How Does the Anticoagulant Citrate Work?

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What is Coagulation?

Coagulation is a series of chemical reactions that allow blood to form clots, which helps organisms to repair damaged blood vessel walls. First, platelets are activated after the damage to the walls of the blood vessel causes a reaction that binds subendothelium proteins like collagen to bind with glycoprotein. When the platelets are activated, they release stored granules into the plasma of the blood which include serotonin, ADP, vWF, platelet factor 4, platelet-activating factor (PAF) and thromboxane A2 (TXA2). The contents of these granules activate other platelets and they begin a protein receptor cascade causing an increased calcium concentration in the cytosol of the platelets. This calcium will be a major factor in the use of the anticoagulant citrate. Calcium activates a series of proteins that in turn activate an increased ability of the glycoprotein to bind fibrinogen. Platelets begin coming together. A series of reactions begin as the two phases of the coagulation cascade occur, the contact activation pathway and the tissue factor pathway. This is where thrombin and coagulation factors come into play and many coagulation reactions occur.


There are certain substances that are needed to ensure that the coagulation cascade works as planned. From an anticoagulation standpoint, calcium is one of the most important. Calcium is needed at multiple points at the coagulation cascade. Calcium's most integral role, though, is to regulate the binding of the complexes during the reaction via terminal gamma-carboxy residues on FXa and FIXa to phospholipid surfaces expressed by platelets in addition to the procoagulant microvesicles or microparticles shed from them. There are other important co-factors like Vitamin K for instance, and without calcium and those other co-factors, coagulation will not occur properly.

Citrate and EDTA

Citrate, in the form of sodium citrate or acid-citrate-dextrose, is used to disrupt the coagulation cascade and prevent clotting. These citrate compounds bind to the calcium in the blood. By reducing the amount of calcium, there will be no regulation of the binding and the cascade cannot begin. Citrate is often skipped over, as many doctors are more prone to using EDTA or ethylenediaminetetraacetic acid as it tends to bind calcium more strongly and irreversibly. These anticoagulants are used in test tubes, medical and surgical equipment, and laboratory instruments in order to keep blood from clotting and becoming unusable for medical purposes.