Mechanism of Action of Apixaban

Introduction

Apixaban is a direct oral anticoagulant (DOAC) used to prevent and treat thrombosis. It is specifically indicated for stroke prevention in non-valvular atrial fibrillation, treatment and prevention of venous thromboembolism (VTE), and management of deep vein thrombosis (DVT) and pulmonary embolism (PE). Its predictable pharmacokinetics and oral administration make it a widely used alternative to warfarin.

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Step-by-Step Mechanism of Action

1. Selective Factor Xa Inhibition
   Apixaban directly and reversibly inhibits both free and clot-bound factor Xa, without requiring antithrombin III.
2. Prevention of Prothrombinase Activity
   By blocking factor Xa, apixaban disrupts the prothrombinase complex, which converts prothrombin to thrombin.
3. Reduced Thrombin Generation
   With less thrombin produced, the conversion of fibrinogen to fibrin is inhibited, limiting clot formation and growth.
4. Antithrombotic Effect
   Blocking the central step in coagulation cascade prevents both arterial and venous thrombus development.
5. No Direct Platelet Effect
   Apixaban does not directly affect platelets, but reduces thrombin-mediated platelet activation indirectly.

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Pharmacokinetic Parameters

Parameter	Value
Route	Oral, twice daily
Bioavailability	~50%
Time to Peak (Tmax)	~3–4 hours
Protein Binding	~87%
Metabolism	Hepatic via CYP3A4 and CYP1A2
Half-life	~12 hours
Excretion	~27% renal, remainder via fecal/biliary

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Clinical Uses

• Stroke prevention in non-valvular atrial fibrillation
• Treatment and secondary prevention of DVT/PE
• VTE prophylaxis post-hip or knee replacement surgery

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Adverse Effects

• Increased risk of bleeding (most common)
• Minor: Bruising, epistaxis
• Major: Gastrointestinal bleeding, intracranial hemorrhage (less common than warfarin)
• Rare: Hypersensitivity, elevated liver enzymes

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Comparative Analysis

Agent	Factor Xa Inhibition	Monitoring	Reversal Agent
Apixaban	Direct, reversible	No	Andexanet alfa
Rivaroxaban	Direct, reversible	No	Andexanet alfa
Warfarin	Indirect (VKOR)	Yes (INR)	Vitamin K, PCCs

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MCQs

1. Apixaban acts by inhibiting which factor?
   a) Thrombin (IIa)
   b) Factor Xa
   c) Factor VIIa
   d) Factor IXa
   Answer: b) Factor Xa
2. It inhibits factor Xa in:
   a) Free form
   b) Clot-bound form
   c) Both
   d) Neither
   Answer: c) Both
3. Apixaban requires which cofactor for activity?
   a) Antithrombin III
   b) Calcium
   c) Vitamin K
   d) None
   Answer: d) None
4. Reduction in thrombin leads to:
   a) Increased fibrin formation
   b) Decreased clot formation
   c) Platelet aggregation activation
   d) Increased coagulation
   Answer: b) Decreased clot formation
5. Which describes apixaban’s effect on platelets?
   a) Direct inhibitor
   b) Activator
   c) No direct effect
   d) Irreversible binding
   Answer: c) No direct effect
6. Apixaban’s half-life is approximately:
   a) 4 hours
   b) 7 hours
   c) 12 hours
   d) 24 hours
   Answer: c) 12 hours
7. What percentage is excreted renally?
   a) ~10%
   b) ~27%
   c) ~50%
   d) >70%
   Answer: b) ~27%
8. The antidote for apixaban bleeding is:
   a) Vitamin K
   b) Protamine
   c) Andexanet alfa
   d) Fresh frozen plasma
   Answer: c) Andexanet alfa
9. Compared to warfarin, apixaban requires:
   a) Regular INR monitoring
   b) Fixed dosing without monitoring
   c) Frequent dose adjustments
   d) Dietary restrictions
   Answer: b) Fixed dosing without monitoring
10. The time to peak plasma levels is:
    a) 1 hour
    b) 3–4 hours
    c) 8 hours
    d) 24 hours
    Answer: b) 3–4 hours

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FAQs

1. Is routine monitoring needed with apixaban?
No—fixed dosing eliminates the need for INR testing.

2. Can apixaban be used in renal impairment?
Yes—but dose adjustments are required when eGFR <30 mL/min.

3. How long before surgery should apixaban be stopped?
Typically, 24–48 hours before, depending on bleeding risk and renal function.

4. Does apixaban interact with other medications?
Yes—CYP3A4 and P-gp inhibitors or inducers may require dose adjustment.

5. Is the bleeding risk lower than warfarin?
Apixaban has been shown to reduce major and intracranial bleeding compared to warfarin.

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References

• DrugBank: Apixaban mechanism and pharmacology
• StatPearls: Apixaban clinical pharmacology
• PubMed/PMC: Pharmacodynamic review of apixaban
• Mayo Clinic: Apixaban clinical use overview
• Stroke Manual: Mechanism of apixaban