BJD

R EV IE W AR TI C LE British Journal of Dermatology

Perioperative management of and recommendations for

antithrombotic medications in dermatological surgery
I. Palamaras1 and K. Semkova2
1
Department of Dermatology, Barnet General Hospital, Royal Free Foundation Trust, Wellhouse Lane, Barnet, EN5 3DJ London, U.K.
2
Department of Dermatology and Venereology, Medical University-Sofia, Sofia, Bulgaria

Summary

Correspondence With the ever-increasing number of patients on anticoagulant or antiplatelet

Ioulios Palamaras. medications presenting for a dermatological surgical procedure, dermatological
E-mail: drioulios@hotmail.com
surgeons are facing the challenge of managing these drugs in order to balance
Accepted for publication the bleeding complications against the risk of thromboembolic events. The diffi-
15 August 2014 culty arises from the scarce available recommendations, the data in the literature
that is in part contradictory and the rate of emergence of newer agents that have
Funding sources not been thoroughly studied and widely used. Although the common approach
No external funding. in the past was to stop any antithrombotic medications, including warfarin and
aspirin, several days prior to cutaneous surgery, recent data suggest that this
Conflicts of interest
None declared.
practice should be changed as the relatively low risk of bleeding does not justify
the life-threatening nature of a likely thrombosis. For patients on warfarin, sur-
DOI 10.1111/bjd.13362 gery should be avoided if the international normalized ratio is > 3
5; aspirin
should not be stopped prior to dermatological surgery and in most other circum-
stances patients taking long-term antithrombotic medication should not stop this
prior to dermatological surgery. In more complicated cases liaison with the pre-
scriber is indispensable even when the therapy should be discontinued for a short
period of time. This review studies the available data and presents the dermato-
logical surgeon with up-to-date information about all studies concerning the old
and new antithrombotic agents in the setting of dermatological surgery proce-
dures. Our aim is to propose our recommendations based on the most recent
evidence and our experience and provide a comprehensive approach to the der-
matological surgeon without excluding the need for individual assessment of
each case.

What’s already known about this topic?

• The number of patients on antithrombotic medications undergoing cutaneous sur-
gery is steadily increasing.
• There are no strict guidelines on perioperative management of these agents and the
data on bleeding complications is contradictory.

What does this study add?

• This study provides an up-to-date comprehensive approach to the management of
antithrombotic medications in patients undergoing cutaneous surgery.
• The available data on warfarin, aspirin and clopidogrel is sufficient to recommend
that these medications be continued throughout cutaneous surgical procedures.
• The risk of bleeding complications in patients on antithrombotic medications can
be minimized by meticulous surgical techniques, elaborate haemostasis, pressure
dressings and close postoperative follow-up.

