Influence of Anticoagulants on Dental Surgical Procedures

INTRODUCTION

As the age has advanced, there has been a high incidence of cardiovascular diseases in developed societies. Millions of subjects adhere to some or the other protocol of anticoagulant therapy. The main objective of the therapy is to reduce the occurrence of thromboembolism, i.e. in those subjects who have a history of angina, atherosclerosis, cerebro-vascular accidents, atrial fibrillation, ischaemic heart disease, deep vein thrombosis, peripheral artery disease, myocardial infarction and pulmonary embolism, and also in patients after angioplasty and stent placement, bypass surgery and prosthetic heart valve placement.¹ Platelet activation and aggregation is considered to be central to arterial thrombus production due to which antiplatelet agents and anticoagulants have been extensively researched and developed as potential therapies for the prevention and management of arterial thrombosis.² Antiplatelet and anticoagulant therapies have always been associated with increase in perioperative and postoperative haemorrhage. This article reviews most commonly used antiplatelet and anticoagulants drugs in the society and explains the management of these patients when they are submitted to various oral surgical procedures.

HAEMOSTASIS

Haemostasis involves interactions between four biologic systems: blood vessel wall, blood platelets, blood coagulation system, and the fibrinolytic system. Constriction of blood vessel is the essential first stage. Platelet adhesion and aggregation follows vessel constriction after which blood clotting mechanism is initiated by either intrinsic or extrinsic pathway. There is a cascaded reaction sequence in which there is activation of inactive factors which catalyze the formation of products from precursors and also activate more factors until final products are formed.

Previously bleeding time, prothrombin time and partial thromboplastin time had been used as the standards by which clinicians evaluate anticoagulation levels. An International Normalized ratio (INR) have been introduced by the World Health Organization Committee on Biological Standards in the year 1983 to assess patients receiving anticoagulation therapy more accurately.⁴

The INR is calculated from the ratio of paient’s Prothrombin time (PT) and control PT, raised to the power international sensitivity index (ISI). It is more reliable in determining anticoagulation level since it depends upon patient’s blood and on sensitivity of thromboplastin reagent and assigned ISI value. A patient with normal coagulation status would have an INR of 1.0.4 The INR should be checked on the day of operation or, if that is not possible, the day before. For patients with constant INR levels of up to 2.5 needing emergency surgery, the doctor should rely on the last known INR level, provided it was determined within 1 week before surgery.³

ORAL ANTICOAGULANT AGENTS

Two most commonly prescribed oral anticoagulant agents are: first being the Anticoagulant group including Warfarin Sodium & Heparin and second group is antiplatelet agents including Acetylsalicylic acid & Clopidogrel.⁵

Warfarin is an antagonist of Vitamin K. Clotting factors namely Factor II, VII, IX and X and Proteins C and S, are biologically inactive without the carboxylation of certain glutamic acid residues. This carboxylation process requires a reduced vitamin K as a cofactor. Antagonism of vitamin K or a deficiency of this vitamin reduces the rate at which these factors and proteins are produced, thereby creating a state of anticoagulation.²

Heparin has a very short life and thus it is usually administered by a continuous intravenous infusion for short-term inpatient use. Its acts indirectly by activating plasma Antithrombin III. The heparin Antithrombin III complex then binds to clotting factors of the intrinsic and common pathways (Xa, IIa, IXa, Xia, XIIa and XIIIa) and inactivates them. Although newly developed low-molecular-weight heparin has improved pharmacokinetics and may be used on an outpatient basis.⁵

NSAID are also used in the treatment and prevention of thromboembolic diseases. The antithrombotic action of Acetylsalicylic Acid (ASA) depends on the irreversible inhibition of arachidonate cyclo-oxygenase activity in platelets, thereby reducing the extent of thromboxane A2 formation which is an effective inducer of platelet granule secretion as well as platelet aggregation. Available evidence suggests that a daily dose of 75-150 mg is recommended for long term prevention in high risk patients. In clinical situations where an immediate antithrombotic effect is required (such as acute MI, or stroke), a loading dose of 300 mg is recommended.²

