Risk of Bleeding from Anticoagulant and Antiplatelet Medications: Clinical Implications

Coagulation disorders acquired through antithrombotic therapy: implications for dentists

Summary

Antithrombotic medications are one of the most common causes of an acquired bleeding disorder. Most of these medications are administered orally for a variety of clinical indications.

It is important for dental surgeons to know these medications, their mechanisms of action, and how they can influence patients’ dental management, particularly when performing procedures that carry a risk of bleeding.

Bleeding disorders are characterized as acquired or inherited. Bleeding disorders can be acquired through diseases, medications, or a combination of both.1 Liver disease, thrombocytopenia resulting from autoimmune destruction through immune thrombocytopenic purpura (ITP), or bone marrow disorders and kidney failure serious are the most common causes of the appearance of diseases. of an acquired bleeding disorder.

This article will focus on bleeding disorders acquired by antithrombotic therapy.

Antithrombotic drugs can be divided into three categories:

1. Antiplatelet medications : They work by disrupting platelet aggregation

2. Anticoagulant medications : These medications affect thrombus formation by acting on the coagulation cascade.

3. Fibrinolytic drugs : This group of drugs has a thrombolytic effect by binding to clots and converting plasminogen to plasmin. Plasmin, in turn, breaks down the fibrin matrix of the clot. Drugs in this group are indicated mainly after a myocardial infarction and are administered intravenously. Therefore, they will not be discussed further.

A triad for thrombus formation, first described by Virchow, provides an overview of the risk factors that may be associated with such an event. These are:

• Damage to the vessel wall

• Hypercoagulability

• Stasis

Main indications for antiplatelet therapy

• Primary prevention of atherothrombotic events in those who are at high risk.

• Secondary prevention of atherothrombotic events in people with acute coronary syndrome, angina, peripheral arterial disease and atrial fibrillation.

• Secondary prevention of cardiovascular events after myocardial infarction (MI), stent implantation, transient ischemic attack or stroke.

• The prevention of atherothrombotic events in those undergoing percutaneous coronary intervention.

• Primary prevention of cardiovascular diseases in people at high risk of myocardial infarction or stroke.

Antiplatelet medications

Antiplatelet medications available in the UK can be classified into four groups:

1. aspirin

2. Thienopyridines – clopidogrel, ticagrelor and prasugrel

3. dipyridamole

4. Glycoprotein IIB/III inhibitors: abciximab, eptifibatide and Tirofiban.

Dental implications of antiplatelet therapy

Patients may have varying degrees of sensitivity to the actions of antiplatelet medications. There is no adequate test, such as the INR used for patients treated with warfarin, to assess the risk of bleeding in those receiving antiplatelet therapy.

Aspirin monotherapy has been shown to increase bleeding time in patients. Patients receiving dual antiplatelet therapies may demonstrate prolonged bleeding times compared to monotherapy.

Clopidogrel is a more potent agent compared to aspirin.

The newer antiplatelet agents, ticagrelor and prasugrel , are considered to have stronger effects than clopidogrel and are only prescribed in combination with aspirin. Therefore, all of this must be taken into account with respect to bleeding risk assessment. It is important to note that there is limited evidence on the risk of bleeding associated with ticagrelor and prasugrel in relation to dental procedures.

When treating patients with antithrombotic medications, clinicians must weigh the risk of perioperative and postoperative bleeding due to continued drug treatment against the risk of thromboembolic events due to discontinuation or discontinuation of the drug.

There is strong evidence showing an increased risk of thromboembolic events after discontinuation of antiplatelet therapy. Some studies include patients who stopped antiplatelet therapy before dental surgery. These events that affect those patients who have had a stent placed. These patients will be prescribed dual antiplatelet therapy for a period of up to 12 months.

Based on this evidence, available guidance recommends not suspending or discontinuing antiplatelet medication before invasive dental procedures, whether in monotherapy or dual therapy. This is because the risk of thromboembolic events is higher and more catastrophic, compared to prolonged bleeding time as a result of surgery, which can be managed effectively with local hemostatic measures.

Prescribing practice should be adjusted for patients taking antiplatelet medications. NSAID medications should be avoided for analgesic use due to the risk of increased bleeding when taken concurrently with antiplatelet therapies. Additionally, NSAIDs taken simultaneously with aspirin may interfere with the cardioprotective effects of low-dose aspirin.

