Coagulation Cascade Overview

Introduction

• The coagulation cascade is a complex process learned repeatedly in medical school.
• Common areas of confusion:
  • Differentiating intrinsic and extrinsic pathways.
  • Tests used to assess each pathway.
  • Sites of action for different drugs.

Pathways of Coagulation Cascade

Intrinsic Pathway (Red)

• Triggered by contact activation due to surface damage.
• Involves factors: 12, 11, 9, and 8.

Extrinsic Pathway (Blue)

• Triggered by trauma or inflammation causing tissue factor release.
• Tissue factor is also known as Factor 3.
• Involves factors: 7 and 3 (tissue factor).
• Factor 7 and tissue factor complex activate Factor 10.

Common Pathway (Purple)

• Where intrinsic and extrinsic pathways meet.
• Factor 10 activation leads to:
  • Conversion of prothrombin (Factor 2) to thrombin.
  • Thrombin cleaves fibrinogen into fibrin (Factor 1), forming a clot.

Factor Role

• Factor 5: Cofactor, not enzymatically active, required with calcium for Factor 10 activation of prothrombin.

Memorization Tricks

• Intrinsic Pathway: Countdown in intrinsic pathway: 12, 11, 9, 8.
• Extrinsic Pathway: Factors 7 and 3 add up to 10 (X in Roman numerals).

Laboratory Tests

• PTT (Partial Thromboplastin Time): Evaluates intrinsic and common pathways.
• PT (Prothrombin Time): Evaluates extrinsic and common pathways.
• Memory Aid: Table tennis (PTT) inside (intrinsic); tennis (PT) outside (extrinsic).
• Normal Range: PTT (25-29 seconds), PT (~12 seconds), but varies per lab.

Vitamin K Dependent Factors

• Factors: 2, 7, 9, 10.

Prolonged Test Times

• Prolonged PTT, Normal PT:
  • Factor deficiencies: 8 (Hemophilia A, Von Willebrand's), 9 (Hemophilia B), 11, 12.
• Prolonged PT, Normal PTT:
  • Factor 7 deficiency.
  • Possible initial DIC or early vitamin K antagonism.
• Both PT and PTT Prolonged:
  • Decreased vitamin K activity.
  • Liver disease, DIC.
  • High doses of heparin or direct oral anticoagulants.

Drug Actions and Reversals

• Heparin: Binds to antithrombin 3, inhibiting Factor 10 and thrombin.
• Low Molecular Weight Heparins: More specific for Factor 10.
• Warfarin: Vitamin K reductase inhibitor, decreases vitamin K dependent factor synthesis.
• Direct Oral Anticoagulants (DOACs/NOACs):
  • Rivaroxaban, apixaban: Factor 10 inhibitors.
  • Dabigatran: Thrombin inhibitor.
• Antidotes:
  • Heparin: Protamine sulfate.
  • Warfarin: Vitamin K, fresh frozen plasma, PCC.
  • Dabigatran: Idarucizumab.
  • Factor 10 inhibitors: Andexanet alfa.