An overview of the clotting cascade:
1. Initiation:
Platelets adhere to vessel and ❌ more circulating platelets to ❌. This provides a surface
where clotting factors assemble. Some clotting factors are ❌. TF initiates coagulation. TF activates ❌, forming Xa and IXa.
2. Amplification
IXa amplifies the activation of ❌. The ❌ complex is a critical component, activating ❌ (thrombin)
3. Propagation
A burst of activated thrombin then converts ❌, to form a mesh.

The clotting cascade has an "❌ pathway" activated by trauma inside the vascular system. It is ❌ than the “extrinsic pathway”. The initiation involves XII, XI, IX, VIII.

Unfractionated heparin is found naturally in ❌ cells. It is a large ❌ with alternating disaccharide units of variable lengths.
- No ❌ anticoagulant activity
- Not ❌ available so given intravenously and subcutaneously
- Half-life of about ❌ hour
The antidote is a reversal agent called ❌.
It binds to ❌I, and induces a conformational change that enhances binding to ❌ clotting actors, helping to inhibit coagulation.

Low molecular weight heparins (LMWH)
• Given ❌
• Enoxaparin halfe life ~ ❌
• Mainly ❌-cleared
• Effect ❌ reversed by giving protamine sulphate
• Target is mostly anti-❌, some anti-IIa

Novel oral anticoagulants (NOACs):
1. Dabigatran etexilate
• Competitive and reversible inhibition of free and clot bound ❌
• Prodrug converted to active compound (dabigatran)
• ❌ oral availability (~7%)
• ~80% ❌ cleared, ~20% glucuronidation
• Half life: ~12 hours
2. Rivaroxaban
• Competitive and reversible inhibition of free and clot bound ❌
• ❌ oral availability (>80%)
• ~35% renally cleared, ~65% ❌ (CYP3A4 and others)
• Half life: ~7-10 hours

PT, prothrombin time, is the time taken for plasma to clot in ❌ after the addition of ❌. Normally it is 12-15 seconds. The PT ratio is the ❌ PT over the normal ❌ PT.
The International Normalised ratio (INR) is a “correction” of the PT ratio, or rather a correction of the large variability in the ❌.
Low INR indicates a risk for ❌ while high INR indicates a risk for ❌. The usual range is 2-3.

Most clinically important interactions with warfarin are well understood and can be predicted.
I.e these drugs:
• Inhibition of CYP2C9, e.g. ❌
• Induction of CYPs, e.g. ❌
• Inhibition if CYP3A4, 1A2 e.g. ❌
Will affect the warfarin metabolism significantly.

Thrombolytic drugs (also called fibrinolytics) work by activating ❌, to produce plasmin. ❌ breaks cross-links between ❌ molecules, disrupting the structural integrity of blood clots. They restore blood flow more ❌ than anticoagulants but carry a much higher ❌ of bleeding.