Phospholipid Activator for the Extrinsic Pathway
The correct answer is A: Tissue Thromboplastin (Tissue Factor), which functions as the phospholipid-associated activator that initiates the extrinsic coagulation pathway.
Mechanism of the Extrinsic Pathway
Tissue Factor (TF), also known as tissue thromboplastin or CD142, is the transmembrane receptor that binds Factor VII/VIIa to initiate the extrinsic pathway of coagulation. 1, 2 This complex forms on phospholipid membrane surfaces and represents the primary physiological trigger for blood coagulation. 3
Essential Components Required
The extrinsic pathway requires three critical elements working together:
- Tissue Factor (TF): The transmembrane protein that serves as the cellular receptor and cofactor for Factor VII 2, 3
- Phosphatidylserine (PS): The negatively charged phospholipid membrane surface that enables the TF-Factor VIIa complex to assemble and achieve optimal catalytic activity 1
- Calcium ions (Ca²⁺): Required for binding coagulation factors to the pro-coagulant phospholipid membrane 1, 2
Why the Other Options Are Incorrect
Calcium (Option B): While calcium is essential as a cofactor for binding coagulation factors to phospholipid surfaces, it is not the phospholipid activator itself. 1, 4 Calcium enables the assembly but does not initiate the pathway.
Sub-endothelial Collagen (Option C): Collagen triggers the intrinsic pathway through Factor XII contact activation, not the extrinsic pathway. 5, 6 This represents a common pitfall in understanding the distinction between the two pathways.
Factor XII (Option D): Factor XII is activated by negatively charged surfaces to initiate the intrinsic pathway, not the extrinsic pathway. 6 Factor XII activation occurs through contact with surfaces like glass or collagen, representing a fundamentally different mechanism.
Clinical Context
TF is constitutively expressed by adventitial cells surrounding blood vessels and initiates clotting under physiological conditions. 3 The TF-Factor VIIa complex forms in a 1:1 stoichiometric ratio on phospholipid membranes, rapidly activating both Factor IX and Factor X to propagate the coagulation cascade. 2, 7
The extrinsic pathway represents the primary physiological mechanism for hemostasis at sites of vessel injury, where exposure of TF to flowing blood triggers immediate coagulation responses. 3