Novel Anticoagulants - Hemostasis Post Cardiopulmonary Bypass

"Novel Anticoagulants - Hemostasis Post Cardiopulmonary Bypass" is a comprehensive and engaging webinar that delves into the intricacies of managing hemostasis in cardiac surgery patients, specifically focusing on the use of Direct Oral Anticoagulants (DOACs) and other novel anticoagulants. The lecture explores the challenges associated with anticoagulation therapy during and after cardiopulmonary bypass (CPB), offering valuable insights into effective strategies and clinical management.

Understanding Direct Oral Anticoagulants (DOACs)

Direct Oral Anticoagulants have become increasingly popular due to their predictable pharmacokinetics, rapid onset, and fewer dietary restrictions compared to traditional anticoagulants like warfarin.

Key DOACs and Their Mechanisms

1. Pradaxa (Dabigatran)

   • Mechanism: Direct thrombin (Factor IIa) inhibitor.
   • Indications: Stroke prevention in atrial fibrillation (AF), treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
   • Dosage and Frequency: Taken twice daily.
   • Adverse Effects: Bleeding, gastrointestinal upset.
   • Special Properties: Pro-drug, bioavailability of 3-7%, predominantly renally excreted (80%).

2. Xarelto (Rivaroxaban)

   • Mechanism: Factor Xa inhibitor.
   • Indications: Stroke prevention in AF, DVT, PE treatment.
   • Dosage and Frequency: Once or twice daily.
   • Adverse Effects: Bleeding.
   • Special Properties: High bioavailability (66-100%), moderate renal excretion (36%).

3. Eliquis (Apixaban)

   • Mechanism: Factor Xa inhibitor.
   • Indications: Stroke prevention in AF, DVT, PE treatment.
   • Dosage and Frequency: Twice daily.
   • Adverse Effects: Bleeding.
   • Special Properties: Moderate bioavailability (~50%), low renal excretion (27%).

Clinical Case Study: Urgent CABG Surgery Post-Anticoagulation

The presenter begins with a challenging clinical case involving a 68-year-old male admitted to the emergency department (ED) with chest pain. After being given 300 to 900 mg of Plavix (clopidogrel) for planned stenting, a coronary angiogram revealed multiple high-grade lesions requiring urgent coronary artery bypass graft (CABG) surgery. Complicating the case further was a depleted blood bank and the irreversible platelet inhibition of Plavix.

Key Questions Raised:

• What strategies can be employed to manage bleeding effectively during emergency surgery?
• How does Plavix's irreversible platelet inhibition impact perioperative management?

Management Strategies for Platelet Inhibition

• Integrilin (Eptifibatide): A reversible glycoprotein IIb/IIIa inhibitor with a short half-life of 2.5 hours.
• Platelet Transfusion: A crucial strategy, although challenging due to high cytokine load.

Novel Platelet Inhibitors:

• Aspirin, Persantine (Dipyridamole), Ticlid (Ticlopidine): Traditional inhibitors.
• Plavix (Clopidogrel), Integrilin (Eptifibatide), Brilinta (Ticagrelor), Effient (Prasugrel): Newer generation inhibitors.

Impact of Diet on Platelet Function

The lecture introduces fascinating research on the influence of diet and nutrients on platelet function:

• Dark Chocolate: Reduces platelet aggregation via 2b/3a receptor modulation.
• Garlic & Onion: Improve postprandial flow-mediated vasodilation.
• Red Wine: Reduces plasma fibrinogen levels and inhibits platelet aggregation.
• White Wine: Inhibits ADP-induced aggregation.

Coagulation Pathways and Factor Inhibition

A thorough review of intrinsic and extrinsic coagulation pathways helps frame the role of various anticoagulants:

• Vitamin K Antagonists (Warfarin): Inhibit factors II, VII, IX, and X.
• Direct Thrombin Inhibitors (Pradaxa): Inhibit Factor IIa.
• Factor Xa Inhibitors (Xarelto, Eliquis): Inhibit Factor Xa.

Calculating Half-Life and Therapeutic Implications

The importance of understanding drug half-life in managing anticoagulants is emphasized:

• Example Calculation 1: If a drug has a half-life of two hours and the initial concentration is 1200 mg/L, the concentration will be 75 mg/L after eight hours.
• Example Calculation 2: If a drug has a half-life of three hours and the initial concentration is 3600 mg/L, the concentration will be 375 mg/L after ten hours.

Hemostasis Management Post-Cardiopulmonary Bypass

Challenges with DOACs

• Prolonged Half-Life: Requires precise calculation for timing surgeries.
• Irreversible Inhibition: Limited reversal agents necessitate careful planning.

Practical Hemostasis Strategies

• Reversal Agents: Idarucizumab for Pradaxa, Andexanet alfa for Factor Xa inhibitors.
• Prothrombin Complex Concentrate (PCC): Three- or four-factor concentrates.
• Dialysis & Ultrafiltration: Effective for renally excreted drugs like Pradaxa.

Conclusion

"Novel Anticoagulants - Hemostasis Post Cardiopulmonary Bypass" provides a valuable framework for clinicians to navigate the challenges of anticoagulation therapy. From practical case studies to diet considerations and detailed coagulation pathways, the lecture equips perfusionists and cardiac surgeons with essential knowledge for managing bleeding risks associated with novel anticoagulants.