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The page below is a sample from the LabCE course Fundamentals of Hemostasis. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Secondary Hemostasis – The Intrinsic Pathway

Exposure to contact substances, such as collagen, can activate the intrinsic pathway. The exposed collagen is the location where a complex between High Molecular Weight Kininogen (HMWK), Prekallikrein (also known as Fletcher Factor, which activates to Kallikrein), and factor XII (Hageman Factor) forms. Together, this biochemical complex, adhered to the collagen binding site, catalyzes the conversion of factor XII to its activated form, XIIa, thereby triggering the intrinsic pathway.
Here is where the “cascade” or “waterfall” nomenclature becomes evident as each activated factor triggers the conversion and activation of subsequent factors. Factor XIIa, activated previously, catalyzes the conversion of factor XI into XIa, while in the presence of HMWK.
Note: This reaction can occur without HMWK, but will be much slower.