Antiplatelet & Anticoagulant Drugs
For PharmD & Clinical Practice
📌
Core Principles
Clinical Pharmacist Role
- Balance thrombosis prevention vs bleeding risk
- Optimize drug choice, dose, duration
- Manage peri-operative interruption & reversal
- Adapt guidelines to Egyptian hospital realities
🧠
Part I — Antiplatelet Agents
1️⃣ Classification
| Class | Drugs | Mechanism | Onset / Offset |
|---|---|---|---|
| COX-1 | Aspirin | Irreversible TXA₂ inhibition | 1 h / 5–7 days |
| P2Y₁₂ | Clopidogrel, Prasugrel, Ticagrelor | Block ADP receptor |
Clopidogrel: 2-6 h / 5 d Ticagrelor: 2 h / 3-5 d Prasugrel: 30 min / 7 d |
| GPIIb/IIIa (IV) | Tirofiban, Eptifibatide | Block fibrinogen binding | Minutes / 4-8 h |
Key Points
- Clopidogrel: Prodrug (CYP2C19), ~30% poor metabolizers
- Ticagrelor: Direct-acting, preferred in high-risk ACS
- Prasugrel: Contraindicated if age >75y, weight <60kg, or prior stroke
2️⃣ Major Indications & Duration
| Setting | Regimen | Duration |
|---|---|---|
| ACS + PCI | DAPT (Aspirin + P2Y₁₂) | 12 months (standard) 1-6 months if high bleeding risk |
| ACS + PCI (High Bleeding Risk) | DAPT ×1 month → P2Y₁₂ mono | Ticagrelor preferred |
| ACS + Anticoagulant | Triple ×1 week → Dual ×12 months | Then OAC alone |
| Chronic CAD | Clopidogrel mono | Lifelong |
| Stroke/TIA | Aspirin or Clopidogrel mono | Lifelong |
| PAD | Clopidogrel mono | Lifelong |
New 2025 Guideline Update:
High bleeding risk patients: Ticagrelor monotherapy after 1 month DAPT (Class 1 recommendation)
High bleeding risk patients: Ticagrelor monotherapy after 1 month DAPT (Class 1 recommendation)
3️⃣ Dosing
| Drug | Loading | Maintenance |
|---|---|---|
| Aspirin | 150-325 mg | 75-100 mg daily |
| Clopidogrel | 300-600 mg | 75 mg daily |
| Ticagrelor | 180 mg | 90 mg BID |
| Prasugrel | 60 mg | 10 mg daily (5 mg if <60 kg or >75 y) |
4️⃣ Pre-Surgery Hold Times
| Aspirin | Clopidogrel | Prasugrel | Ticagrelor |
|---|---|---|---|
| 5-7 d* | 5 d | 7 d | 3-5 d |
*May continue for cardiovascular procedures
5️⃣ Thrombocytopenia Management
| Platelets (×10⁹/L) | Action |
|---|---|
| >100 | Continue |
| 50-100 | Aspirin only if essential |
| <50 | STOP all antiplatelets |
6️⃣ Critical Interactions
- Clopidogrel + Omeprazole: Prefer Pantoprazole
- Antiplatelet + NSAID: Avoid or add PPI
- Ticagrelor + Strong CYP3A4 inhibitors: Contraindicated (ketoconazole, clarithromycin)
7️⃣ High Bleeding Risk (ARC-HBR)
Patient is HBR if: ≥1 Major OR ≥2 Minor criteria
Major Criteria (select):
- Long-term anticoagulation
- CrCl <30 or dialysis
- Hemoglobin <11 g/dL
- Prior ICH
- Active malignancy
- Platelets <100,000
Minor Criteria (select):
- Age ≥75 years
- CrCl 30-59
- Hemoglobin 11-12.9 (M) or 11-11.9 (F)
- Long-term NSAID/steroid use
Action if HBR: Shorten DAPT to 1-3 months → P2Y₁₂ monotherapy
🧪
Part II — Anticoagulant Agents
1️⃣ Classification
| Type | Drugs | Route | Monitoring | Reversal |
|---|---|---|---|---|
| UFH | Heparin | IV/SC | aPTT (1.5-2.5×) | Protamine (complete) |
| LMWH | Enoxaparin | SC | Anti-Xa (optional) | Protamine (60%) |
