Risk of thrombosis-related events and bleeding complications in general and in connection with surgical interventions in dentistry in people taking anticoagulants

About the project

Aim

The overall aim is to study the risk of thrombosis-related events or bleeding complications that lead to emergency hospital visits or death in people taking anticoagulants, if this risk is increased in connection with surgical interventions in dentistry, and if there are differences in risk between different anticoagulants.

Background

Direct oral anticoagulants (DOAC) and vitamin K antagonists such as warfarin are used for the prevention of thrombosis in patients with atrial fibrillation and the treatment of deep vein thrombosis. DOAC was introduced in Sweden in 2008 and today there are several different DOACs on the Swedish market. Apixaban is the most prescribed followed by dabigatran, rivaroxaban and exdoxaban. During treatment with vitamin K antagonists and DOAC, the risk of bleeding increases, especially in connection with surgical interventions. Although it is generally known that bleeding problems associated with surgery are lower for DOACs compared to vitamin K antagonists, the extent and severity of bleeding associated with oral surgery are still unclear. Due to the risk of bleeding, vitamin K antagonists and DOACs are sometimes withdrawn in connection with surgical procedures in dentistry and healthcare. Withdrawal of vitamin K antagonists and DOACs reduces the risk of bleeding but instead contributes to an increased risk of thrombosis. Antiplatelet drugs are used to prevent cardiovascular complications after myocardial infarction and in unstable coronary artery disease and to prevent the recurrence of cerebrovascular disease. To reduce the risk of bleeding, platelet aggregation-inhibiting drugs are sometimes withdrawn in connection with surgical procedures in dentistry and healthcare, but discontinuation also contributes to an increased risk of thrombosis.

Project description

Study I

Impact of direct oral anticoagulants on bleeding tendency and postoperative complications in oral surgery: a systematic review of controlled studies

Aim

To evaluate whether medication with DOAC during oral surgery increases the risk of bleeding and other complications.

Material and method

This systematic literature review will be conducted according to PRISMA Guidelines. Three databases will be used in the literature search and grading of the quality of evidence will be carried out. If appropriate, a meta-analysis will be conducted.

PICO

• Population: Patients undergoing oral surgery
• Intervention: Medication with DOAC with or without discontinuation in connection with the oral surgery procedure
• Control: Medication with anticoagulants other than intervention or no anticoagulants
• Outcome: Postoperative bleeding complication, bleeding volume during procedure, time required for procedure

Study II

Estimation of blood loss associated with maxillofacial surgical treatments by measurement of hemoglobin concentrations in mixtures of blood, saliva and saline: a laboratory study.

Aim

To validate in the laboratory the accuracy of measurements of blood loss in oral surgery using spectrophotometry.

Material and method

To recreate the clinical situation regarding collected fluid from surgical interventions in the oral cavity, several different dilution series consisting of different concentrations of blood, saline and saliva will be analyzed. After each dilution, the hemoglobin concentration (Hb) will be measured with either HemoCue® 201 + or HemoCue Plasma/Low Hb. To calculate the simulated blood loss in each sample, the following formula will be used: Blood loss = (total volume of fluid x Hb in fluid) / (original Hb). Samples without saliva with previously known Hb serve as controls.

Study III

DOAC in oral surgery: impact on bleeding tendency, surgical difficulty and postoperative complications. A controlled prospective non-randomized clinical study.

Aims

• To compare the incidence of bleeding complications during and after oral surgical procedures between patients continuing DOACs and patients continuing warfarin throughout surgery and postoperatively.
• To compare the perioperative bleeding volume during oral surgical procedures between patients continuing DOACs and patients continuing warfarin throughout surgery.
• To examine whether increased perioperative bleeding volume complicates the planned intervention, thereby prolonging the operation time.

Material and method

A multicenter study that will include patients who have been referred to the maxillofacial surgery units at Skåne University Hospital in Helsingborg, Kristianstad and Lund and to the Faculty of Odontology, Malmö University for the extraction of one or more teeth. The primary outcome measure is bleeding complications during the first 7 days after treatment. Secondary outcome measures are bleeding volume during surgical intervention in the oral cavity, treatment difficulty, operative time and other postoperative complications. The outcome measures will be related to the various surgical techniques used in the study.

Study IV

Thromboembolic and bleeding events leading to emergency hospital visits or death for patients taking DOACs compared to patients taking other anticoagulants and patients not taking any anticoagulant.

Aim

To investigate whether the risk of thrombosis-related events or bleeding complications leading to emergency hospital visit or death is elevated for patients taking DOACs compared to patients taking other anticoagulants and patients not taking any anticoagulant.

Material and method

Five cohorts will be included; one cohort exposed to DOACs, one exposed to warfarin, one exposed to thrombocyte aggregation inhibitors, one exposed to low molecular weight heparins and one cohort not medicated with anticoagulants. The persons will be identified by the Swedish National Prescribed Drug Register. All exposed individuals living in Sweden during the study period will be included. The persons in the unexposed cohort will be randomly selected from the Swedish Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA) in the proportions 2:1. The unexposed cohort is matched to the exposed cohort on gender and age.

Significance

The results of these studies can be used to develop a basis for guidelines for how patients on medication with anticoagulants should be cared for in general and in connection with surgical interventions in dentistry.