Microthrombosis after Aneurysmal Subarachnoid Hemorrhage: An Additional Explanation for Delayed Cerebral Ischemia

Abstract

Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral ischemia is considered to be caused by vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not successful in preventing ischemia. The purpose of this review is to give an overview of clinical data showing that DCI cannot always be attributed to vasospasm, and to present an in-depth analysis of clinical and autopsy studies on the role of microthrombosis in the pathogenesis of DCI. Clinical studies show that DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, impaired fibrinolytic activity, and inflammatory and endotheliumrelated processes, lead to the formation of microthrombi, which ultimately result in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in the pathophysiology of DCI is crucial for the development of effective therapies against this complication. Because multiple pathways are involved, future research should focus on drugs with pleiotropic effects.

Pharmacologic Reduction of Angiographic Vasospasm in Experimental Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis

“…Most models of SAH differ from human SAH in that animals do not develop cerebral infarctions or other delayed processes that are proposed to be important in humans, such as cortical spreading ischemia and microthromboembolism (Dreier et al, 2009;Vergouwen et al, 2008). The end points in human clinical trials are usually clinical outcome and delayed cerebral ischemia but neurological and functional examination after experimental SAH is still uncommonly used (Jeon et al, 2009;Takata et al, 2008).…”

Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca 2+ -activated K + (BK) channels

“…Additional mechanisms that may contribute to SAH-induced DINDs include early brain injury, inflammation, cortical spreading depression, and focal cortical infarcts arising from perfusion deficiencies within the microcirculation (5,6,10,11). Perfusion deficiencies reflecting restricted blood flow through intracerebral (parenchymal) arterioles could result from microthrombi formation (12), vasoconstriction caused by extravascular blood or blood breakdown products (13,14), or impaired neurovascular coupling (15).…”

The Impact of Nonsteroidal Anti-inflammatory Drugs on Inflammatory Response After Aneurysmal Subarachnoid Hemorrhage

“…In theory, the potential inhibitory effect of NSAIDs on platelet aggregation might act beneficial too as activation of the coagulation cascade and occurrence of microthrombosis has been discussed to contribute to the pathogenesis of cerebral infarction [34]. Clinical studies with antiplatelet therapies showed a trend towards improved outcome.…”