Understanding Hemostasis and Coagulation

Aug 23, 2024

Hemostasis Overview

Key Concepts

  • Hemostasis is divided into:
    • Primary Hemostasis: Involves platelet plug formation.
    • Secondary Hemostasis: Involves the coagulation cascade.

Coagulation Cascade

Pathways

  • Extrinsic Pathway:
    • Triggered by tissue injury.
    • Tissue factor and factor 7a activate factor 10 to 10a.
  • Intrinsic Pathway:
    • Initiated by negatively charged surfaces.
    • Activates factors 12, 11, 9, 8 sequentially.
  • Common Pathway:
    • Both pathways activate factor 10.
    • Factor 10a and 5a activate prothrombin to thrombin (factor 2a).
    • Thrombin converts fibrinogen to fibrin (factor 1a), reinforcing the platelet plug.

Role of Calcium

  • Critical in several steps of the coagulation cascade.

Cell-Based Model of Coagulation

Steps

  1. Initiation:
    • Tissue factor and factor 7a interaction starts thrombin activation.
  2. Amplification:
    • Small thrombin amounts activate factors 5, 8, and 11.
    • Activated platelets enhance thrombin generation.
  3. Propagation:
    • Formation of prothrombinase complex on platelets converts prothrombin to thrombin.

Fibrinolysis

  • Breakdown of fibrin by plasmin (from plasminogen activated by tPA).
  • Fibrinolytic Inhibitors:
    • Thrombin Activatable Fibrinolysis Inhibitor: Slows fibrinolysis.
    • Plasmin Activator Inhibitor (PAI-1): Inhibits tPA and plasmin formation.
    • Alpha2 Antiplasmin: Directly inhibits plasmin activity.
    • Tranexamic Acid: Used to stop bleeding by inhibiting tPA.

Control Mechanisms of Coagulation

Antithrombotic Pathways

  • Protein C and Protein S:
    • Thrombin binds thrombomodulin, activating protein C.
    • Protein C with Protein S inhibits factors 5a and 8a.
  • Tissue Factor Pathway Inhibitor (TFPI):
    • Inhibits factor 10a and tissue factor-factor 7a complex.
  • C1 Esterase Inhibitor:
    • Inhibits factors 11a, 12a, and complement proteases C1r and C1s.
    • Deficiency can lead to hereditary angioedema.
  • Antithrombin:
    • Neutralizes enzymes in the cascade, inhibiting thrombin, factor 10a, and 9a.

Summary

  • Discussed classical and cell-based models of coagulation.
  • Introduced fibrinolysis and its control mechanisms.
  • Explained antithrombotic pathways managing coagulation.

Note: Understanding coagulation is crucial for interpreting coagulation tests and identifying bleeding disorders.