Anticoagulant Therapy During Pregnancy

Overview

Anticoagulation therapy involves the use of medications called anticoagulants to prevent the formation of blood clots. This is done by either helping your body to break down existing clots or by preventing the formation of new clots. Anticoagulants are important to treat and prevent many potentially life-threatening conditions resulting from blood clots, such as strokes, heart attacks, and pulmonary embolisms.

Anticoagulation therapy is also an important consideration in pregnancy. Pregnancy involves various hormonal and physiological changes in your body to support your growing baby. While crucial for a healthy pregnancy and foetal development, these changes can also lead to an increased risk of thrombosis (the formation of blood clots in your blood vessels or heart) for the mother.¹

Pregnancy is associated with a 5-fold increase in the risk of venous thromboembolism (VTE), and this risk can persist until nearly 12 weeks postpartum (after birth). VTE is a condition where a blood clot forms in a vein including deep vein thrombosis (DVT) - where a clot forms in the deep veins of your legs, arms, or pelvis - and pulmonary embolism - where a clot forms in your lungs. A VTE can block blood flow and cause serious complications, with pulmonary embolism remaining the leading cause of maternal mortality.² Therefore, anticoagulant therapy can be important during pregnancy to reduce this risk of blood clots and protect both the mother and the developing foetus.

However, there are many complications presented with pregnancies, and the use of specific anticoagulant therapies during pregnancies involves a balance between the risks and benefits to both the mother and foetus.

How does anticoagulation therapy work?

A blood clot is a tangle of blood cells which clump together to form a semi-solid state. This clotting process is important to prevent yourself from losing blood, for example, if you cut yourself. Normally, your body balances clotting and anti-clotting processes to keep you healthy.³

Anticoagulation therapy works by interfering with the normal clotting processes to prevent or stop coagulation (the process where your blood solidifies to form a clot) in people at high risk of having blood clots. Different anticoagulation medications work in different ways to stop this from happening:⁴

Heparin

Heparin is a medication that prevents current clots from growing larger and new clots from forming by activating your body's natural anti-clotting processes. Heparin comes in two different forms:

• Unfractionated heparin (UFH): This medication is strong and fast-acting to rapidly prevent clot formation, but requires frequent blood tests to monitor your dosage
• Low molecular weight heparin (LMWH): This medication has longer-lasting effects and acts more predictably than UFH, meaning no regular blood monitoring is required

Warfarin

Warfarin is a longer-term anticoagulant therapy which works by blocking the action of vitamin K - a key molecule necessary in the clotting process. This treatment requires regular monitoring and blood tests to determine the correct dose and maintain a stable level. This is important as too high doses can lead to severe, uncontrolled bleeding. 

Direct oral anticoagulants

Direct oral anticoagulants (DOACs) work by directly inhibiting your blood’s ability to form blood clots. Different DOACs work via slightly different mechanisms to inhibit different elements of the clotting process. These medications are fast-acting and can be taken regularly without the need for regular laboratory monitoring.

When should anticoagulant therapy be used in pregnancy?

It is important to identify if and when anticoagulant therapy should be used in pregnancy to improve outcomes for both the mother and the baby. Anticoagulant therapy might be used in pregnancy for the treatment of VTE, as well as for the prevention of pregnancy-related complications in individuals who are at a higher risk of blood clots.⁵

You might be given full dose anticoagulant therapy if you:

• Develop a blood clot during pregnancy or postpartum (after birth)
• Have a previous history of multiple VTE events
• Have a prosthetic (artificial) heart valve
• Are already on long-term anticoagulants

Alternatively, you might be prescribed prophylactic (or preventative) anticoagulants if you are at higher risk of developing a blood clot. This might include:

• Family history of blood clots
• History of blood clots
• Thrombophilia - certain conditions which increase your risk of blood clots (e.g. factor V Leiden, antithrombin deficiency, antiphospholipid syndrome)
• Recurrent previous miscarriage or pregnancy loss
• Pre-eclampsia
• Prolonged bed rest (>4 days) or long-distance travel (e.g. air travel)

Even though all women are at higher risk of blood clots during pregnancy, this risk is still relatively low and routine anticoagulant therapy is generally not advised unless you are at higher risk. Your healthcare provider should be able to advise you on whether you need anticoagulation therapy during your pregnancy. 

What are the different anticoagulation therapies?

The choice of anticoagulant medications used during pregnancy is a careful balancing act to protect both the mother and the foetus. Several different options exist, each with its considerations:⁶

Unfractionated heparin (UFH)

UFH has a well-established safety profile during pregnancy and is often favoured for use during pregnancy as these drugs cannot cross the placenta and affect the foetus. UFH is particularly used in situations where rapid reversibility is required due to its short lifespan (e.g. around the time of delivery).

