Reduction of perioperative rebleeding in aneurysmal subarachnoid hemorrhage with combination therapy of hemocoagulase and antifibrinolytics: A multicenter retrospective study

Abstract

Background: Rebleeding following aneurysmal subarachnoid hemorrhage (aSAH) interventions significantly increases mortality and disability. While hemostatic agents are commonly used to prevent rebleeding, the efficacy of antifibrinolytics as monotherapy remains controversial, and thrombins has limited supporting evidence. This study investigates the impact of hemocoagulase, a thrombin-like agent, and its combination with antifibrinolytics on reducing rebleeding and improving functional outcomes in aSAH patients undergoing invasive treatments, providing insights into optimal medication strategies for aSAH management. Methods: We conducted a retrospective analysis of data from aSAH patients across three medical institutions over a ten-year period. We compared post-treatment outcomes and the incidence of adverse events between two cohorts those who received hemocoagulase and antifibrinolytics during the perioperative period and those who did not. Primary outcomes included mortality, dependency in activities of daily living, and length of stay. Secondary outcomes comprised rebleeding and cerebral ischemic incidents. Results: The study included 345 aSAH patients who underwent neurosurgical interventions, with 81.16% receiving hemostatic agents. Patients treated with hemostatic medications exhibited a significantly lower incidence of hemiplegia compared to the control cohort. However, no differences were observed in rebleeding or cerebral ischemic events. Notably, for patients who received a combination of hemocoagulase and a single antifibrinolytic agent, the incidence of rebleeding within 72 hours post-intervention and overall postoperative rebleeding was significantly lower. Conclusion: The use of hemostatic agents during the perioperative period of aSAH may improve functional outcomes. Combining hemocoagulase with a single antifibrinolytic agent appears to reduces early rebleeding following aSAH interventions.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research was funded by CHANGZHOU SIYAO Hospital Pharmacy Research Fund, Nanjing Pharmaceutical Association (2022YX011) and Nanjing Health Science and Technology Development Special Fund, Nanjing Health Commission (YKK23118).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committees of Nanjing First hospital, Nanjing Medical University [KY20230424-01-KS-01], The Second Affiliated Hospital of Nanjing Medical University [2023-KY-147-01], and Sir Run Run Hospital, Nanjing Medical University [2023-SR-020] gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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