Coagulation
Physiology
Intrinsic / extrinsic / common pathway


Topic Completed: 1 June 2012

Minor changes: 9 March 2021

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PubMed Search: Common pathway [title] coagulation

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Cite this page: Parsons JC. Intrinsic / extrinsic / common pathway. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationcommonpathway.html. Accessed May 17th, 2021.
Common pathway
  • Involves fibrinogen (factor I), factors II (prothrombin), V, X
  • Thrombin converts soluble fibrinogen to insoluble fibrin
    • Releases fibrinopeptides A and B
  • Remaining fibrin monomers polymerize to form fibrin
  • Thrombin also binds to antithrombin, which inhibits thrombin to prevent excessive clotting
  • Thrombin may also activate factor XI (part of intrinsic pathway), factors V, VIII, XIII, XI and platelets
  • Factor XIII cross links fibrin to increase stability of fibrin clot
  • While both PT and aPTT include the common pathway, the PT is a more sensitive screening test for common pathway problems
  • References: Blomback: Essential Guide to Blood Coagulation, 1st Edition, 2010
Contact system
  • Consists of coagulation factors unknown in the 1950s
  • Includes factor XII (Hageman factor), prekallikrein (PK; Fletcher factor), high molecular weight kininogen (Williams, Flaujeac or Fitzgerald factor)
    • Some authors include factor XI
  • Made in the liver
  • Decreased activity is associated with liver disease, hepatic immaturity in newborns, antiphospholipid syndrome, Asian descent (for factor XII)
  • Homozygous deficiencies are rare, autosomal recessive
    • Cause very long PTT but no bleeding disorders and no definite association with hypercoagulability
  • Contact pathway may play a large role in inflammation, as patients with factor XI deficiency often have repeated infections
  • Recommended to not measure their activity in routine evaluation of patients with arterial or venous thromboembolism or acute coronary syndromes (Arch Pathol Lab Med 2002;126:1382)

Laboratory
  • Homozygous deficiencies cause prolonged PTT
  • Heterozygous deficiencies have near normal PTT
  • The test for a particular contact factor is based on the ability of the patient's plasma to correct a prolonged PTT in plasma that is deficient in the factor being tested
  • Even though the PTT may be decreased by deficiencies of contact factors, this does not necessarily correlate with increased bleeding risk
  • References: Kitchens: Consultative Hemostasis and Thrombosis, 2nd Edition, 2007
Extrinsic pathway
  • Involves tissue factor (TF), originally considered "extrinsic" to blood since it is present on cell surfaces not normally in contact with (i.e. extrinsic to) the circulatory system
  • The primary mechanism of the coagulation pathway in vivo is tissue factor binding to activated factor VII (factor VIIa)
  • TF-Factor VIIa complex activates factors X and IX (though in vivo it appears to first involve factors VIII and V from the intrinsic pathway, which then activate factors X and IX)
  • Activated factor IX activates more factor X, with cofactors activated factor VIII, anionic phospholipids (from activated platelets) and calcium
  • Activated factor X converts prothrombin to thrombin, with activated factor V, anionic phospholipids (from activated platelets) and calcium as cofactors
  • After initial activation, pathway is inhibited by the binding of tissue factor pathway inhibitor (TFPI) to factor Xa, which inhibits TF-Factor VIIa complex, and further coagulation is dependent on the intrinsic pathway
  • Merges with extrinsic pathway into common pathway
  • The prothrombin time (PT) measures the extrinsic and common pathways
  • References: Kolde: Haemostasis: Physiology, Pathology, Diagnostics, Limited Edition, 2004
Intrinsic pathway
  • Involves factors VIII, IX, XI, XII (Hageman factor), prekallikrein, high molecular weight kininogen (Wikipedia - Coagulation)
  • Merges with extrinsic pathway into common pathway
  • Activated when factor XII binds to negatively charged "foreign" surface exposed to blood
  • Then sequentially activates factors XI, IX, X, then factor II (prothrombin to thrombin), which converts fibrinogen to fibrin (see common pathway)
  • Once extrinsic pathway is inhibited by TFPI-Xa complex (see extrinsic pathway), factor VIIIa / IXa complex becomes dominant generator of factor Xa, thrombin and fibrin
  • Factor XIIa also converts prekallikrein to kallikrein, which activates more factor XIIa
    • Both require high molecular weight kininogen as cofactors
  • Kallikrein also releases bradykinin from high molecular weight kininogen, which causes vasoconstriction
  • The activated partial thromboplastin time (aPTT) measures the intrinsic and common pathways
  • References: Kolde: Haemostasis: Physiology, Pathology, Diagnostics, Limited Edition, 2004
Diagrams / tables

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Coagulation

Extrinsic pathway

Intrinsic pathway

Intrinsic, common and extrinsic pathways

In vivo coagulation cascade

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