Cell-Free Oxyhemoglobin in Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage: Biomarker and Potential Therapeutic Target

Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by the occurrence of delayed ischemic neurologic deficits (DIND), which impairs the clinical outcome of patients. The release of oxyhemoglobin (oxyHb) from lysing erythrocytes into cerebrospinal fluid (CSF) may critically contribute to the development of DIND.

Methods: Ventricular CSF of 18 high-grade (Fisher 3 and 4) aSAH patients was sampled daily from external ventricular drains between days 0 and 14 after bleeding. CSF was spectrophotometrically analyzed with precise quantification of cell-free oxyHb levels.

Results: OxyHb levels in CSF showed a delayed peak reaching the highest levels in the high-risk period for developing of DIND between days 3 and 14 after aneurysm rupture. Patients with DIND had a significantly higher cumulative oxyHb exposure within the first week after bleeding.

Conclusions: OxyHb levels in CSF may be useful as a biomarker to predict DIND in aSAH patients. The contribution of oxyHb in CSF to the pathogenesis of DIND should be further investigated as a potential therapeutic target.

Keywords: Aneurysm; Biomarkers; Delayed ischemic neurologic deficits; Hemoglobin; Intracranial hemorrhage; Subarachnoid hemorrhage.