Platelet response heterogeneity in thrombus formation.

  title={Platelet response heterogeneity in thrombus formation.},
  author={Imke C. A. Munnix and Judith M.E.M. Cosemans and Jocelyn M. Auger and Johan W. M. Heemskerk},
  journal={Thrombosis and haemostasis},
  volume={102 6},
Vascular injury leads to formation of a structured thrombus as a consequence of platelet activation and aggregation, thrombin and fibrin formation, and trapping of leukocytes and red cells. This review summarises current evidence for heterogeneity of platelet responses and functions in the thrombus-forming process. Environmental factors contribute to response heterogeneity, as the platelets in a thrombus adhere to different substrates, and sense specific (ant)agonists and rheological conditions… 

Figures and Tables from this paper

Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, and activation

It is shown for the first time that platelets sense the stiffness of the underlying clot substrate, and increasing substrate stiffness increases platelet adhesion and spreading, and provides biophysical insight into the underlying mechanisms of platelet aggregation and platelet activation heterogeneity during thrombus formation.

Insights into platelet-based control of coagulation.

Platelet interaction with activated endothelium: mechanistic insights from microfluidics.

This review provides insight into the platelet-endothelial interface, based on in vitro flow chamber studies and cross referenced with in vivo thrombosis studies, and offers recommendations for setting up, reporting, interpreting, and comparing endothelial-lined flow chamber Studies.

Platelet‐based coagulation: different populations, different functions

It is postulate that different populations of platelets with distinct surface properties are involved in these coagulant functions of blood coagulation.

Procoagulant platelets: Generation, characteristics, and therapeutic target

This review summarizes the generation and important characteristics of procoagulant platelets, as well as their potential for preventing the adverse effects associated with current antiplatelet therapies.

Platelets and Coagulation

This chapter describes the roles of platelets in detail, also focusing on the receptors and signaling pathways involved and on the distinct (anti)coagulant pathways.

Platelets and Fibrinolysis

This chapter outlines current knowledge on the complex cross-talk between platelets and fibrinolysis and its implications for physiological and pathological hemostasis.

No Escape-A Novel Tool to Quantify Platelet Intra-Thrombus Movements.

A new computational tool which enables quantitative analysis of platelet intra-thrombus movements is introduced and a big set of data supports and conclusively explains the spatial and functional heterogeneity of a thrombus.



Segregation of Platelet Aggregatory and Procoagulant Microdomains in Thrombus Formation: Regulation by Transient Integrin Activation

The hemostatic activity of a developing thrombus is determined by the balance in formation of proaggregatory and procoagulant platelets, which is influenced by antiplatelet and anticoagULant medication.

Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation.

A new mechanism initiating platelet aggregation that is critically influenced by shear, physical proximity between translocating platelets, and membrane tether formation is identified and a model to explain how the discoid morphology of platelets facilitates the maintenance of adhesive interactions with thrombogenic surfaces under high shear stress conditions is provided.

The growing complexity of platelet aggregation.

The identification of shear-dependent mechanisms of platelet aggregation has raised the possibility that vascular-bed-specific inhibitors of platelets aggregation may be developed in the future that are safer and more effective than existing antiplatelet agents.

Conversion of platelets from a proaggregatory to a proinflammatory adhesive phenotype: role of PAF in spatially regulating neutrophil adhesion and spreading.

A differential role for platelets in supporting platelet and neutrophil adhesive interactions under flow is demonstrated and a specific proinflammatory function for annexin A5+ve platelets is defined, which plays an important role in localizing neutrophils on the surface of thrombi.

Complementary roles of platelet glycoprotein VI and integrin α2β1 in collagen‐induced thrombus formation in flowing whole blood ex vivo

Data indicate that integrin α2β1 facilitates the central function of GPVI in the platelet activation processes that lead to thrombus formation, whereas the autocrine thromboxane A2 and ADP serve mainly to trigger aggregate formation.

Platelet activation and blood coagulation.

Platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis and platelets take over the initiating role of tissue factor and factor VIIa in coagulations activation.

Platelet adhesion signalling and the regulation of thrombus formation

  • J. Gibbins
  • Biology, Medicine
    Journal of Cell Science
  • 2004
Understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis and adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelets function and thrombus formation in the healthy circulation.

Platelets and thrombin generation.

Examination of evidence that platelets play a major role in localizing and controlling the burst of thrombin generation leading to fibrin clot formation concludes that changes in lipid composition are necessary but not sufficient to account for platelet surface regulation of thROMbin generation.

Platelet Factor XIII and Calpain Negatively Regulate Integrin αIIbβ3 Adhesive Function and Thrombus Growth*

These studies define a previously unidentified role for platelet FXIII and calpain in regulating integrin αIIbβ3 adhesive function and demonstrate the existence of an autoregulatory feedback mechanism that serves to limit excessive platelet accumulation on highly reactive thrombogenic surfaces.