Contact activation system: Difference between revisions

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'''Contact Activation System''' (CAS) is a critical component of the [[Innate Immune System|innate immune system]] and the [[Coagulation|coagulation cascade]], playing a pivotal role in [[Inflammation|inflammation]], [[Blood Coagulation|blood coagulation]], and [[Wound Healing|wound healing]]. The system is initiated when blood comes into contact with negatively charged surfaces, leading to a series of enzymatic reactions that ultimately result in blood clot formation and activation of inflammatory pathways.
{{Short description|Overview of the contact activation system in the coagulation cascade}}


==Overview==
== Contact Activation System ==
The contact activation system is initiated through the activation of [[Factor XII (Hageman factor)|Factor XII]] (Hageman factor), a plasma protein. Upon encountering negatively charged surfaces, such as those presented by [[Bacterial Cell Walls|bacterial cell walls]], damaged tissue, or artificial surfaces like those found in medical devices, Factor XII undergoes a conformational change and becomes activated (Factor XIIa). This activation marks the start of a cascade involving several other components, including prekallikrein (PK) and high molecular weight kininogen (HK), leading to further activation of the coagulation cascade and the generation of [[Bradykinin|bradykinin]], a potent vasodilator involved in inflammatory responses.
The '''contact activation system''' is a crucial component of the [[coagulation cascade]], which is responsible for initiating the [[intrinsic pathway]] of blood coagulation. This system is activated when blood comes into contact with negatively charged surfaces, such as glass or collagen, leading to a series of enzymatic reactions that ultimately result in the formation of a blood clot.


==Components==
[[File:Contact system.svg|thumb|right|Diagram of the contact activation system]]
The contact activation system consists of the following key components:
* '''[[Factor XII (Hageman factor)|Factor XII]]''': Initiates the cascade upon activation.
* '''[[Prekallikrein (PK)|Prekallikrein (PK)]]''': Activated by Factor XIIa to kallikrein, which in turn can further activate Factor XII and cleave HK to release bradykinin.
* '''[[High Molecular Weight Kininogen (HK)|High Molecular Weight Kininogen (HK)]]''': Serves as a cofactor for the activation of prekallikrein and the generation of bradykinin.


==Pathway==
=== Components ===
The activation pathway of the contact system can be summarized as follows:
The contact activation system involves several key proteins and enzymes, including:
1. Activation of Factor XII to Factor XIIa upon contact with negatively charged surfaces.
2. Factor XIIa activates prekallikrein to kallikrein.
3. Kallikrein activates more Factor XII, amplifying the response, and cleaves HK to release bradykinin.
4. Bradykinin promotes inflammation, increases vascular permeability, and induces pain.


Additionally, Factor XIIa can initiate the intrinsic pathway of the coagulation cascade by converting [[Factor XI]] to Factor XIa, further promoting clot formation.
* '''[[Factor XII]]''' (Hageman factor): This is the first protein to be activated in the contact system. It is converted to its active form, Factor XIIa, upon contact with a negatively charged surface.
* '''[[Prekallikrein]]''': This is converted to kallikrein by Factor XIIa. Kallikrein further activates Factor XII, creating a positive feedback loop.
* '''[[High-molecular-weight kininogen]]''' (HMWK): This acts as a cofactor, enhancing the activation of Factor XII and prekallikrein.
* '''[[Factor XI]]''': Activated by Factor XIIa, it plays a role in the downstream activation of the intrinsic pathway.


==Clinical Significance==
=== Mechanism ===
The contact activation system has been implicated in various clinical conditions, including [[Hereditary Angioedema|hereditary angioedema]], due to excessive bradykinin production, and in the development of thrombosis associated with artificial surfaces used in medical devices. Inhibitors of the contact system components, particularly targeting Factor XIIa, are under investigation for their potential therapeutic benefits in preventing thrombosis without increasing bleeding risk, offering a promising avenue for anticoagulant therapy.
The activation of the contact system begins when Factor XII binds to a negatively charged surface. This binding induces a conformational change in Factor XII, allowing it to autoactivate to Factor XIIa. Factor XIIa then activates prekallikrein to kallikrein, which in turn further activates more Factor XII, amplifying the response.


==Research Directions==
Kallikrein also cleaves HMWK to release [[bradykinin]], a peptide that increases vascular permeability and contributes to inflammation. Factor XIIa activates Factor XI, which then activates Factor IX, leading to the activation of Factor X and the common pathway of coagulation.
Current research is focused on elucidating the precise mechanisms by which the contact activation system contributes to disease and identifying potential therapeutic targets within the cascade. The development of novel inhibitors that can selectively block components of the contact system without affecting the overall hemostatic balance is a key area of interest.


[[Category:Immunology]]
=== Clinical Significance ===
[[Category:Hematology]]
Deficiencies in components of the contact activation system, such as Factor XII deficiency, are often asymptomatic in terms of bleeding, as the intrinsic pathway can be bypassed by the extrinsic pathway in vivo. However, these deficiencies can lead to prolonged [[activated partial thromboplastin time]] (aPTT) in laboratory tests.
[[Category:Coagulation System]]


{{Medicine-stub}}
The contact system also plays a role in inflammation and [[angiogenesis]], and its dysregulation can contribute to pathological conditions such as [[hereditary angioedema]] and [[thrombosis]].
 
== Related Pages ==
* [[Coagulation]]
* [[Intrinsic pathway]]
* [[Extrinsic pathway]]
* [[Common pathway]]
* [[Bradykinin]]
 
[[Category:Coagulation system]]

Latest revision as of 05:50, 16 February 2025

Overview of the contact activation system in the coagulation cascade


Contact Activation System[edit]

The contact activation system is a crucial component of the coagulation cascade, which is responsible for initiating the intrinsic pathway of blood coagulation. This system is activated when blood comes into contact with negatively charged surfaces, such as glass or collagen, leading to a series of enzymatic reactions that ultimately result in the formation of a blood clot.

Diagram of the contact activation system

Components[edit]

The contact activation system involves several key proteins and enzymes, including:

  • Factor XII (Hageman factor): This is the first protein to be activated in the contact system. It is converted to its active form, Factor XIIa, upon contact with a negatively charged surface.
  • Prekallikrein: This is converted to kallikrein by Factor XIIa. Kallikrein further activates Factor XII, creating a positive feedback loop.
  • High-molecular-weight kininogen (HMWK): This acts as a cofactor, enhancing the activation of Factor XII and prekallikrein.
  • Factor XI: Activated by Factor XIIa, it plays a role in the downstream activation of the intrinsic pathway.

Mechanism[edit]

The activation of the contact system begins when Factor XII binds to a negatively charged surface. This binding induces a conformational change in Factor XII, allowing it to autoactivate to Factor XIIa. Factor XIIa then activates prekallikrein to kallikrein, which in turn further activates more Factor XII, amplifying the response.

Kallikrein also cleaves HMWK to release bradykinin, a peptide that increases vascular permeability and contributes to inflammation. Factor XIIa activates Factor XI, which then activates Factor IX, leading to the activation of Factor X and the common pathway of coagulation.

Clinical Significance[edit]

Deficiencies in components of the contact activation system, such as Factor XII deficiency, are often asymptomatic in terms of bleeding, as the intrinsic pathway can be bypassed by the extrinsic pathway in vivo. However, these deficiencies can lead to prolonged activated partial thromboplastin time (aPTT) in laboratory tests.

The contact system also plays a role in inflammation and angiogenesis, and its dysregulation can contribute to pathological conditions such as hereditary angioedema and thrombosis.

Related Pages[edit]

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