Skip to main content
SpringerLink
Log in
Book cover

Subarachnoid Hemorrhage pp 15–19Cite as

Heparin Treatment in Aneurysmal Subarachnoid Hemorrhage: A Review of Human Studies

  • Chapter
  • First Online:

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 127))

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of stroke disability despite gradual reductions in physical morbidity and mortality. Heparin is an effective anti-inflammatory agent and may potentially prevent delayed neurological injury in the days to weeks after the hemorrhage. Various human studies have shown the safety of a continuous infusion of low-dose unfractionated heparin in the setting of subarachnoid hemorrhage as well as its efficacy in minimizing delayed neurological deficits including symptomatic cerebral vasospasm, vasospasm-related infarction, and cognitive dysfunction. Studies have also shown mixed results with low-molecular-weight heparin usage in this patient population. Heparin treatment is not associated with significant hemorrhagic complications; however, vigilance is essential for early detection of heparin-induced thrombocytopenia in order to prevent devastating sequelae. Multicenter randomized controlled trials are necessary for objective characterization of the effects of heparin.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010;41:e519–36.

    Article  Google Scholar 

  2. Bruder M, Won S-YY, Kashefiolasl S, Wagner M, Brawanski N, Dinc N, Seifert V, Konczalla J. Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional ‘H’ therapy in vasospasm treatment. J Neurointerv Surg. 2017;9:659–63.

    Article  Google Scholar 

  3. Crowley MG, Liska MG, Borlongan CV. Stem cell therapy for sequestering neuroinflammation in traumatic brain injury: an update on exosome-targeting to the spleen. J Neurosurg Sci. 2017;61:291–302.

    PubMed  Google Scholar 

  4. Girolami B, Prandoni P, Stefani PM, Tanduo C, Sabbion P, Eichler P, Ramon R, Baggio G, Fabris F, Girolami A. The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood. 2003;101:2955–9.

    Article  CAS  Google Scholar 

  5. Hacker RI, Ritter G, Nelson C, Knobel D, Gupta R, Hopkins K, Marini CP, Barrera R. Subcutaneous heparin does not increase postoperative complications in neurosurgical patients: an institutional experience. J Crit Care. 2012;27:250–4.

    Article  CAS  Google Scholar 

  6. Harbrecht U, Bastians B, Kredteck A, Hanfland P, Klockgether T, Pohl C. Heparin-induced thrombocytopenia in neurologic disease treated with unfractionated heparin. Neurology. 2004;62:657–9.

    Article  CAS  Google Scholar 

  7. Hellawell DJ, Taylor R, Pentland B. Persisting symptoms and carers’ views of outcome after subarachnoid haemorrhage. Clin Rehabil. 1999;13:333–40.

    Article  CAS  Google Scholar 

  8. James RF, Khattar NK, Aljuboori ZS, Page P, Shao EY, Carter LM, Meyer KS, Daniels MJ, Craycroft J, Gaughen JR Jr, Chaudry MI, Rai SN, Everhart DE, Simard JM. Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes. J Neurosurg. 2018;11:1–8. https://doi.org/10.317.1/2017.11.JNS17894 [Epub ahead of print].

  9. Kreiter KT, Copeland D, Bernardini GL, Bates JE, Peery S, Claassen J, Du YE, Stern Y, Connolly ES, Mayer SA. Predictors of cognitive dysfunction after subarachnoid hemorrhage. Stroke. 2002;33:200–8.

    Article  Google Scholar 

  10. Manoel AL, Turkel-Parrella D, Germans M, Kouzmina E, Almendra Pda S, Marotta T, Spears J, Abrahamson S. Safety of early pharmacological thromboprophylaxis after subarachnoid hemorrhage. Can J Neurol Sci. 2014;41:554–61.

    Article  Google Scholar 

  11. Mavaddat N, Sahakian BJ, Hutchinson PJ, Kirkpatrick PJ. Cognition following subarachnoid hemorrhage from anterior communicating artery aneurysm: relation to timing of surgery. J Neurosurg. 1999;91:402–7.

    Article  CAS  Google Scholar 

  12. Parra A, Kreiter KT, Williams S, Sciacca R, Mack WJ, Naidech AM, Commichau CS, Fitzsimmons BF, Janjua N, Mayer SA, Connolly ES Jr. Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study. Neurosurgery. 2005;56:476–84; discussion 476–84.

    Article  Google Scholar 

  13. Provencio JJ, Vora N. Subarachnoid hemorrhage and inflammation: bench to bedside and back. Semin Neurol. 2005;25:435–44.

