PA20.1-2 | Normal Haemostasis — Summary & Reflection

REFLECT

Before moving on, pause and think through this scenario:

A 62-year-old woman on warfarin for atrial fibrillation is started on a 10-day course of ciprofloxacin for a urinary tract infection. One week later, her INR has risen from a stable 2.5 to 5.8, and she has bruising.

• Which vitamin K–dependent factors are being affected?
• Ciprofloxacin kills gut bacteria. Which of those bacteria synthesise vitamin K₂? How does this interact with warfarin?
• Her PT is markedly prolonged but her aPTT is only slightly prolonged. Which factor's half-life explains why the PT moves first?
• If she were also found to have a PE, would you reverse the warfarin? What agent would you use?

Discuss your reasoning with a peer. There is no single 'correct' structured answer — the goal is to apply the cascade map you've just built.

KEY TAKEAWAYS

Normal haemostasis operates as a three-component, tightly regulated system:

1. Primary haemostasis — vasoconstriction + platelet adhesion (GPIb–vWF–collagen) + activation (ADP, TxA₂) + aggregation (GPIIb/IIIa–fibrinogen) → platelet plug. Tested by: bleeding time, PFA-100, platelet count.

1. Secondary haemostasis — coagulation cascade (intrinsic: XII→XI→IX+VIII; extrinsic: TF+VII; common: X→V→II→I→fibrin→XIII cross-link) → fibrin-reinforced stable clot. Tested by: PT (extrinsic+common), aPTT (intrinsic+common), TT (fibrinogen/final step). The cell-based model (initiation→amplification→propagation on platelet surface) is the physiologically accurate framework.

1. Fibrinolysis — plasminogen→plasmin via tPA → fibrin dissolution → FDPs and D-dimer. Regulated by PAI-1 and α₂-antiplasmin.

Natural anticoagulants (antithrombin, Protein C+S, TFPI) maintain balance and prevent systemic thrombosis.

Vitamin K–dependent factors: II, VII, IX, X (pro-coagulant) + Protein C, Protein S (anti-coagulant). Warfarin depletes all six; VII and Protein C fall first (shortest half-lives).

Thrombin is the central effector: cleaves fibrinogen, activates V/VIII/XIII/platelets, and — on intact endothelium via thrombomodulin — activates Protein C (anticoagulant feedback).

SDL 2 next: Platelet and vascular bleeding disorders — now you have the framework to understand exactly what breaks.