Highlights
- •Clot retraction stabilizes thrombi by αIIbβ3-dependent interactions with fibrin and myosin-mediated contractile forces.
- •Activated platelets provide a surface for thrombin generation and are a source of proteins active in tissue repair.
- •Altered mechanosensitive properties of platelets within the clot influence thrombosis as in stroke and Covid-19 pathologies.
Abstract
Clot retraction is important for the prevention of bleeding, in the manifestations
of thrombosis and for tissue repair. The molecular mechanisms behind clot formation
are complex. Platelet involvement begins with adhesion at sites of vessel injury followed
by platelet aggregation, thrombin generation and fibrin production. Other blood cells
incorporate into a fibrin mesh that is consolidated by FXIIIa-mediated crosslinking
and platelet contractile activity. The latter results in the asymmetric redistribution
of erythrocytes into a tighter central mass providing the clot with stability and
resistance to fibrinolysis. Integrin αIIbβ3 on platelets is the key player in these
events, bridging fibrin and the platelet cytoskeleton. Glycoprotein VI participates
in thrombus formation but not in the retraction. Rheological and environmental factors
influence clot construction with retraction driven by the platelet cytoskeleton with
actomyosin acting as the motor. Activated platelets provide procoagulant activity
stimulating thrombin generation together with the release of a plethora of biologically
active proteins and substances from storage pools; many form chemotactic gradients
within the fibrin or the underlying matrix. Also released are newly synthesized metabolites
and lipid-rich vesicles that circulate within the vasculature and mimic platelet functions.
Platelets and their released elements play key roles in wound healing. This includes
promoting stem cell and mesenchymal stromal cell recruitment, fibroblast and endothelial
cell migration, angiogenesis and matrix formation. These properties have led to the
use of autologous clots in therapies designed to accelerate tissue repair while offering
the potential for genetic manipulation in both inherited and acquired diseases.
Keywords
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Article info
Publication history
Published online: August 18, 2022
Accepted:
August 10,
2022
Received in revised form:
August 8,
2022
Received:
June 6,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
