Thrombosis Mechanisms in Acute Ischemic Stroke

Acute ischaemic stroke arises when a thrombus obstructs a cerebral artery, depriving downstream tissue of oxygen and nutrients. Thrombus formation is initiated by endothelial injury or dysfunction, exposing subendothelial matrix and triggering platelet adhesion and activation. A cascade of coagulation factors generates thrombin, which converts fibrinogen into fibrin to stabilise the growing clot. Incorporation of red blood cells, white blood cells and platelets imparts mechanical heterogeneity, while platelet-driven contraction compacts the clot and expels serum. Local inflammation, mediated by neutrophils and neutrophil elastase, further remodels the thrombus and may promote fragmentation. Haemodynamic forces such as wall shear stress influence clot structure and susceptibility to fibrinolysis. Resistance to pharmacological or mechanical recanalisation often reflects thrombus composition, age and degree of contraction, with denser fibrin networks and higher granulocyte content associated with reduced treatment efficacy. An integrated understanding of these processes underpins the development of targeted therapies and optimisation of endovascular strategies.

Research from Nature Portfolio

Recent studies have revealed distinctive structural differences between arterial and venous thrombi and pulmonary emboli using high-resolution microscopy. All specimens contain tightly packed, non-biconcave red blood cells—so-called polyhedrocytes—indicating in vivo clot contraction. Arterial thrombi are rich in platelets and fibrin, whereas venous thrombi and emboli predominantly comprise contracted red blood cells and intermediate cellular forms. These origin-dependent microstructures affect clot stability, permeability and responsiveness to fibrinolytic agents. The reproducible differences in composition and architecture offer new insights into why arterial clots may resist standard reperfusion treatments more than venous-origin emboli, and suggest avenues for personalised therapeutic approaches.

Thrombosis Mechanisms in Acute Ischemic Stroke publication trend

The graph below shows the total number of articles in thrombosis mechanisms in acute ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Thrombus: A blood clot formed in situ within the vasculature, comprising platelets, fibrin and cellular elements.

Fibrinolysis: The enzymatic degradation of fibrin in a thrombus, primarily mediated by plasmin.

Clot contraction: The reduction in thrombus volume driven by activated platelets pulling on the fibrin network.

Polyhedrocytes: Densely packed, polygonal red blood cells created by clot contraction in vivo.

Shear stress: The tangential force exerted by flowing blood on the vessel wall or on a thrombus, influencing clot architecture and lysis.

References

1. Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes. Neurotherapeutics (2023).
2. Real‐time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in‐vitro thrombolysis model. Bioengineering & Translational Medicine (2023).
3. Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients Is Correlated with Stroke Subtype and Thrombus Attenuation. PLOS ONE (2014).
4. The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli. Scientific Reports (2020).