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Unfractionated Heparin: Multitargeted Therapy for Delayed Neurological Deficits Induced by Subarachnoid Hemorrhage

Neurocritical Care volume 13, pages 439–449 (2010)Cite this article

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is associated with numerous “delayed neurological deficits” (DNDs) that have been attributed to multiple pathophysiological mechanisms, including ischemia, microthrombosis, free radical damage, inflammation, and vascular remodeling. To date, effective prophylactic therapy for SAH-induced DNDs has been elusive, due perhaps to the multiplicity of mechanisms involved that render typical, single-agent therapy seemingly futile. We hypothesized that heparin, which has multiple underappreciated salutary effects, might be useful as a multitargeted prophylactic agent against SAH-induced DNDs. We performed a comprehensive review of the literature to evaluate the potential utility of heparin in targeting the multiple pathophysiological mechanisms that have been identified as contributing to SAH-induced DNDs. Our literature review revealed that unfractionated heparin can potentially antagonize essentially all of the pathophysiological mechanisms known to be activated following SAH. Heparin binds >100 proteins, including plasma proteins, proteins released from platelets, cytokines, and chemokines. Also, heparin complexes with oxyhemoglobin, blocks the activity of free radicals including reactive oxygen species, antagonizes endothelin-mediated vasoconstriction, smooth muscle depolarization, and inflammatory, growth and fibrogenic responses. Our review suggests that the use of prophylactic heparin following SAH may warrant formal study.

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Acknowledgments

JMS is supported by grants from the National Institutes of Health (HL082517, NS061808, NS060801), the Department of Veterans Affairs (Baltimore VA), the Department of Defense (PT074766, SC090293), and the Christopher and Dana Reeves Foundation.

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Author notes

  1. Robert F. James

    Present address: Department of Surgery (Neurosurgery), East Carolina University, Greenville, NC, 27858, USA

Authors and Affiliations

  1. Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA

    J. Marc Simard, E. Francois Aldrich, Robert F. James & Narlin Beaty

  2. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    J. Marc Simard

  3. Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    J. Marc Simard

  4. Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    David Schreibman & Brian Le

  5. Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Bernadette Stallmeyer

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  1. J. Marc Simard
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Correspondence to J. Marc Simard.

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Simard, J.M., Schreibman, D., Aldrich, E.F. et al. Unfractionated Heparin: Multitargeted Therapy for Delayed Neurological Deficits Induced by Subarachnoid Hemorrhage. Neurocrit Care 13, 439–449 (2010). https://doi.org/10.1007/s12028-010-9435-1

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Keywords

  • Subarachnoid hemorrhage
  • Vasospasm
  • Inflammation
  • Heparin