| VKA | Warfarin | PO | INR | Vit K + PCC |
| DOAC (Xa) | Apixaban, Rivaroxaban | PO | CrCl | Andexanet / PCC |
| DOAC (IIa) | Dabigatran | PO | CrCl | Idarucizumab / PCC |
2️⃣ First-Line Choices
| Indication | First Choice | Notes |
|---|---|---|
| VTE prophylaxis | Enoxaparin 40 mg SC daily | 20 mg if CrCl <30 |
| VTE treatment | DOAC (if CrCl >30) | UFH if unstable |
| Atrial Fibrillation | DOAC preferred | Warfarin if valve/cost issue |
| Mechanical valve | Warfarin ONLY | DOACs contraindicated |
| CrCl <15 | UFH or Warfarin | Avoid LMWH & DOACs |
3️⃣ DOAC Renal Dosing (AF) — CORRECTED
| Drug | CrCl >50 | CrCl 30-50 | CrCl 15-30 | CrCl <15 |
|---|---|---|---|---|
| Apixaban | 5 mg BID* | 5 mg BID* | 2.5 mg BID | Avoid |
| Rivaroxaban | 20 mg daily | 15 mg daily | 15 mg daily | Avoid |
| Dabigatran | 150 mg BID | 150 mg BID | Avoid | Avoid |
🔴 CRITICAL APIXABAN DOSE REDUCTION:
Reduce to 2.5 mg BID if ≥2 of (REGARDLESS of CrCl):
- Age ≥80 years
- Weight ≤60 kg
- Serum Creatinine ≥1.5 mg/dL
4️⃣ Enoxaparin Dosing
| CrCl | Prophylaxis | Treatment |
|---|---|---|
| >30 | 40 mg daily | 1 mg/kg BID |
| 15-30 | 20 mg daily | 1 mg/kg daily* |
| <15 | Avoid (use UFH) | Avoid (use UFH) |
*Consider switch to UFH preferred
5️⃣ Warfarin INR Management
| INR | No Bleeding | Bleeding |
|---|---|---|
| 3-5 | Hold 1-2 doses | Vit K 2.5-5 mg |
| 5-9 | Hold + Vit K 1-2.5 mg PO | Vit K 5 mg IV |
| >9 | Hold + Vit K 5 mg PO | Vit K 10 mg IV + PCC |
Key Points
- Minimum 5 days overlap with heparin/LMWH
- Target INR ≥2 × 2 consecutive days before stopping bridge
⚠️ Common Anticoagulant Errors
- No renal adjustment (CrCl <30)
- Insufficient warfarin overlap (<5 days or INR <2)
- Forgetting apixaban dose reduction criteria
- Using LMWH/DOAC in severe renal impairment
- Underdosing enoxaparin in obesity
🩸
Part III — Bleeding & Reversal
Quick Reversal Table
| Agent | Reversal | Dose |
|---|---|---|
| UFH | Protamine | 1 mg per 100 U (max 50 mg) |
| LMWH | Protamine (partial) | 1 mg per 1 mg enoxaparin if <8h |
| Warfarin | Vit K + PCC | Vit K 10 mg IV + PCC 50 U/kg |
| Dabigatran | Idarucizumab | 5 g IV |
| Xa inhibitors | Andexanet / PCC | PCC 50 U/kg (if no andexanet) |
| Antiplatelets | Platelet transfusion | 1 unit/10 kg |
⚠️ Andexanet: Thromboembolism risk ≈10.7%
Restarting After Bleeding
| Agent | Minor Bleed | Major Bleed |
|---|---|---|
| Antiplatelets | 24-48 h | 48-72 h |
| Heparin/LMWH | 24 h | 48-72 h |
| Warfarin | 24-48 h | 48-72 h |
| DOACs | 24-48 h | ≥72 h |
📋
Part IV — Pharmacist Checklist
Before Approving:
- Indication (arterial vs venous)
- CrCl calculated (Cockcroft-Gault)
- Platelets <48 h
- INR/aPTT ≤72 h
- Interactions checked
- No duplicate therapy
- Bleeding risk assessed (HAS-BLED, ARC-HBR)
- Duration defined
- Patient counseling documented
🧭
Part V — Decision Flow
Indication
- Arterial → Antiplatelet
- Venous → Anticoagulant
Renal Function
- CrCl ≥30 → DOAC / LMWH
- CrCl <30 → UFH / Warfarin
Bleeding Risk
- High → Shorter DAPT + PPI
- Low-Moderate → Standard duration
🧠
Part VI — Clinical Scenarios
1
