Anticoagulant Therapy After Surgery

Introduction

You may have noticed that many patients receive medications post-surgery. Amongst the common prescriptions of antibiotics and painkillers, anticoagulation medications are also a notorious addition to the list. This is especially true for those undergoing major surgeries, requiring hospital stays or individuals with certain pre-existing medical conditions. In this article, we will delve into the role of post-surgical anticoagulation.

Understanding clot formation

When an individual acquires damage to their vessels, blood can easily leave that compartment. As such, it may pool into tissues and organs (internal bleeding) or leave the body (external bleeding). However, our blood contains vital components that protect us from constant bleeding. These include platelets, which are cells that clog up wounds or tissue injury, and clotting factors, which are involved in a cascade of reactions that allow for “clotting” of the blood and support the function of platelets.¹ If either component is increased beyond a normal range, the blood will be more viscous due to increased clotting. This concept of inappropriate clotting is known as thrombosis.

Impact of surgery on clot formation

Surgical procedures are stressors on the body and thus alter normal physiology. Virchow’s triad provides a simple way of categorising the risk factors for thrombosis.² This triad consists of vessel wall injury, hypercoagulability of blood, and stasis of blood. This nicely demonstrates surgery as a major trigger for thrombosis, as it correlates with all three components:

• Vessel wall injury: Invasive procedures and surgeries will involve damage, pressure or trauma to the blood vessels involved at the site of operation
• Hypercoagulability of blood: For individuals with pre-existing conditions such as cancer, inflammatory diseases, and blood disorders (e.g., thrombophilia), there is an increased risk of thrombosis. Additionally, pregnant individuals are more likely to be in a hypercoagulable state
• Stasis of blood: Major surgeries may involve patients being immobile for a while, so blood flow is not optimal

Blood clots can block vessels and reduce the blood supply to/from an area of the body. As a result, patients with thrombotic events can experience pain, swelling and redness (or pallor, depending on the obstructed vessel) of the affected site.³ This will also affect the rate of healing post-surgery and may lead to further complications such as infection or tissue death.

Certain body systems can be affected by inappropriate clot formation, and this can lead to severe outcomes. For example, thrombus formation in the coronary vessels (vessels that supply the heart) can lead to a myocardial infarction, essentially a heart attack. Thromboembolisms in the lung can lead to pulmonary embolism, presenting with acute shortness of breath and cardiorespiratory failure if not treated promptly. 

What are anticoagulation medications?

As mentioned earlier, the main two components of coagulation are platelets and clotting factors. Thus, anticoagulation medications can target either component. 

Blood thinners include Warfarin and Heparin; antiplatelets such as Clopidogrel; and direct oral anticoagulants (DOAC) such as Apixaban4. They may be given orally (as tablets or capsules) or via injections and will usually be given once a day. However, the frequency, duration and dose will depend on the individual case. Below are some of the common anticoagulation medications used postoperatively.

Warfarin

Warfarin served as a first-line anticoagulant for many years. Traditionally, this was prescribed for the management of atrial fibrillation (AF) and deep vein thrombosis (DVT).⁵ Its mechanism of action relies on the inhibition of an enzyme called epoxide reductase, which in turn prevents vitamin K from being reduced to its active form. The synthesis of certain clotting factors requires the presence of this active form of vitamin K, namely factors II, VII, IX, X and protein C.

Despite the success of warfarin, it has been superseded by DOACs in recent guidelines.⁶ For example, the National Institute for Health and Care Excellence (NICE), updated their guidance so that DOACs are now recommended first-line for anticoagulation in AF.⁷ To understand the reason behind this, it is important to address the drawbacks of warfarin administration. 

Firstly, regular monitoring is required for warfarin, as it can prolong the bleeding time. International Normalised Ratio (INR) provides a measure of bleeding time with regard to certain clotting factors, and patients on warfarin often have a target INR of 2.5. Thus, good maintenance and monitoring of INR for the duration of Warfarin use is essential. 