© 2014 British Association of Dermatologists British Journal of Dermatology (2015) 172, pp597–605 597
598 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova
Dermatological surgery encompasses a wide variety of proce-
dures of variable interventional extent such as punch and
shave biopsies, standard conventional excisions and Mohs’
micrographic surgery (MMS). About 50% of patients who
present for a dermatological surgical procedure are on one or
more anticoagulant or antiplatelet medications.1,2
The main concern of antithrombotic medications is the
increased risk of bleeding complications during both the pro-
cedure and the recovery period. However, discontinuing the
antiplatelet or anticoagulant agents could result in potentially
life-threatening adverse events.
Although the accepted approach in the past was to stop any
antithrombotic medications several days prior to cutaneous
surgery, recent data suggest that this practice should be chan-
ged as the relatively low risk of bleeding does not justify the
life-threatening nature of a likely thrombosis. The emerging
evidence from other specialties, including ophthalmology,
dentistry, orthopaedics, cardiothoracic and general surgery
encourages the monitored continuation of antithrombotics
during minor surgical procedures.3–6
To date, available detailed recommendations for cutaneous
surgery are scarce and in part contradictory.1,2,7–13 In addi-
tion, newer agents are emerging and the dermatological sur-
geon is challenged to manage drugs that have not been
thoroughly studied and widely used. In such cases liaison with
the prescriber of the antithrombotic proves to be indispensable
even when stopping the therapy for a short period of time.
Our aim with this review was to study the available data
and present the dermatological surgeon with up-to-date infor-
mation about all studies concerning the old and new anti-
thrombotic agents in the setting of cutaneous surgery
procedures. Our recommendations are based on the most
recent evidence and our personal experience and aim to pro-
vide a comprehensive approach without excluding the need
for individual assessment of each case (Table 1).
Materials and methods
The purpose of this study was to review the published data on
antithrombotic medication management in dermatological sur-
gery and to design recommendations for such management on
the basis of the available data and our personal experience. A
systematic review or meta-analysis were not attempted due to
the scarce number of studies for most of the agents.
PubMed and Medline were searched with the terms ‘antico-
agulation/anticoagulants/antithrombotic’ and ‘dermatologic/
skin surgery’. Additionally, articles on each antithrombotic
agent were retrieved by searching for the combination of the
agent’s name and the term ‘dermatologic/skin surgery’.
Antithrombotic medications
Antithrombotic medications are subdivided into two classes:
antiplatelet agents and anticoagulant agents. Antiplatelet drugs
block platelet activation and aggregation with no effect on
fibrin, whereas anticoagulants inhibit thrombin generation and
British Journal of Dermatology (2015) 172, pp597–605
fibrin formation. The action of anticoagulants can be reversed
should severe bleeding occur during or after the procedure,
unlike antiplatelet agents, which remain active for the lifetime
of the platelet.
Anticoagulants
Vitamin K antagonists (warfarin, acenocoumarol,
phenindione)
Vitamin K antagonists are a group of anticoagulants that exert
their effect through depletion of the active form of vitamin K
with subsequent inhibition of the synthesis of vitamin
K-dependent clotting factors (factors II, VII, IX and X). Warfa-
rin is the most widely prescribed agent from this group and
the most common oral anticoagulant in the U.K. Acenocouma-
rol and phenindione are also licensed in the U.K., albeit only
rarely prescribed.
Warfarin is indicated for prophylaxis of systemic embolism
in patients with rheumatic heart disease and atrial fibrillation
(AF), prophylaxis after insertion of prosthetic heart valves
(mechanical heart valves, MHV), prophylaxis and treatment of
venous thromboembolism (VTE) and pulmonary embolism
(PE) and for the management of transient cerebral ischaemic
attacks (TIA).
Warfarin inhibits the activity of vitamin K-dependent coag-
ulation proteins and hinders the formation of a fibrin clot.7
However, primary haemostasis is intact as platelet aggregation
and vasoconstriction are unimpaired. Bleeding complications
should be therefore expected several days postoperatively
when the platelet plugs disperse without the formation of a
stable clot. This warrants close patient supervision in the post-
operative period regardless of the extent of bleeding during
surgery.6,7,10,11,14–17
In a retrospective study of 127 patients, mild bleeding com-
plications were recorded in eight of 26 patients (30%) who
continued warfarin compared with five of 101 patients (5%)
who stopped treatment at least 3 days before surgery. These
did not affect the final surgical outcome.7
In a cohort study of 2394 patients with skin cancer excision
procedures, Dixon et al.15 evaluated 320 patients on warfarin
therapy. Patients with international normalized ratio (INR)
above 3
0 were excluded from the study. Warfarin was an
independent risk factor conferring a 2
9 times increased likeli-
hood for bleeding with bleeding events observed in 2
5% of
all patients on warfarin compared with an overall rate of
0
7%. Very few of these events required wound exploration
and none was life- or function-threatening.
In another study comparing 16 patients on warfarin with
77 controls undergoing dermatological surgery, Alcalay14 did
not observe any significant increase in the intra- or periopera-
tive bleeding given the INR of the patients was within the
range 2–3
5.
Lewis et al.10 performed a meta-analysis of pooled data from
several studies (1373 patients, 1966–2005), including patients
undergoing cutaneous surgery while on warfarin. They esti-
© 2014 British Association of Dermatologists
 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova 599

Table 1 Summary of our recommendations for patients on antithrombotic medications before skin surgery

