Effects of an acidic environment on coagulation dynamics

Area of Science:

• Biochemistry
• Hematology
• Trauma Research

Background:

• Traumatic injury can disrupt hydrogen ion homeostasis, leading to acidosis and clinical coagulopathy.
• The precise mechanisms by which blood acidification affects coagulation require further investigation.

Purpose of the Study:

• To investigate the impact of acidified conditions on coagulation dynamics.
• To utilize in vitro models of increasing complexity to assess these effects.

Main Methods:

• Assessed coagulation at pH 7.4 and 7.0 using tissue factor-initiated proteome mixtures and enzyme/inhibitor reactions.
• Monitored thrombin generation and fibrin formation.
• Evaluated clot dynamics in contact pathway-inhibited blood via viscoelastometry.

Main Results:

• Reduced rate constants for antithrombin inhibition of FXa and thrombin by 25-30% at pH 7.0.
• Increased maximum thrombin levels (20%) and diminished clearance rates at pH 7.0.
• Viscoelastic analyses showed altered clot times and maximum clot firmness (MCF), with enhanced MCF in contact pathway-inhibited blood at pH 7.0.

Conclusions:

• Despite decreased procoagulant catalysis at pH 7.0, clot formation is slightly enhanced in ex vivo blood.
• Suppression of thrombin generation is not observed under these conditions.
• Decreased antithrombin reactivity is a potential mechanism explaining these findings.