Clopidogrel : The antiplatelet activity of clopidogrel is greater than that of ASA. It is mainly used in the patients who are on secondary prevention of CVA, myocardial infarction and peripheral arterial insufficiency. Due to its high cost it is used only selectively in patients who are resistant to treatment with ASA. The antiplatelet effect of clopidogrel is irreversible and lasts for the life of the platelet (7 to 10 days).²

ORAL SURGICAL PROCEDURES AND ANTICOAGULATION THERAPY

The goal of managing anticoagulated patients who need surgery is to prevent major or life-threatening bleeding while protecting against thromboembolism. Major surgical procedures such as intra-abdominal, intra-thoracic, major cancer surgery, removal of head and neck tumors, and extraoral open reduction of facial fractures are associated with considerable bleeding while procedures including single and multiple dental extractions, full mouth extractions, and alveolectomies are associated with very little amount of bleeding.⁶

Antiplatelet medications can double the normal bleeding time, but mostly these values are within or just outside the normal range. It has been reported that only 20% to 25% of patients using ASA have an abnormal bleeding time.² Patients taking antiplatelet medications may have a prolonged bleeding time, but this is very rarely clinically relevant since postoperative bleeding can be mostly controlled using local haemostatic measures in cases of minor dental procedures.

A study was done by Ardekian et al.⁷, investigating stopping versus continuing low- dose ASA prior to dental extraction. Thirty-nine patients who were taking ASA 100mg daily were studied. Nineteen subjects took ASA as prescribed, while 20 stopped taking ASA seven days before the planned date of extractions. A bleeding time test was conducted one hour prior to the procedure. The mean bleeding time in patients who continued ASA was longer as compared to those who stopped (3.1 min vs 1.8 min, P = 0.004). Although the difference was statistically significant, none of the patients had a bleeding time outside the normal range (2-10 min) who continued ASA. Intraoperative bleeding was controlled in 33, i.e. 85% of the patients with gauze packing and sutures alone. Six patients (2 who stopped ASA and 4 who continued ASA) had tranexamic acid added to the local packing. At the end of the study, it was observed that no patient experienced uncontrolled bleeding immediately after the procedure or in the following one week.

There are only few published studies on the relative risks of perioperative bleeding with clopidogrel. The pharmacological mechanisms underlying the antiplatelet action of clopidogrel suggest that patients who are taking these medications will be at equal risk to those who are taking ASA.⁸Based on the above mentioned studies, it is suggested that these medications should not be discontinued prior to dental surgical procedures.

Before discussing the influence of various anticoagulants on oral surgical procedures, lets discuss the various criteria which conforms postoperative bleeding. Lockhart et al.⁹ suggested that postoperative bleeding is considered to be significant if it conforms to the following four criteria:

• The bleeding continues beyond 12 hours;
• It causes the patient to call or return to the dental practice or accident and emergency department;
• Results in the development of a large haematoma or ecchymosis within the oral soft tissues and;
• Requires a blood transfusion.

Patients, in the past, who were at higher risk of experiencing thromboembolism and required surgery such as oral extractions were admitted to hospital four days prior to oral surgery. In this protocol, termed “heparin windows”, warfarin was discontinued and unfractioned heparin was administered in multiple doses with PT and INR being monitored after each dose. Warfarin was readministered immediately postoperatively, and unfractioned heparin administration was stopped. Patient remained in the hospital until adequate therapeutic levels of warfarin were achieved. This heparin window technique was costly and required ample amount of time. In such patients low molecular weight heparins (LMWHs) can be used. Because of higher bioavailability of LMWHs (95 percent), continuous PT and INR testing is unnecessary and patient can also self administer the drug. Patient may undergo outpatient surgery and reinitiate warfarin therapy under the guidance of their physicians.⁵

