Usability of serum inter-α-trypsin inhibitor heavy chain 4 as a biomarker for assessing severity and predicting functional outcome after human aneurysmal subarachnoid hemorrhage: A prospective observational cohort study at a single institution

Background: Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) may harbor anti-inflammatory activities. We sought to discern the predictive significance of serum ITIH4 for delayed cerebral ischemia (DCI) and clinical outcomes of human aneurysmal subarachnoid hemorrhage (aSAH).Methods: At a single institution, we performed a prospective and observational cohort study of 148 patients with aSAH and 52 healthy controls. Poststroke six-month extended Glasgow Outcome Scale (GOSE) score of 1-4 was designated as a poor prognosis. Prognosis associations were verified using multivariate analysis.Results: As compared to controls, patients had significantly declined serum ITIH4 concentrations from admission until day 10, with the lowest concentrations at days 1-3 after stroke. Serum ITIH4 concentrations, which were substantially decreased with the increasing Hunt-Hess scores or modified Fisher scores, were independently correlated with the two scores. Moreover, serum ITIH4 concentrations, which were markedly elevated in the order of GOSE scores from 1 to 8, together with Hunt-Hess scores and modified Fisher scores were independently related to GOSE scores and poor prognosis. However, serum ITIH4 concentrations were not independently predictive of DCI. Prediction model of poor prognosis integrating the preceding three variables were delineated using the nomogram, were verified under the calibration curve, and displayed high discriminatory efficiencies under the receiver operating characteristic curve.Conclusions: A significant decline of serum ITIH4 concentrations during the early phase after aSAH was closely related to severity and poor prognosis, assuming that serum ITIH4 may represent a promising prognostic biomarker of aSAH.

Automated summary

This study found that the decline of serum ITIH4 concentrations during the early phase after aneurysmal subarachnoid hemorrhage (aSAH) was closely related to the severity and poor prognosis of the disease. Serum ITIH4 may represent a promising prognostic biomarker of aSAH.