Drug Recommendations for cutaneous surgery Comments

Warfarin Discontinuation of warfarin for cutaneous surgery is If warfarin is to be stopped:
not recommended Consult prescriber first
Caution is advised when warfarin therapy is Stop it 4–5 days prior to surgery
concomitant with other established independent risk Resume warfarin, at the regular dose, the evening of
factors for bleeding, such as age 67 years or older, surgery or the next day provided the INR is checked
surgery on or around the ear and eyes and closure with on the day of surgery and adequate haemostasis
a skin flap or graft ensured
Advise patient to inform the Warfarin clinic that you Consider preoperative bridging with LMWH for
have surgery planned and the INR should be ≤ 3
5 and high-risk patients
the Warfarin clinic will adjust the dose
INR ≤ 3
5: proceed with surgery
INR > 3
5: avoid surgery
Inform patient of the increased likelihood of
postoperative bleeding especially around the eyes
Major bleeding: use four-factor prothrombin
concentrate and intravenous vitamin K
LMWH Continue LMWH throughout the surgery Data from dermatological surgery is scarce, but
evidence from other specialties shows minimal risk
of bleeding
Direct thrombin Continue with the procedure Data is still scarce
inhibitors: dabigatran If dabigatran is to be stopped:
Consult prescriber first
Stop it 24–48 h before the procedure
Resume dabigatran right after adequate haemostasis
is achieved
Factor Xa inhibitors: Fondaparinux: postpone surgery until discontinuation Data on these agents is still scarce
fondaparinux, or until establishment of oral anticoagulation Although continuation of therapy seems
danaparoid, rivaroxaban, Danaparoid: postpone surgery until discontinuation safer than cessation, elective skin
apixaban Rivaroxaban and apixaban: consult prescriber procedures are better postponed for
after completion of antithrombotic therapy
Aspirin Aspirin should not be discontinued prior to Longer haemostasis during surgery may be required
dermatological surgery in high-risk patientsa
Stop aspirin 7–10 days prior to surgery if taken for
pain-relief or self-prescribed
NSAIDs (nonselective) Continue treatment
Thienopyridines: Clopidogrel (high-risk patientsa): continue clopidogrel
clopidogrel, prasugrel with meticulous haemostasis and careful follow-up
Clopidogrel (low-risk patients): consider withdrawing
clopidogrel 7 days prior to surgery while continuing
aspirin or with the addition of an NSAID in patients
who are not taking aspirin
Prasugrel: consult the prescriber
Dipyridamole Continue treatment

INR, international normalized ratio; LMWH, low molecular weight heparin; NSAID, nonsteroidal anti-inflammatory drugs. aHigh-risk patients
are defined as patients with history of cerebrovascular disease, cardiac surgery, unstable angina, coronary stenting.

mated the risk for moderate to severe postoperative compli-
cations to be 6
7 times higher compared with controls.10
Additionally, the overall reported frequency of postoperative
complications among patients on warfarin was 28
7% vs.
6
5% for the control population, with mild, moderate and
severe complications being 16
4%, 6
6% and 5
7%, respec-
tively.
Data from other interventional procedures, including dental
interventions, arthrocentesis, cataract surgery and endoscopy,
also supports the evidence that perioperative warfarin is not
associated with major bleeding.4,5
Most authors recommend that surgery be performed with-
out discontinuation of warfarin when the values of INR are
within the normal target range (≤ 3
5), although there are no
formal studies to establish the optimal INR in this setting.
Moreover, it is not known whether the bleeding tendency
increases proportionally to the INR across these values.11
In a prospective study of 16 patients undergoing conven-
tional and MMS excisions, Alcalay14 registered no difference
between the control group and the group on warfarin with a
perioperative INR of 1
5–3
48. Ah-Weng et al.6 validated a safe
INR upper limit of 3
5 for dermatological surgery. The