There have been many clinical studies published on the relative risks of perioperative or postoperative bleeding with warfarin. In 1998, Devani & colleagues performed a study on various clinical protocols for the management of warfarinised patients needing dental extractions. This study was designed to compare two approaches in the management of these patients. A control group of 32 patients had their warfarin treatment stopped for 2-3 days prior to having dental extractions, resulting in a reduction in the average preoperative international normalised ratio (INR) from 2.6 to 1.6. The study group of 33 patients did not have their anticoagulant treatment altered before extractions, and had an average preoperative INR of 2.7. All patients were treated under local analgesia on an outpatient basis, and local measures-consisting of Surgical pack and sutures-were used in all cases to control postoperative bleeding from extraction sockets. None of the patients had any immediate postoperative bleeding, and only 1 patient from each group had mild delayed haemorrhage, which was easily controlled with local measures. It is proposed that, provided the INR is within the therapeutic range of 2.0 to 4.0 and local measures are used to control postoperative bleeding, there is no justification in altering warfarin treatment prior to dental extractions in these patients, and thereby exposing them to the risk of thromboembolism.¹⁰

Wahl reviewed the literature on this subject in 2000 reporting that Of more than 950 patients receiving continuous anticoagulant therapy (including many whose anticoagulation levels were well above currently recommended therapeutic levels) who underwent more than 2,400 surgical procedures, only 12 (< 1.3 percent) required more than local measures to control hemorrhage. Only three of these patients (< 0.31 percent) had anticoagulation levels within or below currently recommended therapeutic levels. Of 526 patients who experienced 575 interruptions of continuous anticoagulant therapy, five (0.95 percent) suffered serious embolic complications; four of these patients died. Serious embolic complications, including death, were three times more likely to occur in patients whose anticoagulant therapy was interrupted than were bleeding complications in patients whose anticoagulant therapy was continued (and whose anticoagulation levels were within or below therapeutic levels). Interrupting therapeutic levels of continuous anticoagulation for dental surgery is not based on scientific fact, but seems to be based on its own mythology.¹

In 2000, Blinder & Manor performed a study. The purpose of this study was to evaluate the incidence of postoperative bleeding in patients treated with oral anticoagulant medication who underwent dental extractions without interruption of the treatment and to analyze the incidence of postoperative bleeding according to the International Normalized Ratio (INR) value. The 249 patients who underwent 543 dental extractions were divided into five groups: Group 1 with INRs of 1.5-1.99, Group 2 with INRs of 2-2.49, Group 3 with INRs of 2.5-2.99, Group 4 with INRs of 3-3.49 and Group 5 with INRs>3.5. The INR was measured on the day of the procedure. Local haemostasis was carried out with gelatin sponge and multiple silk sutures. The incidence of postoperative bleeding was not significantly different among the five groups. The value of the INR at the therapeutic dose did not significantly influence the incidence of postoperative bleeding. Thus, dental extractions can be performed without modification of oral anticoagulant treatment. Local haemostasis with gelatin sponge and sutures appears to be sufficient to prevent postoperative bleeding.¹²

In 2000, ardekian and colleagues evaluated 39 patients who were scheduled to undergo dental extractions. All patients were receiving 100 milligrams of aspirin daily on a regular basis. The authors randomly divided the patients into two groups: those who stopped the aspirin therapy before the procedure and those who continued the aspirin therapy. One hour before the procedures, all patients underwent a bleeding time test. The mean bleeding time was 1.8 +/- 0.47 minutes for patients who stopped aspirin therapy one week before the procedure and for patients who continued aspirin therapy, the bleeding time was 3.1 +/- 0.65 minutes. The difference was statistically significant (P = .004). However, both groups were within the normal bleeding time range, and in both groups, a local haemostatic method was sufficient to control bleeding. No episodes of uncontrolled intraoperative or postoperative bleeding were noted. It was concluded that low-dose aspirin therapy should not be stopped before oral surgery. Local hemostasis is sufficient to control bleeding.¹³

In 2003, Zanon and colleagues evaluated the incidence of bleeding complications after dental extraction in a group of 250 consecutive anticoagulated patients and 250 non-anticoagulated patients (control group). In all patients, anticoagulant treatment was not changed (International Normalized Ratio, 1.8-4) and local haemostatic measures (fibrin sponge, silk suture and a gauze saturated with tranexamic acid) were used. All procedures were performed in an outpatient clinic setting. There were four bleeding complications registered in the group of anticoagulated patients and three in the control group. The difference of bleeding complications in the two groups was not statistically different (relative risk, 1.14; 95% confidence interval, 0.29-6.04; P = 0.7). None of the post-operative late bleeding required hospitalization and/or blood transfusions, and further local measures were sufficient to stop the bleeding.¹⁴

