Defects of platelet signal transduction

Binggang Xiang, Zhenyu Li

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Blood platelets play an essential role in hemostasis. The primary physiological function of platelets is to form hemostatic thrombi that prevent blood loss and maintain vascular integrity, which requires a robust and precise response of platelets to vascular injury. On the other hand, platelet activation must be tightly controlled. Dysregulated thrombus formation (thrombosis) causes blockage of blood vessels, leading to ischemia. Platelets in normal circulation are in a non-adherent "resting" state. Upon vascular injury, platelets are activated following initial adhesion to adhesive proteins like von Willebrand factor (VWF) and collagen or by soluble platelet agonists like ADP, thrombin, and thromboxane A2 (TXA2). These adhesive proteins and soluble agonists induce signal transduction via their respective receptors and receptor-specific signaling pathways. The various receptorspecific platelet activation signaling pathways converge into common signaling events, such as activation of PKC and Ca2+ mobilization, which stimulate platelet shape change, granule secretion, and ultimately induce the "inside-out" signaling process leading to activation of the ligand binding function of integrin αIIbβ3. Ligand binding to integrin αIIbβ3 mediates platelet adhesion and aggregation and triggers "outside-in" signaling, resulting in platelet spreading, granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction. Defects in platelet signal transduction may lead to bleeding disorder. This chapter briefly introduces normal signal transduction of platelet activation followed by detailed description of inherited defects in the signaling molecules in platelets including receptors and kinases, leading to impaired platelet function and bleeding disorders (Table 1).

Original languageEnglish
Title of host publicationPlatelets in Thrombotic and Non-Thrombotic Disorders
Subtitle of host publicationPathophysiology, Pharmacology and Therapeutics: an Update
Number of pages14
ISBN (Electronic)9783319474625
StatePublished - Mar 8 2017

Bibliographical note

Publisher Copyright:
© Springer International Publishing AG 2017.

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine


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