User:Simoncaulton/sandbox

The two arms of the contact system.

The contact activation system or CAS involves three proteins: factor XII (FXII), prekallikrein (PK) and high molecular weight kiningogen (HK). FXII and PK are proteases and HK is a non-enzymatic co-factor. The CAS can activate the Kinin–kallikrein system and blood coagulation through its ability to activate multiple downstream proteins. The CAS is initiated when FXII binds to a surface and reciprocal activation of FXII and PK occurs, forming FXIIa and PKa. PK can activate factor XI (FXI), which can initiate the coagulation cascade. Additionally, PK cleaves HK to form cHK, and a peptide is released, known as bradykinin (BK). BK and its derivatives bind to bradykinin receptors B1 and B2 to mediate inflammation.

Surfaces

The contact system activates upon FXII's binding to negatively charged surfaces. This is observed routinely

Phyiological roles

Although the contact system can activate FXI and the subsequent clotting cascade, and it is routinely observed to activate coagulation in the presence of medical devices, the actual role of the contact system in normal physiological coagulation remains contentious. This is primarily due to the fact that deficiencies in the contact system proteins FXII, PK and HK do not produce bleeding disorders. FXI deficiency, however, does cause a mild bleeding disorder.