- Antiplatelet medication
Low-dose aspirin (75mg-300mg daily), clopidogrel (Plavix®), dipyridamole (Persantin®,
Persantin Retard®), aspirin plus dipyridamole (Asasantin Retard®)
Patients taking antiplatelet will have a prolonged bleeding time but this may not be clinically
relevant.
Stopping antiplatelet therapy increases the risk of a stroke or myocardial infarction occurring;
patients are more at risk of permanent disability or death if they stop antiplatelet medication
prior to a surgical procedure than if they continue it.
Bleeding complications, while inconvenient, do not carry the same risks as thromboembolic
complications.
- Patients taking antiplatelet monotherapy
Postoperative bleeding after dental procedures can be controlled using local haemostatic
measures in patients taking antiplatelet monotherapy.
Published reviews of the available literature advise that antiplatelet monotherapy should not
be stopped prior to dental surgical procedures.
- Patients taking antiplatelet dual therapy
The combination of clopidogrel plus aspirin is mainly used in patients with stents. The
combination of aspirin plus dipyridamole is used for the prevention of strokes or TIAs.
Aspirin plus dipyridamole poses a similar bleeding risk as aspirin monotherapy.
There is insufficient evidence to establish to what extent bleeding risk increases if patients
take both aspirin and clopidogrel.
Due to the high risk of thromboembolic events in patients taking aspirin plus clopidogrel they
should not have their antiplatelet medication altered or stopped without consultation with the
interventional cardiologist.
Patients taking aspirin plus clopidogrel may need to be referred to a dental hospital or
hospital-based oral/maxillofacial surgeon.
- How do antiplatelet medications affect clotting?
Platelets provide the initial haemostatic plug at the site of a vascular injury. They are also involved in
pathological processes and are an important contributor to arterial thrombosis leading to myocardial
infarction and ischaemic stroke.
- Available antiplatelet medications include:
Low-dose aspirin (75mg-300mg daily)- Used for the secondary prevention of thrombotic
cardiovascular or cerebrovascular disease and following coronary artery bypass surgery.1 N.B.
Many patients take low-dose aspirin that is recommended, but not prescribed, by their GP. Others
take aspirin of their own accord in the belief that it will offer them cardiovascular protection.
Clopidogrel - Licensed as monotherapy for the prevention of atherothrombotic events in
patients suffering myocardial infarction, ischaemic stroke or peripheral arterial disease and in
conjunction with aspirin for non-ST segment elevation acute coronary syndrome (unstable angina
or non-Q-wave myocardial infarction) and ST segment elevation acute myocardial infarction in
medically treated patients eligible for thrombolytic therapy.2
Clopidogrel is also recommended in combination with low-dose aspirin after the insertion of a
coronary artery stent (unlicensed indication). The combination is used for 4 -12 weeks following
the insertion of a bare metal stent and for 6 – 12 months following the insertion of a drug-eluting
stent (local policies vary).
Dipyridamole - Used as an adjunct to oral anticoagulation for
the prophylaxis of thromboembolism associated with prosthetic heart valves. Modified release
dipyridamole preparations are licensed for the secondary prevention of ischaemic stroke and
transient ischaemic attacks. Asasantin Retard® contains both aspirin and dipyridamole and is
licensed for the secondary prevention of stroke and transient ischaemic attacks.
All antiplatelet medications affect clotting by inhibiting platelet aggregation but they do so by a variety
of different mechanisms. Aspirin irreversibly acetylates cyclooxygenase, inhibiting the production of
thromboxane A2.This results in decreased platelet aggregation by adenosine diphosphate (ADP) and
collagen. Clopidogrel selectively inhibits ADP-induced platelet aggregation. Dipyridamole is an
adenosine reuptake inhibitor and phosphodiesterase inhibitor with antiplatelet and vasodilating
activity.The action of dipyridamole is reversible. Aspirin begins irreversibly inhibiting platelet
aggregation within one hour of ingestion and clopidogrel within two hours; this lasts for the life of the platelets (7-10 days).The effect is only overcome by the manufacture of new platelets. Complete recovery of platelet aggregation may occur in 50% of cases by day three and in 80% of cases by day four.