Low molecular weight heparin (LMWH)

LMWH does not cross the placenta and has a well-established safety profile for use in pregnancy. The medication is given by injection under the skin, usually at the top of your legs or atm. A doctor or nurse can do this, or you or a relative can be taught how to administer it at home.

Dalteparin is typically given, but if you have an adverse reaction, other LMWHs are available (e.g. tinzaparin, enoxaparin).

Warfarin

Warfarin is usually avoided in pregnancy because there are risks of serious complications for the baby. This drug can cross the placenta and cause foetal bleeding and teratogenicity, especially during your first trimester.⁷

If you are already taking warfarin, your healthcare provider should give you advice and counselling about the risks before you become pregnant. If you are currently pregnant, warfarin should immediately be substituted for a heparin-based therapy (e.g. LMWH). 

Warfarin therapy is safe for use postpartum and when breastfeeding.

Direct oral anticoagulants (DOACs) 

DOACs (e.g. dabigatran, apixaban, rivaroxaban) have not been extensively studied for their safety in pregnancy. It is thought that these drugs can cross the placenta, but it is not currently known how they affect the foetus. Therefore, DOACs are generally avoided during pregnancy as their safety is not fully understood.⁸

Aspirin

Aspirin is an antiplatelet agent rather than an anticoagulant, but it is often used in combination with anticoagulant agents (e.g. LMWH) to reduce the risk of blood clotting. It is particularly used to manage recurrent pregnancy loss associated with antiphospholipid antibodies. Low-dose aspirin is usually given throughout pregnancy as a daily tablet.⁹

Monitoring and dosing adjustments of anticoagulants in pregnancy

Regular monitoring of your blood coagulation factors by blood tests is important to make necessary dosing adjustments and ensure the anticoagulation therapy is working at the right level for you. Regular adjustments to your anticoagulant dosage may be necessary throughout your pregnancy to maintain effective therapeutic levels while minimising the risk of any side effects and complications.¹⁰

Adjustments to your anticoagulation therapy are especially critical around the time of labour and delivery as this is a period of high risk of bleeding for the mothers. As anticoagulants increase the risk of bleeding, temporary adjustments are made to minimise this risk during this period. This might include:

• Switching to UFH medication during the last few weeks of pregnancy because it has a shorter half-life than LMWH, meaning it is cleared quicker from your body
• Temporary discontinuation of your anticoagulant for a few hours before your anticipated delivery
• Close monitoring of your blood levels to avoid excessive anticoagulation

These adjustments might vary between individuals and will be decided in consultation with your healthcare team. 

What are the risks and complications of anticoagulant therapy during pregnancy?

Foetal Risks

Warfarin can cross the placenta and cause potential adverse side effects to the foetus, including:⁷

• Teratogenicity (foetal anomalies, e.g. nasal hypoplasia, skeletal abnormalities)
• Foetal bleeding and haemorrhage
• Foetal loss and miscarriage or stillbirth

With DOAC therapies, the potential foetal risks are currently unknown, although their use is associated with some evidence of foetal anomalies and a high risk of miscarriage.⁸ 

It is important to understand that, while these other anticoagulants might cause foetal complications, heparin-based anticoagulation therapies are considered safe to use in pregnancy. These medications cannot cross the placenta and are thought to pose little risk to the foetus.⁶

Maternal Risks

There are some maternal risks and complications which are typically associated with the use of anticoagulants in general, not just pregnancy-associated risks. These include:^11,12

General anticoagulant risks

• Increased risk of severe bleeding is the most common side effect of any anticoagulation medication

Heparin-specific risks

• Heparin-induced thrombocytopenia (HIT) predisposes someone to blood clotting. Type 1 HIT is relatively common (affecting around 10% of people taking heparin) and is not considered dangerous - it usually goes away after a week of stopping treatment. In contrast, type 2 HIT is rare and can be dangerous, causing widespread clotting in your body¹³
• Osteoporosis: Long-term use of heparin (>1 month) can cause bone weakening and fracture

Warfarin-specific risks

• Skin necrosis can result from warfarin use in rare cases, especially in areas with high adipose tissue (e.g. thighs, breasts)
• Osteoporosis: Long-term warfarin use has been associated with an increased risk of osteoporosis and bone fractures

DOAC-specific risks

• Gastrointestinal issues including indigestion or bleeding

Summary

In summary, anticoagulation therapy is important in pregnancy for the treatment of blood clots or for the prevention of potential blood clots in high-risk mothers. Managing anticoagulation therapy involves a delicate balance between preventing clot formation and minimising risks to both the mother and baby. This might involve the use of certain anticoagulant medications known to be safe in pregnancies, regular monitoring of your blood levels of coagulation factors, and temporarily adjusting your therapy before delivery and labour. Striking the right balance is essential for ensuring a safe and successful pregnancy while effectively addressing thrombotic risks.