Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass

Area of Science:

• Cardiovascular Surgery
• Hematology
• Coagulation Science

Background:

• Antithrombin (AT) levels decline during cardiopulmonary bypass (CPB), especially with deep hypothermic circulatory arrest (DHCA).
• Low AT levels can disrupt the balance of pro- and anticoagulant factors, potentially leading to thrombosis.

Purpose of the Study:

• To investigate the impact of reduced antithrombin levels on thrombin generation post-CPB with DHCA.
• To assess whether supplementing plasma with antithrombin can mitigate excessive thrombin generation in this setting.

Main Methods:

• Collected blood samples from five cardiac surgery patients undergoing CPB with DHCA before and after the procedure.
• Measured antithrombin levels and evaluated thrombin generation using the Thrombinoscope system.
• Manipulated plasma AT levels by adding normal donor plasma, AT-deficient plasma, or purified AT.

Main Results:

• AT levels significantly decreased after CPB with DHCA (37% of normal activity).
• Plasma from post-CPB patients showed increased peak thrombin generation when supplemented with AT-deficient plasma (117 nM).
• Addition of purified AT to post-CPB plasma markedly reduced peak thrombin generation (12.2 nM).

Conclusions:

• Severe reduction in plasma AT activity occurs after CPB with DHCA.
• Administering coagulation factors without AT repletion may result in excessive thrombin generation.
• This excessive thrombin generation could clinically lead to a hypercoagulable state.