Anticoagulants and dentistry
Anticoagulant mechanisms
Clots are made mainly of the protein fibrin, and platelets. Fibrin is the end result of a very complicated cascade of biochemical reactions that are normally initiated when there is tissue injury.
Clotting in pooled blood starts when a compound called Platelet Tissue Factor (TF, or Factor III) initiates a cascade of biochemical reactions involving many chemicals. TF is found in the lining of blood vessels, and in some white blood cells.
- Prothrombin and fibrinogen are inactive proteins naturally present in the blood.
- Prothrombin is turned into thrombin by clotting factors created during the clotting cascade. This conversion needs vitamin K to be present.
- Thrombin causes fibrinogen to convert into fibrin.
- Fibrin, the final component in the pathway is the main component of a clot (along with platelets)
Blood pooling allows the accumulation and concentration of clotting factors like TF and thrombin.
Anticoagulants work by interrupting the clotting pathway. Different anticoagulant drugs block different parts of the cascade.
Modes of action
Vitamin K antagonists
Vitamin K antagonists like Warfarin have been around since 1954.
Vitamin K is required for the proper production of certain proteins involved in the blood clotting process. For example, it is needed (along with other factors) to help change prothrombin into a shape that can create thrombin.
Vitamin K antagonists are a group of substances that reduce blood clotting by reducing the action of vitamin K.
DOACs (Direct Oral Anticoagulants)
Factor Xa is a clotting factor at a very important turn in the coagulation pathway leading to thrombin generation and subsequent clot formation.
DOACs are factor Xa inhibitors. They prevent Factor Xa from working by binding to it. Inhibition of Factor Xa results in a reduction of the thrombin “burst” during the coagulation cascade. This lack of thrombin means fibrinogen can not be converted to fibrin strands and so prevents clot formation
DOACs are also called NOACs (Novel Oral Anticoagulants), but they have been around since 2010, so they are no longer “novel”.
Heparin and LMWH’s
Low molecular weight heparins are an Antithrombin activator. Antithrombin III is a natural protein that is normally inactive. Heparin activates it by changing its shape.
Activated Antithrombin prevents the formation of other clotting factors, like thrombin, and Factor Xa. Thus, thrombin cannot convert fibrinogen to fibrin strands and so prevents clot formation
Heparin was discovered in 1916, but did not enter clinical trials until 1935. It is injected subcutaneously, not taken orally.