Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Khattar, Nicolas K; James, Robert F.

doi:10.3389/fneur.2018.00097

Cited by 17 publications

(13 citation statements)

References 44 publications

(52 reference statements)

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“…Heparin and low molecular weight heparin infusions have been evaluated in aSAH with inconsistent results . Heparin has antiinflammatory properties different than its role in anticoagulation.…”

Section: Resultsmentioning

confidence: 99%

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Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

et al. 2019

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Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies. Cerebral vasospasm continues to be a major source of clinical worsening in patients. We intended to review the clinical and experimental aspects of aSAH and identify strategies that are being evaluated for the treatment of vasospasm. A literature review on aSAH and cerebral vasospasm was performed. Available treatments for aSAH continue to expand as research continues to identify new therapeutic targets. Oral nimodipine is the primary medication used in practice given its neuroprotective properties. Transluminal balloon angioplasty is widely utilized in patients with symptomatic vasospasm and ischemia. Prophylactic “triple‐H” therapy, clazosentan, and intraarterial papaverine have fallen out of practice. Trials have not shown strong evidence supporting magnesium or statins. Other calcium channel blockers, milrinone, tirilazad, fasudil, cilostazol, albumin, eicosapentaenoic acid, erythropoietin, corticosteroids, minocycline, deferoxamine, intrathecal thrombolytics, need to be further investigated. Many of the current experimental drugs may have significant roles in the treatment algorithm, and further clinical trials are needed. There is growing evidence supporting that early brain injury in aSAH may lead to significant morbidity and mortality, and this needs to be explored further.

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Section: Resultsmentioning

confidence: 99%

“…Heparin and low molecular weight heparin infusions have been evaluated in aSAH with inconsistent results. [101][102][103] Heparin has antiinflammatory properties different than its role in anticoagulation. It is thought to attenuate the inflammatory response and restore bloodbrain barrier integrity.…”

Section: Heparin and Low Molecular Weight Heparinmentioning

confidence: 99%

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

et al. 2019

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“…However, its effect on cerebral edema in patients with aSAH has not been studied. 12 One mediator of microvascular constriction is endothelin-1 (ET-1). Heparin also can decrease the transcription of ET-1 and ET-1 promoters.…”

Section: Discussionmentioning

confidence: 99%

“…flammation, which are all the relevant mechanisms for the treatment of aSAH-induced brain injury. 11,12 Preclinical investigations in rodent models found that heparin reduced edema, neuroinflammation, demyelination, and transsynaptic neuronal apoptosis. 13 Because of the promising potential of heparin, we aimed to evaluate the latest evidence on the safety and efficacy of its usage in treating aSAH.…”

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confidence: 99%

Heparin in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Lukito

Lie

Helsa

et al. 2022

Neurosurgical Focus

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OBJECTIVE Cerebral vasospasm and the resulting infarction remain the most devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Limited treatment options are available, with nimodipine as the only approved prophylactic medication. In addition to its anticoagulant properties, heparin also has a pleiotropic and anti-inflammatory effect that could be beneficial in vasospasm. In this study, the authors sought to evaluate the efficacy and safety of heparin in the treatment of aSAH. METHODS The PubMed, EBSCOhost, Europe PMC, and Cochrane Central databases were searched to find studies including patients with aSAH who were treated with intravenous unfractionated heparin (UFH) after an aneurysm-securing procedure. Studies that did not include a comparison with UFH or low-molecular-weight heparin in deep vein thrombosis prophylactic doses were excluded. The primary outcome was cerebral vasospasm, and the secondary outcomes were cerebral infarction, clinical deterioration caused by delayed cerebral ischemia, bleeding complications, and thromboembolism complications. RESULTS Overall, 5 nonrandomized studies were included; 4 studies evaluated the safety and 3 studies evaluated the efficacy of intravenous heparin. From the analysis of 3 studies with a total of 895 patients, administration of intravenous UFH for > 48 hours was related to a significantly lower rate of cerebral infarction (OR 0.44, 95% CI 0.25–0.79). No significant association was found with other efficacy outcomes. Regarding cognitive outcome, one study found a significant improvement in Montreal Cognitive Assessment scores; however, the functional outcome as indicated by the modified Rankin Scale score was not improved by heparin administration. From the analysis of 4 studies with 1099 patients, no significant increases in bleeding and other complications were found. CONCLUSIONS Administration of intravenous UFH for more than 48 hours reduced the rate of cerebral infarction with a good safety profile. This result supports the ongoing clinical trial.

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“…Several studies have indicated the beneficial role of heparin. By using low dose heparin and its nanoparticles, it was observed that cognitive outcomes were better and the occurrence of vasospasm was reduced and cerebral ischemia was deferred for a brief period [66]. Nevertheless, advanced studies have proved that heparin has a diminutive effect on vasospastic damage, especially SAH-associated whereas it may still be effective in lowering inflammatory-related injuries that are related to SAH [67].…”

Section: Discussionmentioning

confidence: 99%

Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review

Ahmed

Khan

Kahlert

et al. 2021

IJMS

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Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.

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Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Cited by 17 publications

References 44 publications

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

Heparin in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review

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