© 2014 British Association of Dermatologists British Journal of Dermatology (2015) 172, pp597–605
600 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova
authors also proposed INR monitoring 24 h prior to surgery
on the basis of their experience, as an interval close to the
time of the procedure allows for a greater confidence.6 In
contrast, in a prospective study by Blasdale and Lawrence16 of
65 patients on warfarin undergoing excision of 70 tumours,
the bleeding risk could not be correlated with INR and it was
demonstrated that the risk of postoperative bleeding was still
increased regardless of INR being within the normal range.
Strict postoperative follow-up and reversal of anticoagula-
tion is warranted in case of major bleeding. Current guidelines
advise emergency anticoagulation reversal with four-factor
prothrombin concentrate and vitamin K intravenously.18
Minor bleeding could be managed with intravenous vitamin K
alone.18
The risk of stopping warfarin depends on the disease that is
being treated. Serious vascular complications have been
reported after cessation of warfarin for dermatological surgical
procedures,19–21 including thromboembolic events and stroke.
Of note, the reported rates of thromboembolic episodes fol-
lowing warfarin discontinuation for other types of surgery
range from 5
8% up to 47%.20
Bridging with low molecular weight heparin (LMWH) is
now recommended to reduce the likelihood of thromboem-
bolism should there be an indication for perioperative cessa-
tion of warfarin.8,18 The bleeding risk with this therapy
depends primarily on the type and extent of procedure, with
reported incidence of major bleeding ranging from 0% for
minor surgery such as skin or dental, 0
7% for invasive proce-
dures such as colonoscopy and 20% for major surgery such as
joint replacement.22
Recommendations
Discontinuation of warfarin for cutaneous surgery is not rec-
ommended based on the available evidence, as the risk of seri-
ous thromboembolic events outweighs the risk of bleeding
complications.
Caution is advised when other established independent risk
factors for bleeding exist while on warfarin, namely, age
67 years or older, surgery on or around the ear and eyes and
complex closure with a skin flap or graft.11,15
If warfarin needs to be stopped, this should be done 4–5 days
prior to surgery.11,18 Warfarin can be resumed, at the regular
dose, the evening of surgery or the next day provided the INR is
checked on the day of surgery according to the latest British
guidelines on warfarin administration and adequate haemostasis
is ensured.18 Preoperative bridging with LMWH should be con-
sidered for high-risk patients with a VTE within the previous
3 months, patients with AF and previous stroke or TIA or multi-
ple other risk factors, and patients with a mitral MHV.18
Indirect thrombin inhibitors (heparin, enoxaparin,
dalteparin)
Indirect thrombin inhibitors licensed for use in Europe include
unfractionated heparin and the LMWHs, enoxaparin and
British Journal of Dermatology (2015) 172, pp597–605
dalteparin. They activate antithrombin through a conforma-
tional change in its reactive site loop, thus potentiating Factor
Xa inhibition. Unfractionated heparin, enoxaparin and daltepa-
rin are approved for the prophylaxis and treatment of throm-
boembolic disorders such as deep vein thrombosis (DVT),
acute arterial embolism or thrombosis, thrombophlebitis, pul-
monary embolism, fat embolism and for the prevention of
clotting in the extracorporeal circuit during haemodialysis. In
addition LMWHs are also used in unstable angina and non-Q-
wave myocardial infarction. Heparin is used primarily in a
hospital setting and its management is hence not relevant to
outpatient cutaneous surgery procedures.
Low molecular weight heparins are usually administered
subcutaneously and are sometimes used as warfarin replace-
ment in the outpatient setting. Reports on bleeding complica-
tions in patients on LMWH undergoing cutaneous surgery are
lacking. This might be due either to the low number of
patients on this particular therapy or to the beneficial safety
profile. LMWH, administered before coronary bypass surgery
in 21 patients, did not increase the postoperative bleeding or
blood products transfusions.23 However, the data in gynaecol-
ogy patients are contradictory with some authors observing
increased risk of postpartum vaginal bleeding after normal
delivery24 while others not.25 The relevance of these data to
dermatological procedures is not clear, but it could be specu-
lated that minor surgery should not be associated with a
higher incidence of bleeding complications given the reported
safety of LMWH in major surgery. Moreover, bridging with
LMWH is already the recommendation by the available current
guidelines to balance the risk of thromboembolism against the
risk of bleeding in high-risk patients who stop warfarin to
have a surgical procedure.18,22
Recommendations
Besides the scarce data, we believe that discontinuation of
indirect thrombin inhibitors is not recommended, as it might
confer a serious risk of thromboembolic events, whereas the
reported risk of bleeding is minimal.
Direct thrombin inhibitors (dabigatran, argatroban)
Direct thrombin inhibitors (DTIs) have been developed in
