSF-Hb toxicity.