Post-PCI ACS + Sepsis, Platelets 70K:
→ Clopidogrel only + PPI
→ Clopidogrel only + PPI
2
AF on Warfarin, NPO for surgery:
→ Hold warfarin 5d → Bridge with enoxaparin → Resume post-op
→ Hold warfarin 5d → Bridge with enoxaparin → Resume post-op
3
DVT on Enoxaparin, CrCl drops to 25:
→ Switch to UFH or reduce to 1 mg/kg daily
→ Switch to UFH or reduce to 1 mg/kg daily
4
ICH + INR 5.2:
→ Vit K 10 mg IV + PCC STAT
→ Vit K 10 mg IV + PCC STAT
5
Post-op DVT prophylaxis:
→ Enoxaparin 40 mg SC after 12-24h
→ Enoxaparin 40 mg SC after 12-24h
6
Mechanical valve + recent stent:
→ Triple ×1 week → Dual ×6 months → Warfarin alone
→ Triple ×1 week → Dual ×6 months → Warfarin alone
🧾
Part VII — Quick Scores
CHA₂DS₂-VASc
≥2 (male) or ≥3 (female) → Anticoagulate
HAS-BLED
≥3 = High bleeding risk → Modify factors (NOT contraindication)
🇪🇬 Egyptian Practical Notes
Drug Availability:
- Ticagrelor often unavailable → Clopidogrel 600 mg load acceptable
- GPIIb/IIIa → Cath lab only
- Use trusted clopidogrel generics
Cost-Effective Choices:
- VTE prophylaxis: Enoxaparin 40 mg
- AF anticoagulation: Apixaban or rivaroxaban (vs warfarin monitoring burden)
- ACS DAPT: Aspirin + clopidogrel (most affordable)
🎓
Key Takeaways
- DAPT duration: 12 months standard, 1-3 months if high bleeding risk
- Apixaban dosing: Reduce to 2.5 mg BID if ≥2 criteria (age ≥80, weight ≤60 kg, Cr ≥1.5)
- Renal adjustment: ALWAYS for LMWH/DOACs
- Warfarin overlap: Minimum 5 days + INR ≥2 × 2 days
- HAS-BLED ≥3: High risk but NOT contraindication—optimize modifiable factors
Antiplatelet & Anticoagulant Drugs
For PharmD & Clinical Practice
📌
Core Principles
Clinical Pharmacist Role
- Balance thrombosis prevention vs bleeding risk
- Optimize drug choice, dose, duration
- Manage peri-operative interruption & reversal
- Adapt guidelines to Egyptian hospital realities
🧠
Part I — Antiplatelet Agents
1️⃣ Classification
| Class | Drugs | Mechanism | Onset / Offset |
|---|---|---|---|
| COX-1 | Aspirin | Irreversible TXA₂ inhibition | 1 h / 5–7 days |
| P2Y₁₂ | Clopidogrel, Prasugrel, Ticagrelor | Block ADP receptor |
Clopidogrel: 2-6 h / 5 d Ticagrelor: 2 h / 3-5 d Prasugrel: 30 min / 7 d |
| GPIIb/IIIa (IV) | Tirofiban, Eptifibatide | Block fibrinogen binding | Minutes / 4-8 h |
Key Points
- Clopidogrel: Prodrug (CYP2C19), ~30% poor metabolizers
- Ticagrelor: Direct-acting, preferred in high-risk ACS
- Prasugrel: Contraindicated if age >75y, weight <60kg, or prior stroke
2️⃣ Major Indications & Duration
| Setting | Regimen | Duration |
|---|---|---|
| ACS + PCI | DAPT (Aspirin + P2Y₁₂) | 12 months (standard) 1-6 months if high bleeding risk |
| ACS + PCI (High Bleeding Risk) | DAPT ×1 month → P2Y₁₂ mono | Ticagrelor preferred |
| ACS + Anticoagulant | Triple ×1 week → Dual ×12 months | Then OAC alone |
| Chronic CAD | Clopidogrel mono | Lifelong |
| Stroke/TIA | Aspirin or Clopidogrel mono | Lifelong |
| PAD | Clopidogrel mono | Lifelong |
New 2025 Guideline Update:
High bleeding risk patients: Ticagrelor monotherapy after 1 month DAPT (Class 1 recommendation)
