Anticoagulants

Anticoagulants are medicines that increase the time it takes for blood to clot. They are commonly called blood thinners. 

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.

What are anticoagulants used for?

Anticoagulants may be used to treat blood clots, or in conditions where the risk of blood clots is increased to reduce the risk. Examples of conditions where anticoagulants may be used include:

• Atrial fibrillation
• Deep vein thrombosis (DVT)
• Hip or knee replacement surgery
• Ischemic stroke
• Myocardial infarction (heart attack)
• Pulmonary embolism
• Unstable angina.

What are the differences between anticoagulants?

Anticoagulants may be divided into four main groups: coumarins and indandiones; factor Xa inhibitors; heparins; and direct thrombin inhibitors.

Coumarins and indandiones

Warfarin is a coumarin, and the only coumarin available in the U.S for human use. It works by limiting the availability of vitamin K, a vitamin that is necessary for the blood coagulation pathway to produce clotting factors II, VII, IX, and X. This decreases the blood’s ability to clot.

Indandiones have a similar way of working to coumarins but they are mainly used for pest control to control rat, mice, and rabbit populations. Examples include pindone and diphacinone.

Coumarins and indandiones may also be called vitamin K antagonists.

Factor Xa inhibitors

Factor Xa inhibitors work on factor Xa in the coagulation cascade, which is responsible for converting the protein prothrombin into thrombin. Factor Xa inhibitors can affect factor Xa within the blood and also within a pre-existing clot.

Factor Xa inhibitors do not require routine monitoring, unlike some other anticoagulants.

Heparins

The heparins are a group of anticoagulants that consist of unfractionated heparin, low molecular weight heparins, and heparinoids.

Unfractionated heparin (usually just called heparin) needs to be given directly into the blood by intravenous (IV) injection, and inhibits thrombin and factor Xa, factors necessary in the final stages of the blood clotting cascade. Heparin may also be called high molecular weight heparin. Daily monitoring is required with heparin to check the aPTT. The aPTT is the speed at which clotting occurs.

Low molecular weight heparins (LMWH) also work on thrombin and factor Xa; however, they preferentially inactivate factor Xa. Because their anticoagulant response is more predictable, they do not need daily blood monitoring. LMWHs last much longer in the body than heparin and are injected under the skin (subcutaneously). Some people can learn to inject LMWHs at home by themselves.

Heparinoids have a similar action to heparin and are extracted from specific animal and plant tissues or made synthetically. They are usually applied topically and are easily absorbed into the skin where they can reduce small blood clots, reduce inflammation and associated pain and discomfort. Chitin and chondroitin sulfate are also heparinoids.

Direct thrombin inhibitors

Direct thrombin inhibitors bind directly to thrombin, inhibiting its action. Direct thrombin inhibitors that need to be given by injection include desirudin which binds to both the active enzymatic site and to exosite 1, and argatroban which binds to the active enzymatic site only. Dabigatran is an oral direct thrombin inhibitor which binds reversibly to the active enzymatic site.

Are anticoagulants safe?

Anticoagulants are considered safe when administered exactly as intended for the recommended duration of time. However, they have been associated with some serious side effects such as:

• Major or fatal bleeding and haemorrhage: Because of the way they work to prolong bleeding time, there is always a risk of severe bleeding with anticoagulants, particularly in people with risk factors such as active ulceration, bleeding disorders, hemorrhagic stroke, following certain types of surgery, with kidney disease, or in people taking medicines that also increase the risk of bleeding. Any bleeding that does not stop or other signs such as persistent nosebleeds, blood in the urine or stools, heavy menstrual bleeding, or coughing up blood should be investigated further.
• Spinal/epidural hematomas: Risk is higher with LMWHs when administered to people undergoing neuraxial (spinal or epidural) anesthesia or spinal puncture. These hematomas may result in permanent paralysis
• Thrombocytopenia (a deficiency of platelets in the blood)
• Necrosis and/or gangrene of the skin: rare, but has been associated with warfarin use
• An increased risk of thrombotic events on premature discontinuation of dabigatran (before completion of a course of therapy).

Warfarin can also interact with certain foods and many commonly used medicines. Regular blood monitoring (international normalized ratio-INR) is necessary because there is a fine line between an effective dose and a toxic one.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the side effects of anticoagulants?

The more common side effects that have been associated with anticoagulants include:

• Bleeding
• Gastrointestinal effects such as diarrhea, heartburn, nausea, and loss of appetite
• Irritation and pain around the site of injection (injectable anticoagulants only)
• Elevations in liver enzymes
• Shortness of breath.

For a complete list of side effects, please refer to the individual drug monographs.