Antithrombotics

1. Patients at Risk of Prolonged Bleeding

   
   

   

What are anti-thrombotic drugs used for?

Antithrombotic drugs are indicated to prevent or treat blood clots, which can block blood vessels and lead to serious conditions like heart attacks, strokes, or deep vein thrombosis (DVT). Blood clots can form in the arteries or veins due to various factors, including certain medical conditions, genetic factors, prolonged immobility, or surgical procedures. Antithrombotic drugs work to reduce the formation or growth of these clots, thereby lowering the risk of these potentially life-threatening events. They increase the risk of prolonged healing for patients undergoing invasive dental surgeries. These drugs are generally divided into three main types:

1. Antiplatelet drugs – prevent platelets from clumping together to form a clot. Commonly used in people with heart disease or after a heart attack.

These include P2Y12 inhibitors such as clopidegrel and prasugrel and tricagrelor, aspirin and dipyridimide. Dual antiplatelet therapy is usually prescribed for a certain duration.

2. Anticoagulants – reduce the blood's ability to clot. Used in conditions like atrial fibrillation or after certain surgeries.

Warfarin is an oral anticoagulant that inhibits the production of Vitamin K dependent factors. Warfarin blocks the enzyme vitamin K epoxide reductase (VKOR), which is necessary for recycling vitamin K back into its active form after it has been used to activate clotting factors. Vitamin K is essential for the synthesis of clotting factors II (prothrombin), VII, IX, and X, as well as proteins C and S, which are natural anticoagulants.The international normalised ratio (INR) indicates the extent of anti-coagulation in patients taking warfarin.

Non-vitamin K dependent antagonist oral anti-coagulants include direct thrombin inhibitors such as dabigatran and factor Xa inhibitors (e.g. apixaban, rivaroxaban). Unlike the INR in warfarin therapy, there is no test to indicate the extent of anticoagulation in patients taking NOACs.

3. Thrombolytics – dissolve clots after they've formed. Usually reserved for emergency situations like an ongoing stroke or heart attack.

By reducing clot risk, these drugs help maintain smooth blood flow and prevent blockages that can cause severe complications.

Thrombolytics include heparin and low molecular weight heparins (enoxaparin). They are usually prescribed for a short duration.

Which other medical conditions or patient -related factors increase the risk of prolonged bleeding?

The risk of bleeding during dental or oral procedures is increased by factors that interfere with normal blood clotting (hemostasis), particularly those affecting platelet function or the coagulation cascade. Common causes include elevated blood pressure, which can increase bleeding tendency, and liver and kidney disease, which impacts the production of clotting factors essential for blood coagulation. Congenital bleeding disorders, like Hemophilia A/B or von Willebrand disease, also compromise the body’s ability to control bleeding effectively. Chemotherapy may contribute to bleeding risk through secondary thrombocytopenia (a reduction in platelet count). Older age or frailty, poor anti-cogulant control, history of bleeding, prior stroke and hazardous alcohol consumption are some other risks.

What do we need to inform the patient at risk of bleeding before undergoing an oral or dental procedure?

1. Increased Bleeding:

   • Even minor dental procedures, like tooth extractions or subgingival gum cleanings, can lead to prolonged bleeding.

   • Soft tissues in the mouth are sensitive, and blood flow in these areas can be harder to control when bleeding begins.

2. Difficulty in Stopping Bleeding:

   • The antithrombotic effect may make it more challenging for the body to form clots. As a result, bleeding may take longer to stop, requiring additional interventions like local hemostatic agents or sutures.

3. Complications with Certain Procedures:

   • More invasive procedures, like surgical extractions, implant placements, or bone grafts, pose a higher bleeding risk and may require specialized planning.

4. Bruising and Hematoma Formation:

   • Due to the reduced clotting ability, patients on antithrombotics may bruise more easily. If bleeding occurs internally in the mouth or jaw, it may lead to hematomas, which can be painful and require further medical management.

   

What is the risk of prolonged bleeding with different oral and dental procedures?

Risk of prolonged bleeding	Procedure
Unlikely	examination and diagnostic procedures (periodontal examination, impressions), restorative treatments (restorations, root canal therapy), orthodontic treatment
Lower	extraction of a small number of teeth that are no adjacent, periodontal procedures (e.g. subgingival debridement), incision and drainage of swellings, limited or small soft tissue biopsies
Higher	extraction of a large numbeer of teeth (4+) or extraction of adjacent teeth that creates a large wound, procedures where a mucoperiosteal flap is used (surgical extractions, implant placement, periapical surgery, periodontal surgery), extensive soft tissue biopsies, hard tissue biopsies

2. Management of Prolonged Bleeding Risks

What are some local haemostatic measures to stop bleeding?

To manage these risks, dental professionals may work closely with a patient's physician to tailor care. Sometimes, local measures can control bleeding without needing to adjust the antithrombotic therapy.

In managing bleeding risks for patients on antithrombotics during dental procedures, various techniques and agents can be used to help control bleeding.

1. Pressure

- Applying firm pressure with gauze directly over the bleeding site can help control bleeding and allow clot formation. It’s often the first-line approach for minor bleeding.

2. Clot Stabilizing Agents (e.g., Surgicel, Gelfoam, Collagen, Cellulose)

- These agents provide a scaffold that promotes platelet adherence and clot formation.