Heparin is also used for acute thromboembolic episodes or for hospitalization protocols that include significant surgical procedures. Heparin is administered subcutaneously or intravenously to prevent deep venous thrombosis and pulmonary emboli. PT, APTT, and thrombin times are prolonged. Most patients are monitored with the APTT and are maintained at 1.5 to 2.5 times the control value. Large doses of heparin can increase the INR. Platelet counts also should be monitored if heparin is used for more than 5 days because heparin can cause a thrombocytopenia. Heparin is available as standard or unfractionated heparin or low–molecular weight (LMW) heparins. The anticoagulant effect is usually lost within less than 6 hours of stopping heparin. Low-dose heparin therapy may have little effect either on the APTT or on postoperative bleeding. LMW heparins are more completely absorbed from subcutaneous sites and have a longer duration. Heparin has an immediate effect on blood clotting but acts for only 4 to 6 hours, so no specific treatment is needed to reverse its effect. The effect of heparin is best assessed by the APTT. For uncomplicated forceps extraction of 1 to 3 teeth, there is usually no need to interfere with anticoagulant treatment involving heparin or LMW heparins or antiplatelet drugs. Medical consultation should be sought before more advanced surgery is required. When heparin therapy is stopped, any surgery can safely be carried out after 6 to 8 hours, when the effects of heparinization have ceased. In patients for renal dialysis, or patients with cardiopulmonary bypass or other extracoporeal circulation with heparinization, nonelective surgery is best carried out on the day after dialysis because the effects of heparinization have then ceased and there is maximum benefit from dialysis. LMW heparins appear to have little effect on postoperative bleeding, despite their longer activity (up to 24 hours).³

ROLE OF ANTICOAGULANTS ON IMPLANT THERAPY

Since the past decade there has been a revolution in dentistry with the evolution of implants. For the success of the implants placed a surgical planning is needed. Some patients are on oral anticoagulation therapy (OAT) and are undergoing implant therapy.

In 2009, Madrid and Sanz gave a systemic review to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy patient undergoing implant therapy and to provide a management protocol to patients under oral anticoagulation therapy undergoing implant therapy. Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on oral anticoagulation therapy following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The oral anticoagulation therapy management strategies as well as the protocols during and after surgery were different. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the oral anticoagulation therapy patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These postoperative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes’s application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies, a thromboembolic event was reported. It was concluded that oral anticoagulation therapy patients (INR 2–4) who do not discontinue the Anticoagulation medication do not have a significantly higher risk of post-operative bleeding than non-oral anticoagulation therapy patients and they also do not have a higher risk of post-operative bleeding than oral anticoagulation therapy patients who discontinue the medication. In patients with oral anticoagulation therapy (INR 2–4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. Oral anticoagulation therapy discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on oral anticoagulation therapy is contraindicated.¹

CONCLUSION

Based on the evidence in review of the dental clinical literature, it can be stated that there is no need to withdraw continuous anticoagulant therapy for nonsurgical or surgical dental procedures if the patient’s anticoagulation level is within the currently recommended therapeutic range,i.e.1.0 to 4.0. If the patient’s anticoagulation level exceeds the therapeutic range,i.e. if the value of INR is greater than 4.0, the physician may recommend withdrawing the anticoagulant therapy or reducing the dosage until the level is within the therapeutic range so that dental surgery can proceed safely. Good surgical technique and appropriate local measures like gelatine sponges with silk sutures; vasoconstrictors in local anaesthetic; systemic, irrigant and mouthrinse forms of tranexamic acid; and atraumatic surgical techniques, to control bleeding are important for all dental patients, especially those receiving continuous anticoagulant therapy. Practitioners should consult with the patient’s physician if necessary to determine his or her most recent INR before dental surgery is performed. Since physicians are not familiar with many dental procedures and their associated bleeding risks, it is important for dentists to educate them and supply data that support or cease the continuation of anticoagulant therapy. Dentists have an obligation to their patients to advise continuation of therapeutic levels of anticoagulation, but if the patient and physician insist, then it should be the physician who withdraws the anticoagulant therapy and the dentist who performs the dentistry.

REFERENCES