response to the need for an easier way to manage and con-
trol coagulation, as an alternative to heparins and vitamin K
inhibitors. They bind directly to thrombin without the need
for a co-factor like antithrombin. DTIs do not bind to other
plasma proteins and have a more predictable anticoagulant
effect compared with heparins, have an antiplatelet effect
and do not induce immune-mediated thrombocytopenia.26
Dabigatran and argatroban are the most studied and used in
practice. Argatroban is used for intravenous anticoagulation
in adult patients with heparin-induced thrombocytopenia
type II and is highly unlikely to be an issue in the periop-
erative management of patients scheduled for cutaneous
surgery.
© 2014 British Association of Dermatologists
 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova 601
Dabigatran is an oral anticoagulant with a tendency to be
used as a substitute for warfarin in some patient populations.
Its advantages over warfarin include minimal drug interac-
tions, no genetic metabolism variations, predictable pharmaco-
kinetic and pharmacodynamic profiles, lower risk of
intracranial bleeding and stroke and no need for strict drug
monitoring as is the case with warfarin. The approved indica-
tions of dabigatran include primary prevention of VTE events
in adult patients who have undergone elective total hip
replacement surgery or total knee replacement surgery, and
prevention of stroke and systemic embolism in adult patients
with nonvalvular atrial fibrillation. The experience of dermato-
logical surgeons with dabigatran is somewhat limited. A case
of haematoma after melanoma excision has been reported, but
the authors would still endorse continuation of the dabigatran
therapy.27 A randomized study on periprocedural bleeding
and thromboembolic events in patients undergoing invasive
procedures did not find statistically significant differences in
the incidence of adverse events when comparing background
dabigatran with background warfarin therapy.28 Dabigatran
was discontinued approximately 49 h prior to the procedure
and resumed once adequate haemostasis was achieved. Bleed-
ing rates were evaluated from 7 days before until 30 days
after the surgery and types of procedure were variable [includ-
ing pacemaker/defibrillator insertion (10
3%), dental proce-
dures (10
0%), diagnostic procedures (10
0%), cataract
removal (9
3%), colonoscopy (8
6%) and joint replacement
(6
2%)]. Periprocedural bridging with intravenous heparin or
LMWH was used in 15–17% of patients assigned to dabigatran
and 28
5% of patients assigned to warfarin (P < 0
001).
The main concern with dabigatran is that, unlike warfarin,
it has no antidote and the management of potential bleeding
is more challenging. However, dabigatran has a short half-life
(12–14 h), which facilitates rapid haemostasis restoration and
minimizes the need for antidote application.26 Additionally,
the short half-life allows dabigatran to be discontinued in
many patients no earlier than 24–48 h before the procedure,
thus minimizing the risk of thromboembolic complications
and the complications of heparin bridging.28
Recommendations
Given the available data from other procedures and its com-
parison with warfarin, we suggest that it is better to continue
dabigatran throughout dermatological surgery, as the possible
risks of stopping the therapy most likely outweigh potential
bleeding complications. When cessation of therapy is abso-
lutely necessary, dabigatran could be stopped 24–48 h before
the procedure and resumed right after an adequate haemosta-
sis was achieved.
Factor Xa inhibitors (fondaparinux, danaparoid,
rivaroxaban, apixaban)
Fondaparinux binds selectively to antithrombin and potentiates
its neutralizing effect on Factor Xa. This results in interruption
© 2014 British Association of Dermatologists
of the blood coagulation cascade and inhibition of both
thrombin formation and thrombus development. Fondapari-
nux is licensed for both acute treatment and short-term pro-
phylaxis of DVT and acute pulmonary embolism and is
usually used in hospital until adequate oral anticoagulation is
established. There are no particular recommendations about
the management of fondaparinux for skin surgery. However,
in patients with superficial venous thrombosis the product
information advises that the drug be stopped where possible
24 h prior to surgery or any other invasive procedure.29 In
view of the serious possible complications and the relatively
short duration of treatment with fondaparinux, it could be
recommended that dermatological surgery be postponed on
either discontinuation of the drug or until commencement of
oral anticoagulation.9
Danaparoid is used as prophylaxis for DVT in patients
undergoing general or orthopaedic surgery and is usually used
for 7–10 days. There are no reports of danaparoid interfering
with cutaneous surgery, most likely due to the acute indica-
tions and the tendency to defer minor procedures after general
surgery. Additionally, at therapeutic doses danaparoid sodium
has no or only a minor effect on haemostatic plug formation,
platelet function and platelet aggregability with no significant
effect on bleeding time.30 In view of the lack of data, it could
be recommended that skin surgery procedures be postponed
