Coagulation
Physiology
Intrinsic / extrinsic / common pathway
Author: Jeremy C. Parsons, M.D.
Topic Completed: 1 June 2012
Minor changes: 30 August 2021
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: Common pathway [title] coagulation
Table of Contents
Common pathway | Contact system | Extrinsic pathway | Intrinsic pathway | Diagrams / tablesCite this page: Parsons JC. Intrinsic / extrinsic / common pathway. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationcommonpathway.html. Accessed January 21st, 2022.
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
- Prothrombin factor 1.2 is released (see common pathway)
- 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
Images hosted on other servers:
Coagulation
Extrinsic pathway
Intrinsic pathway
Intrinsic, common and extrinsic pathways
In vivo coagulation cascade
