History

The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-activity based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's may be identified by High-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, such as unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e. : argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).

Mechanism of action 

How do they work?

Your body is constantly balancing clotting and anti-clotting processes. If your blood doesn't clot enough, an injury can cause severe blood loss or even death. If it clots too much, it can cause the dangerous medical events mentioned above. Certain blood components keep your clotting processes in an inactive state. That way, your body can activate them quickly when you have an injury that needs repair.

Thanks to that balancing act, clotting is usually a helpful process. It stops bleeding, creates a protective covering to keep germs and debris out of a wound, and then rebuilds the skin so it’s good as new (or nearly so, if the wound leaves a scar).

Anticoagulants work by interfering with the normal clotting processes. Just like their name suggests, they prevent or undo coagulation, the process where your blood solidifies to form a clot. Depending on the type of anticoagulant, the clotting process disruption happens in different ways.

•IV and injectable medications

Heparin and its derivatives:

Heparin is a medication that inhibits clotting by activating your body's anti-clotting processes. One of the anticlotting processes uses a type of blood protein called antithrombin. Heparin works by activating antithrombin, and then antithrombin keeps other parts of the clotting process from working normally.

Heparin comes in two different types, and there is a third medication that is closely related:

•Unfractionated heparin (UFH). Unfractionated heparin is stronger and fast-acting. This is because UFH has a longer molecule, which means it’s long enough to help wrap around both antithrombin and thrombin, a protein that promotes clotting, holding them together. This neutralizes both proteins, further preventing clotting. UFH also needs constant monitoring with lab tests. That’s because its effectiveness depends on its dosage, and the needed dosage can be very different from person to person. Too little won't do enough to prevent clotting, and too much will create a risk of bleeding.

•Low-molecular-weight heparin (LMWH). Low-molecular-weight heparin has shorter molecules, which means it can only attach to antithrombin. This also means the effects are longer-lasting, more predictable and LMWH doesn’t need the close monitoring required with UFH.

•Fondaparinux. Fondaparinux is a synthetic medication that works similarly to heparin. Like heparin, fondaparinux activates antithrombin but acts over a much longer period. However, it’s not as strong as UFH or LMWH, so it’s most often used to prevent clots rather than treat clotting problems that are already happening (unless given along with other medications).

•Direct thrombin inhibitors:

Thrombin inhibitors work by attaching to thrombin, keeping it from assisting clotting processes. They are often used as alternatives to heparin and its variants, especially to prevent the formation of clots after certain medical procedures. These include argatroban, desirudin and bivalirudin.

•Oral medications

Warfarin (vitamin K antagonist)

Warfarin is a vitamin K antagonist, meaning it blocks the use of vitamin K — a key ingredient in the clotting process. However, a major drawback of warfarin is that it needs careful dosing and regular lab testing to prevent complications. When the dosage isn’t precise enough, it can lead to severe bleeding.

•In some cases, certain conditions mean that warfarin is the only anticoagulant that you can take. These include:

•Diseases affecting the mitral valve of your heart.

•Having a mechanical heart valve.

•End-stage kidney disease.

•Direct oral anticoagulants

These medications can all be taken regularly without regular lab testing and are often used when warfarin isn’t an option. One medication, dabigatran, is a thrombin inhibitor similar to the IV thrombin inhibitors listed earlier. Other medications, apixaban, edoxaban and betrixaban, are all inhibitors of factor Xa (10-A), a key clotting component.

How to administer the dose?

Your doctor or nurse should tell you how much of your anticoagulant medicine to take and when to take it

If you're unsure how to take your medicine, check the patient information leaflet that comes with it or ask your anticoagulant clinic, GP or pharmacist what to do.

As for the dose of your anticoagulants. 

For most people, anticoagulant tablets or capsules should be taken at the same time once or twice a day. It's important to take your medicine as scheduled because the effect of some anticoagulants can start to wear off within a day.

Warfarin, apixaban (Eliquis) and dabigatran (Pradaxa) should be taken with water. Edoxaban (Lixiana) can be taken with or without food. Rivaroxaban (Xarelto) is normally taken with food.

Depending on your dose, you may need to take more than one tablet or capsule at a time.

Warfarin tablets come in different colours (white, brown, blue and pink) to indicate their strength. You may need to take a combination of different coloured tablets to reach your total dose. Other anticoagulants come in different strengths and colours.

Your doctor or nurse will explain how many tablets you need to take, when to take them, and what the different colours mean.

https://www.nhs.uk/conditions/anticoagulants/dosage/ 

Types Of Anticoagulants. 

There are several different types of anticoagulant. Each type works at a different level on the blood coagulation pathway. Some can be given by mouth; others can only be given by injection.

•IV and injectable medications Heparin and its derivatives.

•Direct thrombin inhibitors

•Oral medications

Warfarin (vitamin K antagonist)

Enoxparin 

Fondaparinux 

Rivaroxaban 

Apixaban