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Review
. 2018 May;45(4):593-602.
doi: 10.1007/s11239-018-1641-2.

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

Diana A Gorog  1   2
Affiliations
Review

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

Diana A Gorog. J Thromb Thrombolysis. 2018 May.

Abstract

The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.

Keywords: Antithrombotic drugs; Endogenous fibrinolysis; Platelet aggregation; Thrombosis; Thrombus dispersion.

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Conflict of interest statement

Conflict of interest

The author reports no conflict of interest pertaining to this manuscript.

Research involving human and animal participants

This article does not contain any studies with human participants or animals.

Figures

Fig. 1
Fig. 1
Influences determining arterial thrombus stability, under high shear conditions. The strength of the attachment to the vessel wall and the tightness of the platelet core determine its ability to resist disruption by high shear forces and fibrinolysis. Medications that impact on thrombus stability are shown on left, NOAC non vitamin K oral anticoagulant
Fig. 2
Fig. 2
Key platelet and plasma proteins contributing to thrombus stability. I Platelet receptors and ligands involved in initial integrina IIbb3 activation and reversible platelet aggregation. The absence of these molecules increases thrombus instability. Also indicated is a box with intracellular signalling proteins controlling this process. II Contact-dependent signalling mechanisms implicated in platelet contraction and irreversible platelet aggregation. Fibrin formed by the coagulation process stabilizes the platelet aggregate. III Plasma coagulation factors, via the intrinsic (factor XII, FXII) and extrinsic (tissue factor, TF) pathways, mediating platelet-dependent thrombin and fibrin generation, stabilizing a growing thrombus. Also indicated is a primary mechanism of platelet-leucocyte interaction via P-selectin and PSGL-1. Reproduced with permission from Cosemans et al. [14]
See this image and copyright information in PMC

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