Aspirin and clopidogrel have a synergistic antiplatelet effect as both affect platelet aggregation by
different mechanisms. There is evidence that the effects of aspirin and dipyridamole on platelet
behaviour are additive however, addition of dipyridamole to acetylsalicylic acid does not increase the
incidence of bleeding events.
Non-steroidal anti-inflammatory drugs (NSAIDs) other than aspirin (e.g. ibuprofen, diclofenac)
have a reversible effect on platelet aggregation and platelet function is restored once the drug is
cleared from the circulation. NSAIDs are not used clinically for their antiplatelet activity.
Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib) do not have any appreciable antiplatelet
activity.
When platelets are inhibited it takes longer for free blood flow from a cut to stop and for primary
haemostasis to occur i.e. the ‘bleeding time’ is prolonged.
- How is bleeding time assessed?
SUMMARY OF EVIDENCE
There is no suitable test available to assess the increased risk of bleeding in patients taking
antiplatelet medications.
Platelet function is commonly assessed using the cutaneous bleeding time test. When platelet function
is normal bleeding time ranges from 2 to 10 minutes depending on the individual and the test
used.This range varies between institutions and depending on the method of measurement
used. Bleeding times may be longer in women than men.
A correlation between bleeding time test results and the rate of surgical bleeding complications has
not been established.One study in 30 healthy patients found no relationship between the cutaneous
bleeding time test and oral bleeding time following a single tooth extraction. The authors concluded
that the cutaneous bleeding time test has no role in the prediction of bleeding in the dental setting.
The cutaneous bleeding time test should not be used to estimate the haemorrhagic risk in a patient on
antiplatelet medication.There is currently no suitable bioassay test sophisticated enough to be used
routinely for the monitoring of side effects associated with antiplatelet medications.
- How do antiplatelet medications affect bleeding time?
All patients receiving antiplatelet medications must be considered to have drug-induced altered
platelet function. However, the effect on primary haemostasis is minimal when antiplatelet agents are used as monotherapy in patients without additional risk factors for impaired clotting.There will be an increased bleeding tendency if two antiplatelet agents are used in combination.Aspirin can double the baseline bleeding time but this may still be within or just outside the normal range. It has been
reported that only 20% to 25% of patients using aspirin have an abnormal bleeding time. Clopidogrel
is considered a more potent antiplatelet agent and can prolong the bleeding time by 1.5 to 3 times
normal.Sensitivity to antiplatelet agents varies from one person to another.
A small study has assessed the effect of cessation of low-dose aspirin on bleeding time in healthy
volunteers.Baseline bleeding times were measured using a standardised method (manufacturer’s
range of normal bleeding times 2 to 10 minutes). Volunteers were then randomly assigned to one of
three treatment groups; placebo, aspirin 75mg or aspirin 300mg daily. Treatment was taken for 14
days. Once the aspirin or placebo was stopped bleeding time was measured on a daily basis until it
returned to baseline; mean prolongation of bleeding time was also calculated. Mean bleeding time at
baseline was between 2 and 10 minutes for all participants. At 24 hours after cessation of treatment
the mean prolongation of bleeding time was 22 seconds for patients on placebo, 105 seconds for
those on 75mg aspirin and 211 seconds for those on 300mg aspirin. The mean bleeding time for
participants who took 75mg aspirin was under 10 minutes at 24 hours after cessation. There was
considerable variability among individuals on aspirin as to when haemostatic function returned to
baseline. However, all bleeding times had returned to baseline values by the sixth day.
- What are the thromboembolic risks associated with stopping antiplatelet
medications in the perioperative period?
SUMMARY OF EVIDENCE
Stroke and myocardial infarction have been associated with cessation of antiplatelet medication
approximately 10 days before the event.
Stopping aspirin prior to surgical procedures may increase the risk of thromboembolic events by
0.005%.
