The Contact Activator for the Intrinsic Pathway is Sub-endothelial Collagen
The correct answer is C: Sub-endothelial Collagen. Collagen serves as the primary physiological contact activator that initiates the intrinsic coagulation pathway through Factor XII activation. 1
Mechanism of Contact Activation
The intrinsic pathway is triggered by an activating surface, with sub-endothelial collagen being the key physiological activator that becomes exposed when blood contacts extravascular tissue during vascular injury. 1
Collagen activates Factor XII to Factor XIIa through direct binding, which then initiates the contact activation cascade involving the sequential activation of Factor XI, prekallikrein, and high molecular weight kininogen. 1, 2
Fibrillar type I collagen provokes Factor XII activation in a dose-dependent manner by providing a negatively charged surface for Factor XII binding and subsequent conformational change leading to autoactivation. 2, 3
Why the Other Options Are Incorrect
Tissue Thromboplastin (Option A) initiates the extrinsic pathway, not the intrinsic pathway—it acts as a receptor for Factor VII to form the TF-VIIa complex that triggers the extrinsic coagulation cascade. 1, 4
Calcium (Option B) is a cofactor required for coagulation, not an activator—it enables binding of certain coagulation factors (II, VII, IX, X) to procoagulant membranes but does not initiate the intrinsic pathway. 1
Factor VII (Option D) is part of the extrinsic pathway, binding to tissue factor rather than serving as a contact activator for the intrinsic pathway. 1, 4
Clinical Context of Contact Activation
Collagen plays a dual role in thrombus formation: it stimulates glycoprotein VI signaling on platelets to form procoagulant surfaces AND activates Factor XII to amplify thrombin generation through the intrinsic pathway. 2
Multiple negatively charged surfaces can activate Factor XII in pathological conditions, including misfolded protein aggregates, nucleic acids, and polyphosphates, but collagen remains the primary physiological activator during vascular injury. 5, 3
Glass was historically used to demonstrate contact activation in laboratory settings (such as in activated partial thromboplastin time testing), but this is an artificial activator—collagen represents the true in vivo contact activator. 1