High bleeding risk patients: Ticagrelor monotherapy after 1 month DAPT (Class 1 recommendation)
3️⃣ Dosing
| Drug | Loading | Maintenance |
|---|---|---|
| Aspirin | 150-325 mg | 75-100 mg daily |
| Clopidogrel | 300-600 mg | 75 mg daily |
| Ticagrelor | 180 mg | 90 mg BID |
| Prasugrel | 60 mg | 10 mg daily (5 mg if <60 kg or >75 y) |
4️⃣ Pre-Surgery Hold Times
| Aspirin | Clopidogrel | Prasugrel | Ticagrelor |
|---|---|---|---|
| 5-7 d* | 5 d | 7 d | 3-5 d |
*May continue for cardiovascular procedures
5️⃣ Thrombocytopenia Management
| Platelets (×10⁹/L) | Action |
|---|---|
| >100 | Continue |
| 50-100 | Aspirin only if essential |
| <50 | STOP all antiplatelets |
6️⃣ Critical Interactions
- Clopidogrel + Omeprazole: Prefer Pantoprazole
- Antiplatelet + NSAID: Avoid or add PPI
- Ticagrelor + Strong CYP3A4 inhibitors: Contraindicated (ketoconazole, clarithromycin)
7️⃣ High Bleeding Risk (ARC-HBR)
Patient is HBR if: ≥1 Major OR ≥2 Minor criteria
Major Criteria (select):
- Long-term anticoagulation
- CrCl <30 or dialysis
- Hemoglobin <11 g/dL
- Prior ICH
- Active malignancy
- Platelets <100,000
Minor Criteria (select):
- Age ≥75 years
- CrCl 30-59
- Hemoglobin 11-12.9 (M) or 11-11.9 (F)
- Long-term NSAID/steroid use
Action if HBR: Shorten DAPT to 1-3 months → P2Y₁₂ monotherapy
🧪
Part II — Anticoagulant Agents
1️⃣ Classification
| Type | Drugs | Route | Monitoring | Reversal |
|---|---|---|---|---|
| UFH | Heparin | IV/SC | aPTT (1.5-2.5×) | Protamine (complete) |
| LMWH | Enoxaparin | SC | Anti-Xa (optional) | Protamine (60%) |
| VKA | Warfarin | PO | INR | Vit K + PCC |
| DOAC (Xa) | Apixaban, Rivaroxaban | PO | CrCl | Andexanet / PCC |
| DOAC (IIa) | Dabigatran | PO | CrCl | Idarucizumab / PCC |
2️⃣ First-Line Choices
| Indication | First Choice | Notes |
|---|---|---|
| VTE prophylaxis | Enoxaparin 40 mg SC daily | 20 mg if CrCl <30 |
| VTE treatment | DOAC (if CrCl >30) | UFH if unstable |
| Atrial Fibrillation | DOAC preferred | Warfarin if valve/cost issue |
| Mechanical valve | Warfarin ONLY | DOACs contraindicated |
| CrCl <15 | UFH or Warfarin | Avoid LMWH & DOACs |
3️⃣ DOAC Renal Dosing (AF) — CORRECTED
| Drug | CrCl >50 | CrCl 30-50 | CrCl 15-30 | CrCl <15 |
|---|---|---|---|---|
| Apixaban | 5 mg BID* | 5 mg BID* | 2.5 mg BID | Avoid |
| Rivaroxaban | 20 mg daily | 15 mg daily | 15 mg daily | Avoid |
| Dabigatran | 150 mg BID | 150 mg BID | Avoid | Avoid |
🔴 CRITICAL APIXABAN DOSE REDUCTION:
Reduce to 2.5 mg BID if ≥2 of (REGARDLESS of CrCl):
- Age ≥80 years
- Weight ≤60 kg
- Serum Creatinine ≥1.5 mg/dL
4️⃣ Enoxaparin Dosing
| CrCl | Prophylaxis | Treatment |
|---|---|---|
| >30 | 40 mg daily | 1 mg/kg BID |
| 15-30 | 20 mg daily | 1 mg/kg daily* |
| <15 | Avoid (use UFH) | Avoid (use UFH) |
*Consider switch to UFH preferred
5️⃣ Warfarin INR Management
| INR | No Bleeding | Bleeding |
|---|---|---|
| 3-5 | Hold 1-2 doses | Vit K 2.5-5 mg |
| 5-9 | Hold + Vit K 1-2.5 mg PO | Vit K 5 mg IV |
| >9 | Hold + Vit K 5 mg PO | Vit K 10 mg IV + PCC |
Key Points
- Minimum 5 days overlap with heparin/LMWH