Thromboembolic events associated with the cessation of antiplatelet medications have only recently
been identified. One of the first papers to be published describing this association was a retrospective
analysis of 475 patients admitted to hospital with a myocardial infarction; 11 (2.3%) had discontinued
aspirin therapy within 15 days prior to admission. 20 Nine patients discontinued aspirin prior to planned
surgical procedures, one of which was a dental procedure. The dental patient had been stable and
symptom free on aspirin for 10 years but suffered a myocardial infarction 10 days after stopping
aspirin therapy.
The same author has now published a prospective cohort study of 1,358 consecutive patients
admitted to hospital with acute coronary syndromes.It was found that 5% of the patients had
recently (11.9 ± 0.8 days before admission) stopped oral antiplatelet agents. Two thirds of the patients
who had stopped oral antiplatelet agents had done so for planned surgery. Patients who had recently
withdrawn from oral antiplatelet agents were characterised by catastrophic outcomes with a 2-fold
increase in the rate of death compared with prior users or nonusers. In addition bleeding
complications in this group were unusually high and were significantly linked to ischaemic events. The
study conclusion was that these observations support the hypothesis of a rebound effect after oral
antiplatelet medication interruption.
Another prospective cohort study examined the incidence of aspirin withdrawal in 1,236 patients
admitted to hospital for acute coronary syndrome. Fifty-one new coronary events occurred less than
one month after aspirin withdrawal and represented 4.1% of all patients hospitalised for a coronary
event but 13.3% of those who relapsed. The mean delay between aspirin withdrawal and acute
coronary event was 10 ± 1.9 days (range 4 to 17 days). Thirteen (25.5%) of the patients who
discontinued their aspirin medication did so prior to dental treatment.
A retrospective case-control study assessed the discontinuation of aspirin as a risk factor for
ischaemic stroke.In the study period 309 patients who were receiving aspirin, either as
monotherapy or with another antithrombotic drug, prior to the event were admitted with ischaemic
stroke or transient ischaemic attack. Cases were matched with controls who had a history of stroke
but had not had a stroke within the last six months and who were taking long-term aspirin for
secondary prevention. Thirteen patients (4.2%) had discontinued aspirin therapy in the four weeks
prior to the event compared to four controls (1.3%). The mean interval between treatment disruption
and cerebral infarction in the patient group was 9.5 ± 7 days.
Thromboembolic events were reported in two patients following the withdrawal of antiplatelet
medication one week prior to cutaneous surgery and in five patients (two died) following withdrawal
of aspirin 8 to 10 days prior to transurethral prostatectomy.
A review and meta-analysis of the cardiovascular risks of use versus perioperative withdrawal of low-
dose aspirin found that in 93 patients who presented with acute vascular syndromes after cessation of
low-dose aspirin (15.1%) had discontinued it due to dental surgery. The time interval between
aspirin discontinuation and the acute vascular event was 8.5 ± 3.6 days for acute coronary syndrome,
14.3 ± 11.3 days for acute cerebral events and 25.8 ± 18.1 days for acute peripheral vascular events.
A further review and meta-analysis of 50,279 patients at risk for coronary artery disease assessed the
hazards associated with discontinuing or not adhering to aspirin therapy and concluded that aspirin
withdrawal has a major detrimental effect regardless of the indication for its use.The analysis found
that the typical average interval from aspirin cessation to thromboembolic event was 10 days.
Estimation of the risk associated with stopping antiplatelet therapy has been attempted. One author
estimated that the risk of thromboembolic events associated with the withdrawal of aspirin for 3 to 14
days prior to cutaneous surgery is about 0.005% (1 thromboembolic event in every 21,448 cutaneous
excisions).Another review uses the estimate that the background rate of cardiovascular events is
about 1.4 per 1,000 patients per week; administration of low-dose aspirin reduces this rate to 1.1
events per 1,000 patients per week. Therefore withholding aspirin perioperatively for 7 days would add
a risk of about 0.3 additional events for every 1,000 patients per week. However, the review suggests
that a rebound hypercoagulable state may occur when low-dose aspirin is stopped resulting in an
increase in the cardiovascular risk to 11 events per 1,000 patients per week immediately following
withdrawal.
