Hematoma Expansion Following Intracerebral Hemorrhage: Mechanisms Targeting the Coagulation Cascade and Platelet Activation

Author(s): Sherrefa R. Burchell, Jiping Tang, John H. Zhang*

Journal Name: Current Drug Targets

Volume 18 , Issue 12 , 2017

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Graphical Abstract:


Hematoma expansion (HE), defined as a greater than 33% increase in intracerebral hemorrhage (ICH) volume within the first 24 hours, results in significant neurological deficits, and enhancement of ICH-induced primary and secondary brain injury. An escalation in the use of oral anticoagulants has led to a surge in the incidences of oral anticoagulation-associated ICH (OAT-ICH), which has been associated with a greater risk for HE and worse functional outcomes following ICH. The oral anticoagulants in use include vitamin K antagonists, and direct thrombin and factor Xa inhibitors. Fibrinolytic agents are also frequently administered. These all act via differing mechanisms and thus have varying degrees of impact on HE and ICH outcome. Additionally, antiplatelet medications have also been increasingly prescribed, and result in increased bleeding risks and worse outcomes after ICH. Aspirin, thienopyridines, and GPIIb/IIIa receptor blockers are some of the most common agents in use clinically, and also have different effects on ICH and hemorrhage growth, based on their mechanisms of action. Recent studies have found that reduced platelet activity may be more effective in predicting ICH risk, hemorrhage expansion, and outcomes, than antiplatelet agents, and activating platelets may thus be a novel target for ICH therapy. This review explores how dysfunctions or alterations in the coagulation and platelet cascades can lead to, and/or exacerbate, hematoma expansion following intracerebral hemorrhage, and describe the mechanisms behind these effects and the drugs that induce them. We also discuss potential future therapy aimed at increasing platelet activity after ICH.

Keywords: Hematoma expansion, intracerebral hemorrhage, anticoagulant, antiplatelet, oral-anticoagulant-associated ICH, Ctype lectin-like receptor 2, platelet activation.

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Article Details

Year: 2017
Published on: 24 August, 2017
Page: [1329 - 1344]
Pages: 16
DOI: 10.2174/1389450118666170329152305
Price: $65

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