    Article  Google Scholar 

  14. Pyne-Geithman GJ, Caudell DN, Prakash P, Clark JF. Glutathione peroxidase and subarachnoid hemorrhage: implications for the role of oxidative stress in cerebral vasospasm. Neurol Res. 2009;31:195–9.

    Article  CAS  Google Scholar 

  15. Siironen J, Juvela S, Varis J, Porras M, Poussa K, Ilveskero S, Hernesniemi J, Lassila R. No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled clinical trial. J Neurosurg. 2003;99:953–9.

    Article  CAS  Google Scholar 

  16. Simard JM, Aldrich EF, Schreibman D, James RF, Polifka A, Beaty N. Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment. J Neurosurg. 2013;119:1611–9.

    Article  Google Scholar 

  17. Simard JM, Schreibman D, Aldrich EF, Stallmeyer B, Le B, James RF, Beaty N. Unfractionated heparin: multitargeted therapy for delayed neurological deficits induced by subarachnoid hemorrhage. Neurocrit Care. 2010;13:439–49.

    Article  CAS  Google Scholar 

  18. Simard JM, Tosun C, Ivanova S, Kurland DB, Hong C, Radecki L, Gisriel C, Mehta R, Schreibman D, Gerzanich V. Heparin reduces neuroinflammation and transsynaptic neuronal apoptosis in a model of subarachnoid hemorrhage. Transl Stroke Res. 2012;3:155–65.

    Article  CAS  Google Scholar 

  19. Stein SC, Levine JM, Nagpal S, LeRoux PD. Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence? Neurosurg Focus. 2006;21:E2.

    Article  Google Scholar 

  20. Vergouwen MD, Vermeulen M, Coert BA, Stroes ES, Roos YB. Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1761–70.

    Article  Google Scholar 

  21. Wessell A, Kole MJ, Badjatia N, Parikh G, Albrecht JS, Schreibman DL, Simard JM. High compliance with scheduled nimodipine is associated with better outcome in aneurysmal subarachnoid hemorrhage patients cotreated with heparin infusion. Front Neurol. 2017;8:268.

    Article  Google Scholar 

  22. Wurm G, Tomancok B, Nussbaumer K, Adelwohrer C, Holl K. Reduction of ischemic sequelae following spontaneous subarachnoid hemorrhage: a double-blind, randomized comparison of enoxaparin versus placebo. Clin Neurol Neurosurg. 2004;106:97–103.

    Article  Google Scholar 

  23. Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122:743–52.

    Article  CAS  Google Scholar 

  24. Zachariah J, Snyder KA, Graffeo CS, Khanal DR, Lanzino G, Wijdicks EF, Rabinstein AA. Risk of ventriculostomy-associated hemorrhage in patients with aneurysmal subarachnoid hemorrhage treated with anticoagulant thromboprophylaxis. Neurocrit Care. 2016;25:224–9.

    Article  CAS  Google Scholar 

  25. Zhang ZD, Macdonald RL. Contribution of the remodeling response to cerebral vasospasm. Neurol Res. 2006;28:713–20.

    Article  Google Scholar 

Download references

Conflict of Interest

RFJ is the study chair for ASTROH, a phase 2 clinical trial evaluating heparin treatment in aneurysmal subarachnoid hemorrhage. We delare that we have no other conflicts of interest with the contents of this manuscript.

Source of Funding: None.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, KY, USA

    Nicolas K. Khattar, Esther Bak & Robert F. James

  2. Department of Radiology, School of Medicine, University of Louisville, Louisville, KY, USA

    Andrew C. White

Authors
  1. Nicolas K. Khattar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esther Bak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew C. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert F. James
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert F. James .

Editor information

Editors and Affiliations

  1. Department of Anethesiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    Robert D. Martin

  2. Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA, USA

    Warren Boling

  3. Department of Neurosurgery, First Affiliated Hospital of Soochow University, Suzhou, China

    Gang Chen

  4. Department of Anesthesiology and Physiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    John H. Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khattar, N.K., Bak, E., White, A.C., James, R.F. (2020). Heparin Treatment in Aneurysmal Subarachnoid Hemorrhage: A Review of Human Studies. In: Martin, R., Boling, W., Chen, G., Zhang, J. (eds) Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 127. Springer, Cham. https://doi.org/10.1007/978-3-030-04615-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-04615-6_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-04614-9

  • Online ISBN: 978-3-030-04615-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation