Anticoagulants

Anticoagulants: What are they?

Anticoagulants are drugs which prevent the blood from forming clots so easily – some people describe this as ‘thinning’ the blood although this isn’t technically correct. There are several widely-used anticoagulant drugs (see below).

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Why are anticoagulants needed ?

Blood clotting, the mechanism by which the blood sticks together to form small solid clots is a natural and vital function of the body. The blood has a complex system which regulates when or how clots form. More than 30 substances in the blood are known to affect clotting and it's essential that the balance of these clotting factors is right.
Blood coagulation is triggered by blood cells called platelets which, through a series of chemical reactions, produce a substance called thrombin. This converts a blood protein fibrinogen to fibrin which then create a series of tiny threads which lead the plasma in the blood to become sticky. The process protects the body from excessive bleeding, ensuring that a clot forms at the site of a wound or injury - either inside or outside the body. There is a constant state of formation and breakdown of tiny clots throughout the body.
In some conditions some of the clotting chemicals are deficient or not working as they should, and the blood doesn’t form clots properly and there is a risk of haemorrhage.
Alternatively variation in the levels of clotting factors can make the blood form clots too easily and there is a risk of clots forming where or when they are not wanted, leading to life-threatening conditions such as strokes and heart attacks. Other conditions such as abnormal heart rhythms or operations can trigger normal blood to clot leading to complications. In these cases anticoagulant drugs can help to prevent clot formation.

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When are anticoagulants used?

Anticoagulant drugs are prescribed to people who are known to be at risk of blood clots, including:

• People with artificial heart valves (mechanical valves have a high risk of triggering blood clots and anyone with a mechanical valve usually needs to take anticoagulant drugs for life. Biological valves made of animal tissue do not have this risk or require anticoagulants.)
• Those who have had a heart attack. Heart attacks are caused by a thrombosis or clot in the coronary arteries. Anticoagulants can help reduce the damage and risk of further problems.
• People who have had a stroke. In those types of stroke caused by a thrombosis or clot, anticoagulants can help reduce the risk of damage and further problems. Some strokes are the result of a haemorrhage or bleed, and anticoagulants must not be given.
• Those who have had or are at risk of deep vein thrombosis (DVT) or pulmonary embolus (PE) Anticoagulants may need to be taken for several months after a DVT or PE.
• People suffering from atrial fibrillation. In this common heart arrhythmia, the irregular inefficient contractions of the upper chambers of the heart can lead to the formation of clots which may then pass up to the brain and cause a stroke.
• Patients undergoing orthopaedic surgery. After any surgery the blood becomes more sticky and likely to form clots for a while. In addition, surgery which leaves a person temporarily less mobile increases the risk of a DVT.
• People with angina which is a sign of narrowing of the coronary arteries and an increased risk of coronary thrombosis. Anticoagulants help to keep the blood flowing smoothly.
• People undergoing procedures to coronary arteries, for example stent insertion

One of the most commonly used anticoagulants is aspirin. The blood's natural anti-clotting substance, heparin, is given by injection, while warfarin is the most widely prescribed anticoagulant taken orally.

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Teatment with anticoagulants

There are a number of treatments currently being prescribed:

Aspirin

As well as its pain-relieving properties, aspirin is increasingly used to help thin the blood. It works by its action on the platelets – aspirin prevents platelets from clumping together and starting the formation of a clot, and is known as an anti-platelet agent.
People who have suffered a heart attack or stroke are given powerful clot-dissolving drugs (also known as thrombolytics or 'clot-buster therapy') immediately to break down the blockage of the blood vessels and improve blood flow. They will then generally be prescribed long term anticoagulant drugs to prevent further problems. Taking low doses of aspirin daily is one of the cheapest and most effective means of preventing a further attack but has been shown to have a significant risk of gastric bleeding if taken long term in the absence of previous heart problems or stroke (other medicines such as some called proton pump inhibitors or PPIs may be recommended to reduce this risk.)
In the UK 300,000 people suffer from a heart attack every year and the vast majority will be prescribed low dose aspirin afterwards to try to make platelets in the blood less sticky and prevent a second attack. Many of the 1.4 million angina sufferers in the UK are also prescribed low-dose aspirin.
Aspirin has also been recommended for those embarking on long haul flights because of the increased risk of a clot forming in the leg during periods of prolonged inactivity.

