Risks and complications

Direct oral anticoagulants (DOAC) are commonly used to treat venous thromboembolism. The main DOACs can be categorised as factor Xa inhibitors: rivaroxaban (Xarelto®), apixaban (Eliquis®), edoxaban (Lixiana®); or as direct thrombin IIa inhibitors: dabigatran (Pradaxa®).

DOACs have obvious pharmacological advantages, such as: predictable and consistent anticoagulant effects, rapid onset/offset of action and low interactions. They have replaced Vitamin K antagonists (VKA) and coumarin anticoagulants in thromboembolic prevention, especially in cases involving atrial fibrillation.

However, DOACs do have associated risks (Shi et al. 2017; Clemm et al. 2016; Yagyuu et al. 2017). Since DOACs started being prescribed widely, an increasing number of bleeding events have been registered in the European database of suspected adverse drug reaction reports. Compared to VKAs, however, DOACs have a lower postoperative risk following implant surgery. Additionally, there is less risk of bleeding associated with implant surgery than with extractions.

“DOACs have obvious pharmacological advantages … However, DOACs do have associated risks”

In order to assess the risk of bleeding events, we should focus on plasma levels following dosage. Plasma concentration levels peak 2–3 hours after the last intake of the medication, and drop to trough levels about 16–24 hours after. This is the period when surgery would be safer.

“Surgery would be safer 16–24 hours after medication intake”

Dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) have especially high renal elimination (over 80% and 60% respectively). But when renal function is impaired, the elimination of DOACs decreases significantly. The maximum plasma level is higher, and trough levels are not reached until around 48 hours later.

“When renal function is impaired, the elimination of DOACs decreases significantly”

The speaker described the ORBIT bleeding score, which is a five-element index validated for assessing the individual bleeding risk of DOACs and for supporting clinical decision making (O’Brien et al. 2015). The ORBIT scoring system includes the following risk contributors, along with their associated score (O’Brien et al. 2015):

• old age (over 75 years of age) [1]
• reduced haemoglobin (Hb) or haematocrit (Hct) or anaemia [2]
• bleeding history [2]
• insufficient kidney function [1]
• treatment with antiplatelets [1]

The higher the score the higher the bleeding risk; the maximum score is 7.

“The higher the score the higher the bleeding risk”

Bleeding risks and preoperative haemostatic control measures are only supported by scientific evidence type III (clinical experience). The current protocol for managing bleeding risks includes careful patient selection and taking appropriate measures according to the expected surgical morbidity (Lanau et al. 2017). The speaker stated that the prevention of bleeding risks involves three elements: invasiveness; anatomical site; medical necessity. The speaker outlined the following factors which should be taken into account to assess risk:

• patient selection: when selecting patients, we should exercise caution with elderly and multimorbid patients, or those with hypertension, a history of bleeding, anaemia, renal impairment, or diabetes
• the pharmacologic risk: drugs influencing the DOAC’s effects, such as: NSAIDs and Azole antimycotics etc. (Forbes & Polasek. 2017). In general, drug interactions are lower, compared with VKAs
• invasiveness of procedure: in simpler and less invasive surgical procedures, it is advisable to keep a minimum time interval (12–24h) between the last dose and the surgical intervention (type II) and to maximise local haemostatic measures (type I)
• discontinuation: in complex surgeries temporary suspension of DOACs may be indicated, but always only having consulted an internist (type I)
• antagonists: antagonists to DOACs are available to stop severe haemorrhages (type II)