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 Platelets

General considerations

  • Platelet production and structure.
  • Platelet kinetics and life span.
  • Platelet membrane glycoproteins.

The role of platelets in vascular disease

  • Adhesion.
  • Aggregation.
  • Secretion, including dense bodies, alpha granules, platelet specific proteins (platelet factor 4, β -thromboglobulin, platelet-derived growth factor and thrombospondin).
  • Inhibition of secretion.

Biochemistry of platelet activation and inhibition

  • The importance of thromboxane.
  • Other agonists of platelet activation (including thrombin, collagen, ADP, epinephrine, platelet activating factor and ristocetin).
  • Platelet inhibitors (including aspirin, indomethacin and sulindac, phenylbutazone and sulfinpyrazone, nonsteroidal anti-inflammatory drugs, dipyridamole, prostacyclin, thromboxane synthetase inhibitors, thromboxane receptor antagonists, ticlopidine and glycoprotein IIb-IIIa inhibitors).

Platelet interactions with coagulant proteins

  • Coagulation proteins in platelets (including fibrinogen, factor V, von Willebrand factor, high-molecular weight kininogen, factor XI, factor XIII and plasma protease inhibitors).
  • Platelet contribution to the coagulation mechanism (including contact activation and factor X).

References

Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets 2001;12:261-273.

Although anucleated, blood platelets are highly organized cells rich in different types of organelles. Dense granules contain small non-protein molecules that are secreted to recruit other platelets. alpha-Granules contain large adhesive and healing proteins. Lysosomes contain hydrolases able to eliminate the circulating platelet aggregate. Granules' constituents, secretion and functions as well as typical platelet disorders resulting from a storage granule abnormality are described in this review article.

Savage B, Cattaneo M, Ruggeri ZM. Mechanisms of platelet aggregation. Curr Opin Hematol 2001;8:270-276.

This review focuses on recent developments in elucidating the mechanisms that regulate platelet aggregation. The role of platelet receptors for collagen, von Willebrand factor, thrombin and adenosine diphosphate is briefly reviewed.

Sachais BS. Platelet-endothelial interactions in atherosclerosis. Curr Atheroscler Rep 2001;3:412-416.

This article reviews recent evidence showing how the interaction between platelets and endothelial cells may play a important role in the pathogenesis of atherosclerosis, suggesting an underappreciated potential locus for pharmacologic intervention.

Bennett JS. Novel platelet inhibitors. Annu Rev Med. 2001;52:161-84.

This review addresses our current understanding of platelet function and how this information has been applied to the discovery of novel platelet inhibitors. Platelet inhibitors include inhibitors of prostaglandin-stimulated platelet activation, inhibitors of ADP-mediated platelet activation, phosphodiesterase inhibitors, inhibitors under development (CD39/ATP diphosphohydrolase and thrombin receptor inhibitors) and antagonists of ligand binding to α IIbß3. The evidence on the efficacy of each platelet inhibitor is summarized.

Ofosu FA. The blood platelet as a model for regulating blood coagulation on cell surfaces and its consequences. Biochemistry (Mosc) 2002;67:47-55.

This review is divided into three sections. The first section considers the contributions of platelet-derived and plasma-derived reactants to prothrombin activation on platelets. The second section briefly reviews the mechanisms of platelet activation and the critical role of platelet activation in hemostasis. The third section reviews some of the pathological consequences that can arise from inadequate regulation of platelet activation.

Posted June 2010