Heparin

Heparin was first discovered in 1916. It's found naturally in many cells in the body. Heparin comes in two main forms and is routinely given intravenously after a clot has been diagnosed. The two forms act in a slightly different way on the thrombin in the blood and have the effect of prolonging the time a clot takes to form.
The newer form, low molecular weight heparin, has been associated with fewer bleeding complications compared to unfractionated heparin. It can be administered either by drip or injection under the skin. For immediate effect, such as after a DVT or a pulmonary embolism, an intravenous dose is given to ensure it's more rapidly delivered to the blood stream.
It has been shown that in general most patients in hospital are at increased risk of DVTs and PEs, because of factors such as being immobile. For that reason, most patients are offered a daily subcutaneous injection of a low dose of low molecular weight heparin to protect them until they are active again.
The effects of heparin on clotting can be measured with a test called APTT and, as with warfarin, the dose needs to be adjusted to make sure it's at the right therapeutic level. The common APTT ratio is between 1.5 and 2.5.

Warfarin

Warfarin is an anticoagulant taken in tablet form. It acts by interfering with vitamin K which is vital for blood clotting and the manufacture of prothrombin in the body.
Warfarin is the drug usually given when people require significant long term anticoagulation, as it offers more protection than aspirin in many conditions such as atrial fibrillation or DVT.
Patients who have undergone major heart surgery, including valve replacement and heart bypass surgery will generally take this anticoagulant to avoid the chance of a clot forming around the new valve or artery. Patients will be generally be given heparin for several days followed by three to six months of warfarin.
One of the problems with warfarin is that patients taking this long term anticoagulant therapy need to have their blood checked regularly to make sure they are on the right dose. They may need to frequently adjust the dose to keep the blood at a stable level of anticoagulation as many other drugs, conditions and even alcohol and certain foods can interfere with the activity of warfarin. For example, a diet high in vitamin K which is found in leafy green vegetables may inhibit some of the warfarin effect.
People taking warfarin need to be aware of these potential interactions.

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New anticoagulants

Several new oral anticoagulant drugs such as dabigatran and rivaroxaban are being introduced which have the advantage of providing a stable level of anticoagulation on a regular dose which doesn’t require such constant monitoring and adjustment as warfarin.
However it may be some time before these are widely available as they are likely to be much more expensive tablet for tablet, although there are cost savings in terms of blood testing and monitoring of anticoagulation levels.

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Measuring effects

Warfarin slows the time blood takes to clot. This anticoagulant effect can be measured by a test called the international normalised ratio or INR, a measurement adopted by the World Health Organisation. The desired INR range is usually between 2.0 - 3.0 (but may be higher, for example when used for patients with mechanical heart valves). This is calculated by measuring the patient's actual prothrombin or clotting time against an expected or control time
The individual response to warfarin varies so it's important that INR measurements are closely monitored. Usually the INR will be measured with a daily blood test when a patient is first prescribed warfarin until doctors are sure the clotting time is within a safe range. This will then be reduced to two or three times a week, then weekly and eventually monthly or even quarterly for those who are stable and not taking other medications.

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What are the risks?

The main side-effect of taking anticoagulants is increased likelihood of bleeding - particularly if the INR is above the desired level. The risk of bleeding with warfarin increases in people aged over 65 and those with a history of stroke or gastrointestinal bleeding. With aspirin the main complication is gastrointestinal bleeding because of damage to the stomach lining.
Low dose aspirin pills (75mg) are usually given an enteric coating which protects the stomach tissue. Newer antiplatelet drugs such as clopidogrel may be used instead of aspirin, for example after a heart attack or for preventing a stroke.
One very rare warfarin side-effect is skin necrosis, which usually becomes apparent within a week of starting treatment. Lesions appear on the skin which are due to small clots in the blood vessels under the surface.
Combined treatment with warfarin and aspirin has been recommend in the UK for prevention of heart attacks in people at risk though this may increase the risk of a haemorrhage.
Heparin's side effects also include osteoporosis, hair loss and hypersensitivity.
Warfarin should be avoided in pregnancy because it crosses the placenta to the baby, though use of heparin in pregnancy is safe. Warfarin can also interact with other drugs, including some antibiotics, barbiturates and alcohol so it's essential that patients discuss any medications with their doctor.