- Target INR ≥2 × 2 consecutive days before stopping bridge
⚠️ Common Anticoagulant Errors
- No renal adjustment (CrCl <30)
- Insufficient warfarin overlap (<5 days or INR <2)
- Forgetting apixaban dose reduction criteria
- Using LMWH/DOAC in severe renal impairment
- Underdosing enoxaparin in obesity
🩸
Part III — Bleeding & Reversal
Quick Reversal Table
| Agent | Reversal | Dose |
|---|---|---|
| UFH | Protamine | 1 mg per 100 U (max 50 mg) |
| LMWH | Protamine (partial) | 1 mg per 1 mg enoxaparin if <8h |
| Warfarin | Vit K + PCC | Vit K 10 mg IV + PCC 50 U/kg |
| Dabigatran | Idarucizumab | 5 g IV |
| Xa inhibitors | Andexanet / PCC | PCC 50 U/kg (if no andexanet) |
| Antiplatelets | Platelet transfusion | 1 unit/10 kg |
⚠️ Andexanet: Thromboembolism risk ≈10.7%
Restarting After Bleeding
| Agent | Minor Bleed | Major Bleed |
|---|---|---|
| Antiplatelets | 24-48 h | 48-72 h |
| Heparin/LMWH | 24 h | 48-72 h |
| Warfarin | 24-48 h | 48-72 h |
| DOACs | 24-48 h | ≥72 h |
📋
Part IV — Pharmacist Checklist
Before Approving:
- Indication (arterial vs venous)
- CrCl calculated (Cockcroft-Gault)
- Platelets <48 h
- INR/aPTT ≤72 h
- Interactions checked
- No duplicate therapy
- Bleeding risk assessed (HAS-BLED, ARC-HBR)
- Duration defined
- Patient counseling documented
🧭
Part V — Decision Flow
Indication
- Arterial → Antiplatelet
- Venous → Anticoagulant
Renal Function
- CrCl ≥30 → DOAC / LMWH
- CrCl <30 → UFH / Warfarin
Bleeding Risk
- High → Shorter DAPT + PPI
- Low-Moderate → Standard duration
🧠
Part VI — Clinical Scenarios
1
Post-PCI ACS + Sepsis, Platelets 70K:
→ Clopidogrel only + PPI
→ Clopidogrel only + PPI
2
AF on Warfarin, NPO for surgery:
→ Hold warfarin 5d → Bridge with enoxaparin → Resume post-op
→ Hold warfarin 5d → Bridge with enoxaparin → Resume post-op
3
DVT on Enoxaparin, CrCl drops to 25:
→ Switch to UFH or reduce to 1 mg/kg daily
→ Switch to UFH or reduce to 1 mg/kg daily
4
ICH + INR 5.2:
→ Vit K 10 mg IV + PCC STAT
→ Vit K 10 mg IV + PCC STAT
5
Post-op DVT prophylaxis:
→ Enoxaparin 40 mg SC after 12-24h
→ Enoxaparin 40 mg SC after 12-24h
6
Mechanical valve + recent stent:
→ Triple ×1 week → Dual ×6 months → Warfarin alone
→ Triple ×1 week → Dual ×6 months → Warfarin alone
🧾
Part VII — Quick Scores
CHA₂DS₂-VASc
≥2 (male) or ≥3 (female) → Anticoagulate
HAS-BLED
≥3 = High bleeding risk → Modify factors (NOT contraindication)
🇪🇬 Egyptian Practical Notes
Drug Availability:
- Ticagrelor often unavailable → Clopidogrel 600 mg load acceptable
- GPIIb/IIIa → Cath lab only
- Use trusted clopidogrel generics
Cost-Effective Choices:
- VTE prophylaxis: Enoxaparin 40 mg
- AF anticoagulation: Apixaban or rivaroxaban (vs warfarin monitoring burden)
- ACS DAPT: Aspirin + clopidogrel (most affordable)
🎓
Key Takeaways
- DAPT duration: 12 months standard, 1-3 months if high bleeding risk
- Apixaban dosing: Reduce to 2.5 mg BID if ≥2 criteria (age ≥80, weight ≤60 kg, Cr ≥1.5)
- Renal adjustment: ALWAYS for LMWH/DOACs
- Warfarin overlap: Minimum 5 days + INR ≥2 × 2 days
- HAS-BLED ≥3: High risk but NOT contraindication—optimize modifiable factors