- Use: Place the stabilizing agent in the socket or wound, then optionally suture over it for added stability. Apply pressure with gauze afterward to enhance clotting.

3. Sutures to close wound

- Suturing the wound can help hold tissue together and minimize bleeding. This is often used for extractions or surgical procedures in the mouth to stabilize the area.

4. Adrenaline in Local Anesthetic (LA)

- Adrenaline (epinephrine) is often included in local anesthetics to constrict blood vessels, which reduces blood flow to the area and helps control bleeding during the procedure.

5. Bone Wax

- Bone wax is used to block bleeding from exposed bone vessels, particularly when the bleeding originates within the bone itself.

- Use: Place a small amount of wax directly on the bone and press it into the pores to stop the bleed. Remove any excess wax as it does not resorb and can cause a foreign body reaction if left in place.

- Caution: This method is typically a last resort due to the non-resorbable nature of bone wax.

6. Electrocautery

- This technique uses heat to cauterize and seal blood vessels. It’s effective for larger or deeper bleeds and can help in achieving hemostasis where other methods are insufficient.

7. Tranexamic Acid 4.8% for patients taking warfarin

- Tranexamic acid works by preventing the breakdown of fibrin, which helps stabilize clots. It’s commonly used for patients on anticoagulants.

- Use:

• Mouthwash is typically applied before surgery. Following procedure, it can be used to soak gauze, then placed over the wound to aid in clot stability and reduce bleeding. Patients can also use it after the procedure, 10mL rinsed for 2 minutes and then spat out, 4 times for 2 days.

These methods are generally selected based on the extent of bleeding, the invasiveness of the procedure, and the patient's anticoagulation status.

What happens if the bleeding does not stop, bleeding restarts?

If there is persistent oozing or bleeding, bleeding that restarts, or any bleeding of concern, seek urgent medical attention. Advise the patient they may have extensive bruising.

Can you still take pain medication?

Paracetamol is the preferred analgesic for post - operative pain in patients taking antithrombotic drugs - concomitant use of non-steroidal anti-inflammatory drugs and antithrombotic drugs increases the risk of postoperative bleeding. Typical dosage:

Paracetamol 1000mg orally, 4 - 6 hourly (to a maximum of 4g in 24 hours) for the shortest duration possible

However, note that this cannot be prescribed by patients with severe kidney impairment, severe heart failure, active gastrointestinal ulcer or gastrointestinal bleeding, patients with bleeding disorders, patients taking corticosteroids or anticoagulants, or patients with multiple risk factors for increased NSAID toxicity (e.g. elderly patients with a history of gastrointestinal bleeding).

NSAIDS increase the risk of bleeding in patients taking antithrombotic drugs.

Review the patient for two days after the procedure to check for pain, bleeding, delayed healing or infection, and treat as necessary.

Are there any medication specific management protocols?

In dental practice, the consequences of a thromboembolic event are usually more significant than the consequences of bleeding.

Patient	Management
Triple antithrombotic therapy	Consult clinician in charge of antithrombotic therapy before performing any oral and dental procedure AND consider specialist referral
An oral anticoagulant PLUS an antiplatelet drug	If possible, delay oral and dental procedures until patient finishes the antithrombotic therapy (aspirin, clopidegrel, prasugrel, ticagrelor, dipyridamole) as prescribed for a specific duration. In regards to anti-coagulant drugs, seek medical practioner's opinion on wherther if temporary interruption is needed. Otherwise, ask specialist referral. If temporary interruption is not required, for patients taking warfarin check INR within 24 hours before the procedure. If INR is 3.5 or less, perform the procedure. Otherwise, refer the patient for medical assessment and stabilisation of INR.
Single oral anticoagulant OR dual antiplatelet therapy	Temporary interruption is not required unless it is a lower risk procedure with patient related bleeding factors, or procedures with a higher risk of bleeding. Follow INR protocols if there is no temporary interruption and patient is taking warfarin.
Single anti-platelet drug	Only seek for temporary interruption if it is procedure that involves higher risk of prolonged bleeding.
injectable anti-coagulant underdoing an oral or dental procedure	delay elective procedures until after the anti-cogulant therapy has stopped. Refer patients to hospital for emergency or semi-elective procedures.

Are there specific protocols for managing patients on warfarin?

For patients taking warfarin, it is essential to assess bleeding risk prior to any dental or surgical procedure. The primary method for this is measuring the patient’s International Normalized Ratio (INR), which is calculated as the ratio of the patient’s prothrombin time (PT) to a standardized PT value. For safe treatment, it is recommended to recheck the INR within 24 hours before the procedure. If the INR is below 3.5, the procedure can proceed with local hemostatic measures in place to manage potential bleeding. However, if the INR is 3.5 or above, the procedure should not be performed, and the patient should be referred to their physician to adjust warfarin levels.

Since warfarin is metabolized in the liver through the cytochrome P450 enzyme system, certain medications, such as azole antifungals, are contraindicated because they compete for the same enzyme and may cause warfarin to accumulate in the bloodstream, increasing bleeding risk.

In cases of excessive bleeding in warfarin patients, there are several treatment options. Vitamin K supplementation can help to promote clotting, while a blood transfusion (either whole blood or plasma) may be necessary to replace clotting factors. For severe cases, administering a Factor IX complex can also help to control bleeding effectively.