Anticoagulants

At present, there are three main established anticoagulation medicines used to treat APS: aspirin, heparin and warfarin, one alternative to aspirin called clopidogrel and new direct oral anticoagulants, namely rivaroxaban.

Aspirin

Low dose aspirin 75-150mg daily is usually the first choice of treatment for APS patients who have not had a thrombosis or stroke, and is widely used in pregnancy. It can often help alleviate some of the milder symptoms such as frequent headaches and dizziness.

Since it was discovered in the 1950s that aspirin could make the blood platelets less ‘sticky’, it has been used widely as a preventative medicine to ward off heart attacks and strokes.

The dose of aspirin achieving this effect is tiny, only 75-150mg (a quarter to a half of a normal aspirin tablet) daily. Side effects are rare, but aspirin can cause indigestion, stomach bleeding and some people are allergic to it, particularly asthmatics.

Clopidogrel

There are some patients who cannot tolerate aspirin, particular those with digestive problems and asthmatics. A very useful alternative with similar anti-platelet effects is clopidogrel, which used to have the trade name of Plavix in the UK.

Clopidogrel has a mechanism similar to aspirin in making platelets less ‘sticky’ and a similar dosage is taken – usually 75mg daily.

It does not have the irritant effects on the stomach which can occur with aspirin, neither is it a problem in asthmatics who may prove allergic to aspirin.

Clopidogrel has never been tested during pregnancy so it is advised to switch to aspirin if you are trying for a baby.

One difference between aspirin and clopidogrel is that clopidogrel stays in your system a lot longer than aspirin. Therefore, if you are planning any surgery, do remember to let your healthcare team know that you are taking clopidogrel as they may ask you to switch to another drug about a week before.

Heparin – (Clexane or Fragmin)

Heparin is used as a ‘first line’ treatment for thrombosis in hospitals, and is commonly given to women with obstetric who have suffered previous miscarriages. Daily heparin injections are taken in conjunction with aspirin throughout their pregnancies. It is also sometimes useful in APS patients to alleviate sudden, severe symptoms.

Heparin works in a completely different way to preventative aspirin and has been used extensively in the treatment of thrombosis in the last fifty years.

Given by injection, it is very fast acting and stays in the system for around twelve hours. APS patients usually administer the injection themselves, please read our fact sheet on the best way to do this to avoid bruising.

Side effects such as platelet reduction and osteoporosis, are rarer now that the newer low molecular weight heparin preparations (such as Clexane, Fragmin and Tinzaparin) have largely replaced older types.

Warfarin

Warfarin is taken in tablet form and is an agent that thins the blood and, for most APS patients who have had a thrombosis or stroke, it is currently the treatment of choice. However, it cannot be used in pregnancy as it is potentially dangerous to the unborn baby.

Despite being labelled as ‘rat poison’ because large doses used to be left as bait to kill rats, warfarin is a relatively safe and effective medicine. It has a good long track record having been around since the 1950s.

However, warfarin does react with nearly every environmental factor including a number of drugs such as painkillers, non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics, food containing vitamin K, large amounts of cranberry juice, travelling, stress, and alcohol to name but a few. We discuss warfarin and its interactions in detail in the Living with APS section.

Side effects are rare but the only vital issue is to keep the dosage correct otherwise there is a danger of haemorrhaging – bleeding from over-dosing and hence, over-thinning of the blood.

The dose varies from person to person and no one size fits all – some patients only need 4mg a day while others may need 18mg or more.

The thickness of the blood is measured by a standard clotting test called the INR (International Normalised Ratio). All those taking warfarin have their INR monitored through regular blood tests either by a venous sample or finger prick test carried out in their GP's surgery or anticoagulation clinic or by the patient themselves with an INR self testing machine.

A small minority of patients will be intolerant to warfarin, and have allergic reactions such as skin rashes or their INR will simply not stabilise. Currently, the main alternative to warfarin in the UK is acenocoumarol.

Rivaroxaban

The new direct oral anticoagulant, rivaroxaban (a DOAC), was approved for some APS patient in August 2016 following a multi-centre trial. The London-based Rivaroxaban in APS (RAPS) study found that rivaroxaban could be an effective, safe and convenient alternative to warfarin in some patients with antiphospholipid syndrome.

As the study only investigated patients with APS who had venous blood clots, such as DVTs and PEs, requiring standard intensity warfarin - those with an INR range of between 2.0-3.0 - the results do not apply to other groups of patients such as those who with venous blood clots who have an INR range over 3.0 those with arterial blood clots such as stroke.

Rivaroxaban is taken in tablet form daily, does not need to be monitored at all and only stays in your system around 24 hours.

Update: Direct oral anticoagulants and APS - June 2019

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has issued advice concerning use of direct oral anticoagulants (DOACs) in patients with APS. This advice may result in warfarin being preferred to DOACs for patients with APS until more evidence is available.

The chief aim of drug treatment in patients with APS is to prevent blood clots or strokes. 

The main drug used for many years has been warfarin, which thins the blood. There is good evidence from clinical trials that warfarin is effective in preventing clots in patients with APS.

There are some disadvantages to using warfarin. Patients have to have regular blood tests (called INR tests) to make sure that the level of thinning of the blood is at just the right level – if the dose of warfarin is too high there is an increased risk of bleeding. Furthermore, warfarin interacts with a number of other medications so that when those drugs are being taken the INR tests may need to be done more frequently. 

Due to these issues with warfarin a new generation of blood-thinning drugs has been developed. These drugs are called Direct Oral Anticoagulants or DOACs and examples include rivaroxaban, apixaban and dabigatran. Their effect on blood thinning is more predictable and easier to control, so patients on these drugs do not require regular INR tests. It has also been suggested that these drugs have fewer interactions with other drugs than warfarin does.

The DOACs have been used to prevent clots in a number of other medical conditions and clinical trials have shown that they work as well as warfarin in those conditions. For this reason, some patients with APS have had their treatment changed from warfarin to DOACs.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently issued advice concerning use of DOACs in patients with APS. This advice may result in warfarin being preferred to DOACs for patients with APS until more evidence is available.

A number of medical specialist and patient groups in the UK are currently discussing this advice and we will be posting the outcome of those discussions when it is available. 

In the meantime APS Support UK's advice to patients is as follows:

- If you are taking warfarin, carry on with your treatment as normal. 

- If you are already taking a DOAC do not stop taking it until you have started an alternative blood-thinning agent such as warfarin. Remember that the highest risk of having a clot would be to take no blood-thinning agent at all. Your GP should not stop your DOAC without discussing it with your haematologist and local anticoagulation clinic first. 

- If you are changed from a DOAC to warfarin you will need to start having regular INR blood tests and may need to take heparin injections until the warfarin starts to work and you reach your INR target range.

For more information, please visit the MHRA's website.