Novel Anticoagulants Part 2, unique challenges associated with them in the cardiac surgery patient

In this engaging and comprehensive lecture titled "Novel Anticoagulants - Part 2," the focus shifts to understanding the landscape of Direct Oral Anticoagulants (DOACs), which include well-known agents like Pradaxa (dabigatran), Xarelto (rivaroxaban), and Eliquis (apixaban). The lecture covers crucial aspects of anticoagulation therapy, including the properties, clinical implications, and challenges associated with managing patients on these medications.

Introduction to Direct Oral Anticoagulants (DOACs)

DOACs have emerged as popular alternatives to traditional anticoagulants like warfarin due to their predictable pharmacokinetics, rapid onset, and fewer dietary restrictions. However, they also come with their own set of challenges, particularly in managing bleeding complications.

Common 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%).

Understanding DOACs Popularity and Clinical Implications

Warfarin vs. DOACs

• Warfarin (Coumadin):

  • Discovered in the 1920s and historically used as the primary anticoagulant.
  • Requires frequent monitoring (INR), has a long half-life (~40 hours), and unpredictable pharmacokinetics.
  • Reversible with Vitamin K (Phytonadione).

• DOACs:

  • More predictable pharmacokinetics and rapid onset.
  • No routine lab monitoring required.
  • Fewer dietary restrictions.
  • Shorter half-life (e.g., Pradaxa 12-17 hours, Xarelto 5-9 hours).
  • Rapidly gaining popularity over warfarin.

Bleeding Risks and Reversal Strategies

General Bleeding Risks of DOACs

• Pradaxa: Bleeding and gastrointestinal upset.
• Xarelto & Eliquis: Major bleeding, especially gastrointestinal and intracranial.

Reversal Strategies

• Pradaxa (Dabigatran)

  • Reversal Agent: Idarucizumab (Praxbind).
  • Dialyzable due to low protein binding (35%).

• Factor Xa Inhibitors (Xarelto, Eliquis)

  • Reversal Agent: Andexanet alfa (Andexxa).
  • Not dialyzable due to high protein binding (>90%).
  • Use prothrombin complex concentrate (PCC) if Andexanet is unavailable.

Clinical Management and Special Cases

Emergency Management of Bleeding

The lecture provides a detailed plan for managing patients requiring emergency surgery while on DOACs:

• Minor Bleeding (Pradaxa or Factor Xa Inhibitors)

  • Withhold the drug.
  • Monitor clinical status.
  • Recheck coagulation labs.

• Major Bleeding (Pradaxa)

  • Withhold the drug.
  • Administer activated charcoal if the last dose was within a few hours.
  • Administer idarucizumab if available.
  • Prolonged hemodialysis can be considered.

• Major Bleeding (Factor Xa Inhibitors)

  • Withhold the drug.
  • Administer activated charcoal if the last dose was within a few hours.
  • Consider andexanet alfa or PCC.

Platelet Function Testing and Monitoring Coagulation

• Limitations of PT and aPTT:
  • PT and aPTT are not reliable indicators of coagulation status in patients on DOAC therapy due to variability in sensitivity.
  • Thromboelastography (TEG) or Platelet Function Tests: More reliable indicators of hemostatic function.

Case Studies and Anecdotes

Clint Robertson, an experienced perfusionist, joins the lecture to share real-life cases where anticoagulation therapy posed challenges:

1. Case 1: Plavix Overdose and Bleeding

   • Patient presented with massive bleeding post-cardiac surgery due to irreversible platelet inhibition by Plavix.
   • Massive transfusion protocol implemented, including PRBCs, platelets, FFP, and cryoprecipitate.
   • Highlighted the need for better strategies in managing anticoagulant-related bleeding.

2. Case 2: DOACs and Emergency CABG

   • Emergency CABG patient on routine DOAC therapy.
   • Clinicians followed a structured reversal plan, including withholding the drug, activated charcoal, and considering dialysis.

Conclusion: Future of Anticoagulation Management

• The lecture concludes with a discussion on the potential future shifts in anticoagulation therapy.
• Perfusionists and clinicians are encouraged to develop individualized plans and work closely with hematologists and blood bank specialists.
• The importance of patient education regarding DOACs is emphasized, especially given the complexities of reversal strategies.