- What are the risks of bleeding associated with continuing antiplatelet
medications in the perioperative period?
SUMMARY OF EVIDENCE
Patients taking antiplatelet medications will have a prolonged bleeding time but this may not be
clinically relevant.
Postoperative bleeding after dental procedures can be controlled using local haemostatic
measures in patients taking antiplatelet monotherapy.
There is insufficient evidence to comment on the bleeding risk if patients take both aspirin and
clopidogrel.
Clinically significant postoperative bleeding following dental procedures has been defined28 as that
which:
1. continues beyond 12 hours
2. causes the patient to call or return to the dental practice or accident and emergency department
3. results in the development of a large haematoma or ecchymosis within the oral soft tissues
4. requires a blood transfusion.
Patients with underlying hepatic, renal or bone marrow disorders often have disease related bleeding
disorders. Bleeding risk also increases with age and with heavy alcohol consumption.
Two small prospective studies have investigated the effect of continuing low-dose aspirin therapy in
patients undergoing dental procedures. One prospectively studied 51 consecutive patients on long-
term low-dose aspirin therapy scheduled for oral surgery.Aspirin was not stopped. All patients had
bleeding times measured preoperatively; the mean bleeding time was 2.86 ± 0.54 minutes. All surgery
was performed on an outpatient basis under local anaesthetic. In only one case (third molar surgery)
was introperative bleeding considered excessive; applying pressure for 10 minutes with gauze soaked
in 1% feracrylum solution (a haemostatic polymer of polyacrylic acid) controlled this. In all other cases
a simple pressure pack and suturing produced haemostasis. No postoperative bleeding was reported
in any case at planned follow up visits over two weeks.
The second study investigated stopping versus continuing low-dose aspirin prior to dental extraction.
Thirty-nine patients taking aspirin 100mg daily were studied. Nineteen continued aspirin as normal
and 20 stopped aspirin seven days prior to the planned extraction(s). A bleeding time test was
performed one hour prior to the procedure. The mean bleeding time was longer in patients who
continued aspirin compared to those who stopped (3.1 mins vs. 1.8 mins, p=0.004). Although the
difference was statistically significant, none of the patients who continued aspirin had a bleeding time
outside the normal range (1-4.5 minutes in this study). Intraoperative bleeding was controlled in 33
(85%) patients with gauze packing and sutures. Six patients (two who stopped aspirin and four who
continued aspirin) had tranexamic acid added to the local packing. No patient experienced
uncontrolled bleeding immediately postoperatively or in the following week.
A prospective study of 253 patients (41 taking aspirin, 212 not taking aspirin) undergoing cutaneous
surgery found bleeding was easily controlled in all patients. There was no significant difference
between the two groups in terms of postoperative complications.
There are few published studies on the relative risks of perioperative bleeding with clopidogrel and
dipyridamole. The pharmacological mechanisms underlying the antiplatelet action of clopidogrel and dipyridamole suggest that patients taking these medications as monotherapy will be at no greater risk of excessive bleeding than those taking aspirin. Patients on either clopidogrel or dipyridamole as monotherapy should not have their therapy stopped or altered before dental procedures.
Dual antiplatelet therapy
Combined use of aspirin and clopidogrel produces additive and possible synergistic effects as the two
block complementary pathways in the platelet aggregation cascade.The use of this combination is
increasing in patients with acute coronary syndrome, in ST segment elevation acute myocardial
infarction and in patients who have had coronary artery stents (bare metal stents (BMS), drug eluting
stents (DES)) inserted. Patients with stents are at high risk of thromboembolic events and it has been found that the greatest risk for stent thrombosis is premature discontinuation of clopidogrel therefore it is recommended that antiplatelet therapy should not be stopped at any time, but especially within the first 6 -12 months after DES insertion or the first 6-12 weeks after BMS insertion, without discussion with an interventional cardiologist. There is insufficient evidence to comment on the bleeding risk if patients take both aspirin and clopidogrel. These patients may need to be referred to a dental hospital or hospital-based oral/maxillofacial surgeon.