The use of warfarin can also be associated with other side effects, such as purple toes, teratogenicity, and skin necrosis.⁸

Heparin

Heparin is used in two forms: unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Heparin acts by enhancing the potency of the molecule antithrombin, which in turn reduces coagulation.⁹ 

Much like warfarin, heparin has been used for many years and still remains a commonly used anticoagulant. For example, patients with a long hospital stay or at increased risk of venous thromboembolism (VTE), may receive daily enoxaparin (LMWH).¹⁰ 

One complication of heparin, particularly UFH, is heparin-induced thrombocytopenia (HIT), which features a reduction in platelets greater than 50%, due to an immune-mediated reaction. However, with the development of LMWH, this risk has been significantly reduced.⁹ Nonetheless, UFH remains a more appropriate option for patients with renal failure.

Antiplatelets

Aspirin is the most commonly prescribed antiplatelet drug for cardiovascular diseases.⁹ It acts by irreversibly inhibiting the cyclooxygenase 1 and 2 (COX) enzymes, resulting in reduced prostaglandin H2 (PGH2), which is associated with various roles such as platelet aggregation. 

Recent guidelines have been adjusted to recommend other antiplatelet medications such as Clopidogrel (targeting the P2Y12 receptors in platelets), for the first-line treatment of ischaemic strokes and peripheral arterial disease.¹¹ However, aspirin is still widely used for prophylactic anticoagulation post-orthopaedic surgeries. For example, elective hip surgeries may involve a VTE prophylaxis course of 10 days of LMWH, followed by aspirin for a further 28 days.

Direct oral anticoagulants/ novel oral anticoagulants (DOAC)

DOAC refers to a group of anticoagulants with a similar mechanism of action, mainly leading to the inactivation of factor X. This group includes Rivaroxaban, Apixaban, Edoxaban and Betrixaban. They have become increasingly preferable due to their rapid action as well as their short half-life. Hence, planning for interruption and re-initiation of the medications with regard to surgery is easier.⁹ 

DOACs have replaced Warfarin as a first-line treatment in several guidelines, as constant monitoring of INR is not required for DOACs. On the other hand, care should be taken when administering direct oral anticoagulants for patients with renal impairment, as DOACs can worsen this.

Who receives anticoagulation?

Clinicians will risk-assess patients based on their demographic, medical background, and the type of surgery they are undergoing. Major surgeries include those done under general anaesthesia. For example, most orthopaedic surgeries and open abdominal surgeries would require patients to receive some anticoagulation therapy after surgery.¹² Additionally, a number of medical conditions would require postoperative anticoagulation; these include:

• Heart conditions: atrial fibrillation, angina, myocardial infarction
• Stroke
• Past episodes of deep vein thrombosis or pulmonary embolisms

Each case will be assessed to identify high-risk individuals. Some individuals are prone to increased bleeding, so clinicians will aim to balance the risk of bleeding against the risk of clotting. 

It is also important to note that anticoagulant therapy can be given prophylactically or therapeutically. This means that, as per perioperative guidelines, many individuals receive prophylactic anticoagulants to reduce the risk of thrombosis-related complications and improve post-operative outcomes.

What are the adverse effects of anticoagulation medications?

The main side effects to consider are increased risk of bleeding and allergies (detailed below). Other side effects vary depending on the prescribed medication but may include nausea, diarrhoea/constipation, headaches, and indigestion.⁸

Increased risk of bleeding

As anticoagulant therapy aims to reduce clotting, inappropriate administration can lead to increased bleeding. Regular monitoring and medication reviews should address this potential side effect. Special considerations should be given to patients with pre-existing bleeding disorders or high bleeding risks, such as haemophilia and thrombocytopenia. Bleeding can present in many ways, including increased bruising, bleeding gums, heavy menstruation and passing blood in urine or stool.

Allergy

This is a potential adverse effect of any medication. Hypersensitivity can range from developing itchy skin/rashes to more severe reactions such as fainting, swellings, difficulty breathing and palpitations. The latter symptoms indicate an anaphylactic reaction, and this prompts urgent medical attention.

Summary

Anticoagulation therapy is essential for a wide range of surgical cases, and adhering to the prescribed medications can enhance the healing process and reduce post-surgical complications. If there are any issues or concerns with the medications, seek urgent medical attention, as relevant adjustments can be made.