As clopidogrel is metabolized in part by the enzyme CYP2C19, a member of the cytochrome P450 superfamily, any medication that inhibits this enzyme will result in a reduction of available active metabolite. Fluconazole inhibits CYP2C19 and should therefore be avoided.

Dental implications of anticoagulant therapy

There is evidence suggesting an increased risk of thromboembolic events due to discontinuation of warfarin therapy. A systematic review suggested that the risk increases by 0.2% when oral anticoagulant treatment is stopped before a surgical procedure.

The literature suggests that the probability of clinically significant postoperative bleeding after a dental procedure, as defined by Lockhart et al., is low for those patients who continue warfarin therapy without interruption.

Evidence also points to the majority of postoperative bleeding being managed effectively by local hemostatic measures , including pressure, tamponade with hemostatic material, and suturing, when the INR is within a safe range.

It is clear from a comprehensive literature search that, after considering the risk of thromboembolic events versus the risk of bleeding as a result of invasive dental procedures, most patients can undergo such dental treatment without discontinuing their warfarin therapy.

Guidance produced by the Scottish Dental Clinical Effectiveness Program (SDCEP) recommends that the INR level should be <4.0 so that dental procedures likely to cause bleeding are performed safely in primary care practice. It is recommended that the patient’s INR levels should be checked 24 hours before treatment, or up to 72 hours when INR levels are stable.

A stable INR is defined as one that does not require weekly monitoring or where no INR measurements > 4.0 have been recorded in the last two months. Therefore, it is important for all warfarinized patients to bring their anticoagulant therapy booklet, mentioned above, to the dental office for evaluation by the doctor.

Unlike warfarin, INR measurement is not recommended to evaluate the anticoagulant activity of direct oral anticoagulants (DOACs), nor is routine monitoring of these drugs required due to their predictable effects on coagulation levels.

It is clear that there is limited evidence available evaluating the risks of bleeding due to dental procedures in relation to patients taking DOACs.

A review of the literature concluded that patients taking DOACs with normal renal function can be safely and effectively managed with local hemostatic measures after simple extraction procedures. In those patients in whom the procedures may result in an increased risk of bleeding, discontinuation of medication may be considered. This can be accomplished by delaying or skipping a dose.

As mentioned above, the half-life of direct oral anticoagulants (DOACs) is considerably lower than that of warfarin. Therefore, in those patients who have normal renal function, the pharmacokinetic properties of these drugs allow modification of the drug regimen to rapidly alter coagulation levels. This would provide a window of time to perform procedures that carry an increased risk of bleeding, before anticoagulant therapy is recommended and therapeutic coagulation levels are restored.

The SDCEP guideline recommends not adjusting direct oral anticoagulant (DOAC) therapy for those dental procedures that carry a low risk of bleeding complications. However, it recommends alteration of DOAC therapy before those procedures that carry a higher risk of bleeding complications, such as more than three simple extractions in one session. The guidance recognizes that these are conditional recommendations due to the lack of available evidence.

In those patients taking dabigatran or apixaban , this would mean skipping the morning dose and restarting therapy as long as hemostasis has been achieved and maintained for four hours. In those patients taking rivaroxaban or edoxaban, this would mean delaying their dose until four hours post-hemostasis.

It is important to specifically mention that there is no evidence to suggest that the placement of local anesthetics , including the inferior alveolar nerve block technique, causes significant bleeding in patients on anticoagulant treatment.

Prescribing medications for this group of patients should also be considered . Paracetamol alone, or in combination with codeine, is the recommended analgesic for those taking oral anticoagulants, due to the possible interaction with NSAIDs. The choice of antimicrobial will also be influenced by oral anticoagulant therapy. Warfarin interactions have been detailed previously.

However, the interaction of warfarin with the topical antifungal miconazole should be highlighted because its potential severity is overlooked. Miconazole oral gel may be prescribed for the treatment of oral candidiasis. If prescribed together with warfarin, it may enhance anticoagulant activity and should therefore be avoided. For these patients, nystatin is a suitable alternative therapeutic option.

With respect to direct oral anticoagulants (DOACs), it would be prudent to avoid the macrolide antibiotic group if possible, due to the risk of increased anticoagulant activity with concomitant treatment. Commonly prescribed antimicrobials, such as penicillin-based antibiotics and metronidazole, are safe to use in this group.

Carbamazepine , which may be prescribed for the treatment of trigeminal neuralgia , may decrease DOAC activity and should therefore be avoided.51