What are the clotting factors involved in the intrinsic and extrinsic pathways and what anticoagulants are used in cardiac surgery?

Clotting Factors, Coagulation Pathways, and Anticoagulants in Cardiac Surgery

Clotting Factors

The coagulation cascade consists of sequential conversion of inactive enzymes to active enzymes, ultimately leading to thrombin generation and conversion of soluble fibrinogen to insoluble fibrin 1. The clotting factors include:

• Factor I (Fibrinogen): Converted to fibrin by thrombin; physiological plasma concentration in non-pregnant patients is 2-4 g/L 2
• Factor II (Prothrombin): Vitamin K-dependent; converted to thrombin; half-life of 60 hours 3
• Factor III (Tissue Factor): Initiates extrinsic pathway 2
• Factor IV (Calcium): Essential cofactor for activation of multiple coagulation factors; enables binding of factors to cell membranes 4
• Factor V: Cofactor for Factor X activation
• Factor VII: Vitamin K-dependent; half-life of 4-6 hours 3
• Factor VIII: Cofactor for Factor IX activation
• Factor IX: Vitamin K-dependent; half-life of 24 hours 3
• Factor X: Vitamin K-dependent; half-life of 48-72 hours 3
• Factor XI: Activated by Factor XIIa and thrombin
• Factor XII (Hageman Factor): Initiates intrinsic pathway
• Factor XIII: Cross-links fibrin to improve clot strength 2
• Protein C: Vitamin K-dependent; anticoagulant protein; half-life of 8 hours 3
• Protein S: Vitamin K-dependent; anticoagulant protein; half-life of 30 hours 3

Coagulation Pathways

Extrinsic Pathway

• Initiation: Begins with tissue factor (Factor III) exposure following tissue injury 2
• Key Steps:
  • Tissue factor binds to Factor VII, activating it to VIIa
  • Factor VIIa/tissue factor complex activates Factor X to Xa
  • Factor Xa converts prothrombin (II) to thrombin (IIa) 2
• Function: Provides rapid initial response to injury 1

Intrinsic Pathway

• Initiation: Begins with contact activation of Factor XII on negatively charged surfaces 2
• Key Steps:
  • Activated Factor XII (XIIa) activates Factor XI to XIa
  • Factor XIa activates Factor IX to IXa
  • Factor IXa forms complex with Factor VIIIa to activate Factor X to Xa
  • Factor Xa converts prothrombin to thrombin 2
• Function: Provides sustained thrombin generation 1

Common Pathway

• Both pathways converge at Factor X activation 5
• Factor Xa, along with Factor Va, converts prothrombin to thrombin
• Thrombin cleaves fibrinopeptides from fibrinogen to form fibrin monomers
• Factor XIII cross-links fibrin for clot stability 2

Anticoagulants Used in Cardiac Surgery

Unfractionated Heparin (UFH)

• Primary anticoagulant used during cardiopulmonary bypass (CPB) 2
• Mechanism: Binds to antithrombin, potentiating inactivation of thrombin and Factor Xa by up to 1000-fold 2
• Dosing: 300-500 U/kg initial dose before CPB 2
• Monitoring: Activated clotting time (ACT) with target values ranging from 300-600 seconds during CPB 2
• Reversal: Protamine sulfate 2

Low Molecular Weight Heparins (LMWH)

• Less commonly used in cardiac surgery due to longer half-life and incomplete reversal with protamine 2
• More predictable pharmacokinetics than UFH 6

Direct Oral Anticoagulants (DOACs)

• Should be discontinued before cardiac surgery due to bleeding risk 2
• No specific reversal agents available for all DOACs for use during cardiac surgery 6

Warfarin

• Mechanism: Inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins C and S 3
• Used for: Long-term anticoagulation after cardiac surgery, particularly for patients with mechanical heart valves or atrial fibrillation 2
• Monitoring: International Normalized Ratio (INR) 2
• Reversal: Vitamin K, fresh frozen plasma, or prothrombin complex concentrate 3

Antifibrinolytics

• Tranexamic acid: Commonly used in cardiac surgery to reduce blood loss 2
• Dosing: Variable dosing protocols are used in clinical practice 2
• Benefits: Reduces perioperative bleeding and transfusion requirements 6

Management of Anticoagulation During Cardiac Surgery

Pre-CPB Phase

• Initial heparin dose: 300-500 U/kg to achieve target ACT 2
• ACT target: Most centers aim for >480 seconds, though lower targets (250-300 seconds) may be safe with heparin-coated circuits 2

During CPB

• Monitoring: Regular ACT measurements with additional heparin doses given if ACT decreases 2
• Individualized heparin management: Systems like Hepcon Haemostasis Management System may be used to optimize dosing 2

Post-CPB Phase

• Heparin reversal: Protamine sulfate administration 2
• Monitoring for heparin rebound: May contribute to postoperative bleeding 2
• Management of coagulopathy: May require blood products or factor concentrates 2

Special Considerations

• Heparin resistance: Occurs in approximately 17.5% of cardiac surgery patients 2
• Management options: Additional heparin, fresh frozen plasma, or antithrombin concentrate 2
• Monitoring limitations: ACT values do not linearly correlate with plasma heparin concentrations during CPB due to factors like hemodilution, hypothermia, and platelet dysfunction 2

In cardiac surgery, unfractionated heparin remains the primary anticoagulant with monitoring via activated clotting time, while tranexamic acid is commonly used to reduce bleeding risk. 2