What is the mechanism of action of calcium citrate in preventing coagulation in autologous blood collection for transfusion?

Mechanism of Action of Calcium Citrate in Preventing Coagulation

The most likely mechanism of action of calcium citrate in preventing coagulation during autologous blood collection is to chelate calcium ions, which are essential cofactors in the coagulation cascade (answer D). 1

Role of Calcium in Coagulation

• Calcium ions (Ca²⁺) are essential cofactors in the activation of multiple coagulation factors, including factors II, VII, IX, and X, as well as proteins C and S 1
• Calcium enables the binding of coagulation factors to cell membranes and extracellular vesicles, which is a prerequisite for thrombin formation 2
• Calcium is necessary for fibrin polymerization and stabilization during clot formation 1
• Calcium is required for platelet adhesion at sites of vessel injury 1

Mechanism of Calcium Citrate as an Anticoagulant

• Calcium citrate functions as an anticoagulant by chelating (binding) ionized calcium in the blood, thereby preventing the calcium-dependent steps in the coagulation cascade 2
• By reducing the available ionized calcium concentration, citrate prevents the progression of the coagulation cascade and subsequent clot formation 3
• This chelation mechanism is different from other anticoagulants such as:
  • Hirudin, which directly inhibits thrombin 2
  • Heparin, which indirectly inhibits thrombin by binding to anti-thrombin 2
  • Factor Xa inhibitors, which block a specific coagulation factor 1

Clinical Applications

• Citrate is commonly used as an anticoagulant in blood collection tubes and blood products to maintain sample stability 4
• In autologous blood collection, calcium citrate prevents coagulation while the blood is stored, allowing it to remain viable for later transfusion 4
• The anticoagulant effect is reversible - when citrated blood is transfused back to the patient, the patient's metabolism processes the citrate, releasing the bound calcium and allowing normal coagulation to resume 3

Important Considerations

• Excessive citrate load during massive transfusions can lead to hypocalcemia in the recipient due to the chelation of the patient's calcium 5
• Hypocalcemia from citrate toxicity is more pronounced in patients with liver dysfunction, hypothermia, or hypoperfusion due to impaired citrate metabolism 5
• Ionized calcium levels should be monitored during massive transfusions to prevent complications of hypocalcemia, which include coagulopathy, cardiac dysrhythmias, and cardiovascular dysfunction 5
• The anticoagulant effect of citrate is not through inhibition of factor Xa, enhancement of fibrinolysis, or inhibition of platelet aggregation, though hypocalcemia can secondarily affect platelet function 1, 3