The use of aspirin in combination with dipyridamole does not increase the risk of bleeding.
NSAIDs other than aspirin e.g. ibuprofen, diclofenac, also have antiplatelet activity and may increase bleeding time. However, this rarely exceeds normal limits. Even major surgery is not usually complicated by patients taking NSAIDs and they should not be discontinued prior to dental surgical procedures.
- How do the risks of thromboembolic events and postoperative bleeding
balance?
SUMMARY OF EVIDENCE
Bleeding complications, while inconvenient, do not carry the same risks as thromboembolic
complications.
Patients are more at risk of permanent disability or death if they stop antiplatelet medication prior
to a surgical procedure than if they continue it.
Published reviews of the available literature advise that antiplatelet monotherapy should not be
Published reviews of the available literature advise that antiplatelet monotherapy should not be
stopped prior to dental surgical procedures.
There is insufficient evidence to comment if patients take both aspirin and clopidogrel.
Thromboembolic events, including fatalities, have been reported after antiplatelet therapy withdrawal.
Although the risk is low, the outcome is serious. This must be balanced against the fact that there is
no single report of uncontrollable bleeding when dental procedures have been performed without
stopping antiplatelet medications.
A meta-analysis and review has examined the cardiovascular risks associated with the perioperative
withdrawal of low-dose aspirin versus the bleeding risks associated with its continuation. The meta-
analysis examined bleeding risk associated with any surgical procedure and found that although
aspirin increases the frequency of bleeding complications by approximately 50%, however, surgeons
who were blinded to the aspirin status of the patient could not differentiate patients taking aspirin from
those not taking aspirin. In addition although low-dose aspirin increases bleeding quantitatively it does
not move the bleeding complications towards a higher risk category. Thus, in most cases bleeding
complications can be handled in the same way as they would be without the influence of aspirin.
When assessing the risk of stopping aspirin the meta-analysis showed that discontinuation of low-
dose aspirin resulted in hazardous events such as stroke, myocardial infarction or cardiovascular
death. Quantifying the incidence of cardiovascular events after aspirin withdrawal was not possible as
the retrospective studies included in the meta-analysis did not report the number of patients who did
not suffer a cardiovascular event despite aspirin withdrawal. The authors concluded that aspirin
should only be discontinued perioperatively if the assessed perioperative bleeding risks are expected
to be similar to, or exceed, the observed cardiovascular risks after stopping aspirin.
Should the decision on whether to stop or continue antiplatelet therapy prior to dental surgery be
made on a case-by-case basis? This is an attractive option but impractical and potentially dangerous.
Even conferring with the prescriber of the antiplatelet medication is unlikely to help as most will be
unaware of the haemostatic risks of the planned dental procedures.
A guidance document produced in 2001 advised that antiplatelet medications should only be
discontinued in the perioperative period when the haemorrhagic risk of continuing them is definitely
greater than the cardiovascular risk associated with their discontinuation. This advice has been
strengthened by the conclusions of recently published reviews.
Consensus is that for minor surgical procedures, including dental procedures, antiplatelet medications
used as monotherapy should not be stopped or doses altered and that local haemostatic measures
are used to control bleeding When patients are taking dual antiplatelet
therapy either their interventional cardiologist should be contacted for advice or the patient should be
referred to a dental hospital or hospital-based oral/maxillofacial surgeon.
Which patients taking antiplatelet medication should not undergo surgical
procedures in primary care?
Patients taking antiplatelet medications with the following medical problems should not be treated in
primary care without medical advice or should be referred to a dental hospital or hospital based dental
clinic:
• liver impairment and/or alcoholism
• renal failure
• thrombocytopenia, haemophilia or other disorder of haemostasis
• currently receiving a course of cytotoxic medication
• dual antiplatelet therapy.
