CLINICAL PHARMACOLOGY (TRANSV)

Master 2017-18
LESSON 3 (20/6/2017): ACTIVITY “NEW ORAL ANTICOAGULANTS”
Name and surname: ____MARIA FERNANDA PAZMIÑO RIVERA ____________________

1. Describe which treatments are proposed (in Costantinides et al., 2016) to manage moderate-
severe bleeding in patients treated with DABIGATRAN during and after dental surgery:

For moderate or severe bleeding, treatments include mechanical compression, surgical

intervention, fluid replacement, hemodynamic support, oral charcoal application (for recent
ingestion of dabigatran) and haemodialysis.

For life-threatening bleeding, treatment includes administration of prothrombin complex

concentrates or charcoal and supportive measures although recent investigations showed no
effect of prothrombin complex concentrates on aPTT, TT and ECT.

Discontinuing anticoagulants, including dabigatran, for elective surgery or invasive procedures

places patients at an increased risk of stroke and, if discontinuation is necessary, dabigatran
should be restarted as soon as possible.

One of the first rules to reduce the risk of bleeding, is to perform the surgical procedures as late
as possible after the most recent assumption of dabigatran. After surgery, local haemostatic
measures such as suturing, gelatine sponge or cellulose mesh, tranexamic acid mouth rinse
(twice daily for 2–5 days) may help in controlling postoperative bleeding

2. Describe which treatments are proposed (in Costantinides et al., 2016) to manage life-
threatening bleeding in patients treated with DABIGATRAN during and after dental invasive
surgery:

Antidote. Only dabigatran: IDARUCIZUMAB intravenosa concentration.

They need important haemostatic interventions (like tissue or vascular sutures, use of pro-
coagulants or reversal agents). Several factors concur in the assessment of bleeding risk and
these are patient-dependent or surgery-dependent.

Additionally, TT or aPTT performed 6 to 12 h prior to surgical treatment can indicate, when

normal, if the anticoagulant effect of dabigatran has resolved. Dabigatran should be restarted
once a stable clot has formed, usually within 24–48 h following surgery, because of the rapid
onset of this drug.
3. Indicate which treatments are proposed (in Costantinides et al., 2016 and in Curto et al., 2017)
to manage life-threatening bleeding in patients treated with RIVAROXABAN during a dental
invasive surgery:

Rivaroxaban has not a specific antidote although some studies suggest the use of recombinant
factor VIIa or active concentrate prothrombin complex to antagonizing the anticoagulant effect

.
A careful monitoring of the entity of bleeding is indicated in these patients especially during and
after surgical dental procedure.

Dental procedures with average and high bleeding risk: These cases require temporary
discontinuation of rivaroxaban. When to discontinue rivaroxaban depends on the patient’s renal
function and the drug’s plasma half-life.

The indications given for dabigatran are also applicable to rivaroxaban. Life-threatening
bleeding, treatment includes administration of prothrombin complex concentrates or charcoal
and supportive measures although recent investigations showed no effect of prothrombin
complex concentrates on aPTT, TT and ECT.

4. Recommendations for the discontinuation of dabigatran/rivaroxaban depending on dental

surgery (Costantinides et al, 2016):

As for dabigatran, the decision of discontinuation has to be carefully discussed with the
patients’s physician to avoid possible thrombo-embolic complications.

4.1. uncomplicated extractions

The most current informations suggest that interruption of rivaroxaban is not

required for simple surgery like dental extraction.
the indications given for dabigatran are also applicable to rivaroxabán.

4.2. oral and maxillofacial surgery

Rivaroxaban should be discontinued at least 24 h before oral and maxillofacial

surgery in patients at risk of excessive bleeding or impaired haemostasis.

Dental procedures with average and high bleeding risk: These cases require
temporary discontinuation of rivaroxaban. When to discontinue rivaroxaban
depends on the patient’s renal function and the drug’s plasma half-life

4.3. patient with severe renal impairment

Patients with severe renal impairment may necessitate a period > 24 h of

discontinuation because they show a significant increase in maximum plasma
concentration and longer half- life of rivaroxaban.
5. After discontinuation, how dabi/riva administration is recommended to be restarted after
surgery (Costantinides et al, 2016)?

When discontinued, rivaroxaban should not be restarted immediately after surgery, but
usually within 24–48 h due to its rapid onset. As for dabigatran, the decision of
discontinuation has to be carefully discussed with the patients’s physician to avoid possible
thrombo-embolic complications.

6. Patient taking dabigatran. In the postoperative phase, an analgesic should be administered.

Which type of analgesic would be more appropriated and why (Costantinides et al, 2016)?

In the postoperative phase, attention has to be paid to the administration of analgesics.

Although dabigatran does not directly interact with NSAIDs, both increase the risk of bleeding.
For this reason, prescription of NSAIDs should be made with caution, preferring alternative
drugs for pain management.
Paracetamol or opioid medications are safer alternatives for patients taking dabigatran.