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Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis.

Julian V ClarkeJulia M SuggsDeepti DiwanJin Vivian LeeKim LipseyAnanth K VellimanaGregory J Zipfel
Published in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2020)
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following SAH, as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process. Upon review of the literature, we discovered that microvascular platelet aggregation and thrombosis occur after experimental SAH across multiple species and SAH induction techniques in a similar time frame to other components of DCI, occurring in the cerebral cortex and hippocampus across both hemispheres. We discuss the relationship of these findings to human autopsy studies. In the final section of this review, we highlight the important therapeutic options for targeting microvascular platelet aggregation and thrombosis, and emphasize why therapeutic targeting of this neurovascular pathology may improve patient care. We encourage ongoing research into the pathophysiology of SAH and DCI, especially in regard to microvascular platelet aggregation and thrombosis and the translation to randomized clinical trials.
Keyphrases
  • subarachnoid hemorrhage
  • cerebral ischemia
  • pulmonary embolism
  • brain injury
  • endothelial cells
  • clinical trial
  • blood brain barrier
  • case control
  • pluripotent stem cells
  • study protocol
  • phase iii