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Understanding the Coagulation Cascade

Apr 30, 2025

Coagulation Cascade Lecture Notes

Overview

  • The coagulation cascade is a complex process learned multiple times during medical education.
  • It includes intrinsic and extrinsic pathways, lab tests, and interaction with various drugs.

Pathways of Coagulation

Intrinsic Pathway

  • Color Code: Red
  • Initiation: Contact activation (surface damage)
  • Factors Involved: 12, 11, 9, 8

Extrinsic Pathway

  • Color Code: Blue
  • Initiation: Trauma or inflammation leading to tissue factor release
  • Factors Involved:
    • Tissue factor (Factor 3)
    • Factor 7
  • Activation: Factor 7 and tissue factor complex activates Factor 10

Common Pathway

  • Color Code: Purple
  • Activation: Both pathways activate Factor 10
  • Process:
    • Activated Factor 10 converts prothrombin to thrombin (Factor 2)
    • Thrombin cleaves fibrinogen into fibrin (Factor 1)
    • Leads to clot formation

Additional Factors

  • Factor 5: Cofactor, needed alongside calcium for Factor 10 to convert prothrombin into thrombin.

Tricks to Remember Pathways

  • Intrinsic Pathway: "Countdown" 12, 11, 9, 8.
  • Extrinsic Pathway: Factors 3 (tissue factor) + 7 = 10, written as X.

Laboratory Tests

PTT (Activated Thromboplastin Time)

  • Assesses the intrinsic pathway
  • Normal Range: 25 to 29 seconds

PT (Prothrombin Time)

  • Assesses the extrinsic pathway
  • Normal Range: About 12 seconds

Test Memory Trick

  • "Play table tennis (PTT) inside, play tennis (PT) outside."
  • Both tests assess the common pathway as well.

Vitamin K Dependent Factors

  • Factors: 2, 7, 9, 10

Causes for Prolonged Test Times

Prolonged PTT, Normal PT

  • Factor 8 deficiency (Hemophilia A, Von Willebrand's disease)
  • Factor 9 deficiency (Hemophilia B)
  • Factor 11 or 12 deficiencies

Prolonged PT, Normal PTT

  • Factor 7 deficiency
  • Early vitamin K antagonism, disseminated intravascular coagulation

Prolonged PT and PTT

  • Decreased vitamin K activity
  • Severe disseminated intravascular coagulation
  • Liver disease
  • High doses of heparin or direct oral anticoagulants

Drugs Affecting Coagulation

Heparin

  • Binds to antithrombin 3, inhibiting activated Factor 10 and thrombin

Low Molecular Weight Heparins

  • Similar action to heparin but more specific to activated Factor 10

Warfarin

  • Vitamin K reductase inhibitor
  • Inhibits synthesis of Vitamin K dependent factors
  • Initial pro-clotting effect due to Protein C and S inhibition

Direct Oral Anticoagulants (DOACs/NOACs)

  • Examples:
    • Rivaroxaban, Apixaban: Direct Factor 10 inhibitors
    • Dabigatran: Direct thrombin inhibitor

Antidotes for Anticoagulants

Heparin Reversal

  • Protamine Sulfate: Binds and neutralizes heparin/low molecular weight heparin

Warfarin Reversal

  • Vitamin K: Long-term reversal
  • Fresh Frozen Plasma/Prothrombin Complex Concentrate: Immediate reversal

DOACs Reversal

  • Idarucizumab: Antidote for Dabigatran
  • Andexanet Alfa: Antidote for direct Factor 10 inhibitors

These notes provide a high-level overview of the coagulation cascade and its clinical implications, including how drugs interact with different parts of the pathway and their reversal agents.

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