How it all starts: Initiation of the clotting cascade

Stephanie A. Smith, Richard J. Travers, James H. Morrissey

Research output: Contribution to journalReview article

Abstract

The plasma coagulation system in mammalian blood consists of a cascade of enzyme activation events in which serine proteases activate the proteins (proenzymes and procofactors) in the next step of the cascade via limited proteolysis. The ultimate outcome is the polymerization of fibrin and the activation of platelets, leading to a blood clot. This process is protective, as it prevents excessive blood loss following injury (normal hemostasis). Unfortunately, the blood clotting system can also lead to unwanted blood clots inside blood vessels (pathologic thrombosis), which is a leading cause of disability and death in the developed world. There are two main mechanisms for triggering the blood clotting, termed the tissue factor pathway and the contact pathway. Only one of these pathways (the tissue factor pathway) functions in normal hemostasis. Both pathways, however, are thought to contribute to thrombosis. An emerging concept is that the contact pathway functions in host pathogen defenses. This review focuses on how the initiation phase of the blood clotting cascade is regulated in both pathways, with a discussion of the contributions of these pathways to hemostasis versus thrombosis.

Original languageEnglish (US)
Pages (from-to)326-336
Number of pages11
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume50
Issue number4
DOIs
StatePublished - Jul 4 2015

Fingerprint

Thrombosis
Blood
Blood Coagulation
Hemostasis
Thromboplastin
Enzyme Precursors
Enzyme Activation
Platelet Activation
Serine Proteases
Chemical activation
Fibrin
Proteolysis
Polymerization
Blood Vessels
Cause of Death
Blood vessels
Pathogens
Platelets
Coagulation
Wounds and Injuries

Keywords

  • Blood coagulation
  • contact pathway
  • factor VII
  • factor XII
  • polyphosphate
  • tissue factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

How it all starts : Initiation of the clotting cascade. / Smith, Stephanie A.; Travers, Richard J.; Morrissey, James H.

In: Critical Reviews in Biochemistry and Molecular Biology, Vol. 50, No. 4, 04.07.2015, p. 326-336.

Research output: Contribution to journalReview article

Smith, Stephanie A. ; Travers, Richard J. ; Morrissey, James H. / How it all starts : Initiation of the clotting cascade. In: Critical Reviews in Biochemistry and Molecular Biology. 2015 ; Vol. 50, No. 4. pp. 326-336.
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