For which procedures can antiplatelet medications be safely continued?
Minor surgical procedures can be safely carried out without altering the antiplatelet medication dose.
Those likely to be carried out in primary care will be classified as minor e.g. simple extraction of up to three teeth, gingival surgery, crown and bridge procedures, dental scaling and the surgical removal of teeth.
When more than three teeth need to be extracted multiple visits will be required. The extractions may be planned to remove two to three teeth at a time, by quadrants, or singly at separate visits.
Scaling and gingival surgery should initially be restricted to a limited area to assess if bleeding is
problematic.
- How should the risk of bleeding be managed?
Timing
Think about the timing of the surgery. Planned surgery should ideally be:
• At the beginning of the day - this allows more time to deal with immediate re-bleeding problems.
• Early in the week - this allows for delayed re-bleeding episodes occurring after 24–48 hours to be
dealt with during the working week.37
Local anaesthetic
A local anaesthetic containing a vasoconstrictor should be administered by infiltration or by
intraligamentary injection wherever practical. Regional nerve blocks should be avoided where
possible. However, if there is no alternative, the local anaesthetic should be administered cautiously
using an aspirating syringe. Local vasoconstriction may be encouraged by infiltrating a small amount
of local anaesthetic containing adrenaline (epinephrine) close to the site of surgery.
Local haemostasis
Efforts should be made to make the procedure as atraumatic as possible and any bleeding should be
managed using local measures.
Sockets should be gently packed with an absorbable haemostatic dressinge.g. oxidised
cellulose (Surgicel®), collagen sponge (Haemocollagen®) or resorbable gelatin sponge (Spongostan®)
then carefully sutured. Resorbable sutures are preferable as they attract less plaque. If non-
resorbable sutures are used they should be removed after 4-7 days. Following closure, pressure
should be applied to the socket(s) by using a gauze pad that the patient bites down on for 15 to 30
minutes.
Patients should be given clear instructions on the management of the clot in the postoperative period
and advised:
• to look after the initial clot by resting while the local anaesthetic wears off and the clot fully forms
(2-3 hours),
• to avoid rinsing the mouth for 24 hours,
• not to suck hard or disturb the socket with the tongue or any foreign object,
• to avoid hot liquids and hard foods for the rest of the day,
• to avoid chewing on the affected side until it is clear that a stable clot has formed. Care should
then be taken to avoid dislodging the clot,
• if bleeding continues or restarts, to apply pressure over the socket using a folded clean
handkerchief or gauze pad. Place the pad over the socket and bite down firmly for 20 minutes. If
bleeding does not stop, the dentist should be contacted; repacking and resuturing of the socket
may be required.
• Who to contact if they have excessive or prolonged postoperative bleeding. The surgery and out
of hours/on call dentist’s name/number should be provided. There should be a facility for the
patient to be reviewed and treated immediately by a dentist if a bleeding problem occurs. If it is not
possible for the patient to be seen immediately by a dentist then the patient should be referred to
their local accident and emergency department.
• On pain control (see below).
How should postoperative pain be managed?
Generally paracetamol is considered a safe over-the-counter analgesic for patients taking antiplatelet medications and it may be taken in normal doses if pain control is needed and no contraindication exists. Aspirin at analgesic doses and non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibuprofen are considered less safe and should be avoided if possible (see interactions below).
If analgesia is to be prescribed, additional options to paracetamol include:
• Dihydrocodeine – an opioid analgesic with similar analgesic efficacy to codeine. Its use should
be considered second line. It is suitable for mild to moderate pain but has no anti-inflammatory
activity and is of limited value in pain of dental origin.
- Are there any drug interactions that are relevant to this patient group
undergoing dental surgical procedures?
NSAIDs should be used with caution in combination with aspirin or clopidogrel. They can damage the lining of the gastro-intestinal tract leading to bleeding that may be worsened by aspirin or
clopidogrel.Analgesic effect of aspirin and paracetamol are additive.
Dipyridamole appears not to interact with NSAIDs.
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