Regulatory Mechanisms and Fibrinolysis Student Outline.docx

Hemostatic System

Initiation & Propagation:The pathways of initiation and propagation in the hemostatic system are interdependent, involving cells expressing tissue factor and platelets in two distinct phases.

Initiation Phase

Involves the formation of the extrinsic tenase complex on tissue factor-expressing cells, leading to the generation of small amounts of thrombin and activation of platelets and procoagulants.

Propagation Phase

Occurs on platelets with more than 95% of thrombin generation, leading to the formation of COAT platelets with high procoagulant activity and the amplification of coagulation complexes.

Coagulation Regulatory Mechanisms

Maintain a balance between procoagulant and anticoagulant systems, involving regulators like Tissue Factor Pathway Inhibitor (TFPI), Antithrombin (AT), and Activated Protein C (APC).

Protein C Regulatory System

Involves thrombin-triggered activation of protein C by thrombomodulin, leading to the inactivation of factors Va and VIIIa, slowing down thrombin generation.

Fibrinolytic System

Involves the activation of fibrinolysis to remove unwanted fibrin deposits by plasmin, with activators like tissue plasminogen activator (TPA) and urokinase plasminogen activator (UPA).

Plasminogen Inhibitors

Include Plasminogen activator inhibitor-1 (PAI-1) and Alpha 2 antiplasmin, which regulate the activity of plasmin and protect fibrin from excessive degradation.

Fibrin Degradation Products (FDPs)

Result from the proteolytic degradation of fibrin and fibrinogen by plasmin, leading to the formation of D-dimers and interfering with further thrombin-induced fibrin formation.