Contact activation system

Overview of the contact activation system in the coagulation cascade

Contact Activation System

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

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

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

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

• Coagulation
• Intrinsic pathway
• Extrinsic pathway
• Common pathway
• Bradykinin