Which of the following is the PRIMARY mechanism by which tissue factor (TF) initiates the coagulation cascade in disseminated intravascular coagulation (DIC)?
A. Inhibition of protein C and protein S anticoagulant pathways
B. Activation of Factor XII (Hageman factor) via contact pathway
C. Direct activation of Factor VII, leading to Factor X and II activation
D. Platelet aggregation-mediated thrombin generation
Explanation
Tissue Factor and DIC Pathogenesis
Key Point
Tissue factor (TF) is the primary trigger of coagulation in DIC and initiates the extrinsic pathway by binding to Factor VII.
Mechanism of TF-Mediated Coagulation
Tissue factor (also called thromboplastin) is released from:
Damaged endothelium
Monocytes (activated by cytokines like TNF-α, IL-1)
Cancer cells (especially adenocarcinomas)
TF binds to Factor VII (not Factor XII) to form the TF-Factor VIIa complex, which then:
1.
Directly activates Factor X → Factor Xa
2.
Factor Xa converts Factor II (prothrombin) → Thrombin (Factor IIa)
3.
Thrombin amplifies coagulation by activating Factors V, VIII, XI, and platelets
High-YieldNEET PG
This is the extrinsic pathway, not the contact (intrinsic) pathway. The extrinsic pathway is the primary initiator of DIC in most clinical scenarios.
Why This Matters in DIC
Once TF-Factor VIIa is activated, the cascade becomes self-perpetuating because:
Thrombin activates Factor XI → Factor XIa (amplification loop)
Thrombin activates platelets → platelet aggregation and microthrombi formation
In sepsis-induced DIC (the most common cause), endotoxin (LPS) triggers monocyte release of TF, explaining why gram-negative sepsis is a major DIC trigger.
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