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Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage

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Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH.


Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6 months.


One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61 U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4–5) and mild clinical condition (72 vs. 63 U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3–4) compared to those with mild radiologic status (77 vs. 61.5 U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95% CI 1.002–1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95% CI 1.001–1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95% CI 1.041–1.127, p < 0.001). Trend analysis of ALP level based on 103 patients’ data revealed a significant decrease in ALP level on post-admission day 7–9 (median; on-admission day vs. post-admission day 7–9, 72 vs. 60 U/L, p = 0.0012; post-admission day 3–5 vs. day 7–9, 70 vs. 60 U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12–14 (median, 84 U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3–5, and 12–14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67 U/L, p = 0.0122; post-admission day 3–5, 80 vs. 64 U/L, p = 0.0044; post-admission day 7–9, 75 vs. 53.5 U/L, p < 0.0001) but not on post-admission day 12–14.


Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.

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The authors thank all stuff in Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, for their technical support. This study was supported by the National Nature Science Foundation of China (Nos. 81701208 and 81371371), Key Research and Development Plan of Zhejiang Province (No. 2019C03095), and Medicine and Health Technology Plan of Zhejiang Province (No. 2019KY396).



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Authors and Affiliations



YZ: project development, data collection and management, data analysis, manuscript writing. HJ: data collection and management, manuscript writing. YL: data collection and management, manuscript writing. YW: data collection and management. KX: data collection and management. LZ: data collection and management. HL: data collection and management. TS: data collection. DC: data management. JS: data collection and management. JZ: data management. DY: data management. DW: data management. RZ: project development, manuscript writing and editing.

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Correspondence to Renya Zhan.

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This study was approved by the Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine. Informed consent was obtained from study population or family members in all cases.

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Supplementary Figure 1

ROC curve analysis of serum ALP level for identifying patients with 6-month unfavorable outcome. The AUC was calculated based on the ROC curves and expressed as 95% CI. AUC ranges from 0.5 to 1.0. An AUC closer to 1 indicates a higher predictive power. (TIFF 100 kb)

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Zhu, Y., Jiang, H., Li, Y. et al. Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 31, 466–475 (2019).

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