until danaparoid discontinuation.
Rivaroxaban and apixaban are the most novel oral anticoag-
ulant agents licensed for long-term prevention of stroke and
systemic embolism. They are a good alternative to warfarin,
benefiting from a much shorter half-life and rapid offset and
onset. This allows for therapy interruption for surgery without
the need for bridging anticoagulation with heparin.31 Rivarox-
aban and apixaban could be stopped 24–48 h (depending on
the risk level) before elective surgery and resumed the same
evening or the next morning for minor procedures.31
Recommendations
Data on perioperative management during surgical procedures,
and cutaneous surgery in particular, in patients on rivaroxaban
or apixaban therapy is too scarce to be able to make recom-
mendations. It is therefore advisable that a specialist haematol-
ogist be consulted to assess the risk/benefit ratio of stopping
the treatment vs. possible increased perioperative bleeding.
Antiplatelet drugs
Aspirin
Aspirin in lower doses is used for long-term primary and sec-
ondary prevention of thrombotic cerebrovascular and cardio-
vascular disease. It inhibits platelet activation by irreversibly
binding to cyclooxygenase and blocking the conversion of ara-
chidonic acid to thromboxanes. Its action is thus persistent for
the whole life span of the platelet. In the past, the common
perioperative practice was to stop aspirin 7–14 days prior to a
British Journal of Dermatology (2015) 172, pp597–605
602 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova
surgical procedure in order to minimize the risk of bleeding.
However, there is currently a growing body of evidence that
this practice is not justified. Aspirin is considered critical for
patients with established cardiovascular disease and its discon-
tinuation can cause a platelet rebound phenomenon character-
ized by increased thromboxane production, decreased
fibrinolysis and clinical prothrombotic state with major
adverse cardiovascular events.32 Furthermore, several studies
have shown that reversal of platelet aggregation could be more
rapid than postulated and occur within 3–5 days of stopping
therapy, thus exposing the patient to a higher thrombotic
risk.33–35
Multiple studies have assessed the risk of bleeding complica-
tions in patients on aspirin undergoing cutaneous surgery.
Most of these did not show an increased risk of bleeding com-
plications.12,15,36,37
Dixon et al.15 reported that bleeding was not increased in
334 patients on aspirin who underwent a total of 829 skin
cancer procedures and aspirin was not an independent risk
factor for bleeding during and after skin cancer surgery.15 In a
large meta-analysis of complications due to anticoagulants in
patients following cutaneous surgery, aspirin users (n = 472
patients) were twice as likely to have a moderate-to-severe
complication, but this showed only a trend towards statistical
significance (P = 0
06) with an absolute risk of aspirin-related
bleeding of about 3%.10 Another meta-analysis on the risk of
increased surgical bleeding in 14 981 patients on low-dose
aspirin reported that this risk was increased by 1
5-fold with-
out increase in overall surgical mortality and/or morbidity.38
In relation to dermatological procedures in this study there
was no significant difference in the risk of bleeding between
patients taking aspirin and age-matched controls. A study of
52 patients on aspirin presenting for a minor dermatological
surgery procedure showed no statistical difference in the rate
of complications when compared with controls.36
Discontinuation of oral antiplatelet agents was found to be
an independent predictor of both death and major ischaemic
events.39 A prospective evaluation of 1358 patients admitted
to hospital with acute coronary syndrome showed that recent
withdrawers of oral antiplatelet therapy had a two-fold
increase in rates of death compared with control prior users
and nonusers of aspirin.39
Incidents of life-threatening DVT, thrombotic stroke40 and
clotted prosthetic valves were reported after cessation of aspi-
rin for MMS.19 Although the number of cases is too limited to
allow for a clear-cut conclusion whether the thrombosis was a
result of the stopped antithrombotic medication or a coincid-
ing event, the time relation still suggests a higher risk.
Recommendations
We suggest that aspirin should not be discontinued prior to
dermatological surgery in patients with increased risk of car-
diovascular or cerebrovascular events, as the possible compli-
cations far outweigh the questionable benefit. However,
aspirin can increase wound bleeding perioperatively and may
British Journal of Dermatology (2015) 172, pp597–605
require longer haemostasis;11 hence the surgeon should ask
the patient about the intake of aspirin prior to surgery in
order to undertake the necessary precautions. In patients tak-
ing aspirin for pain relief, discontinuation of the drug should
be considered as it is not associated with life-threatening
adverse effects. The optimal time to stop the therapy is still
considered to be 7–10 days before surgery, but in view of the
recent studies it might change to 4–5 days should more
robust data be gathered.
Thienopyridines (clopidogrel, prasugrel, ticlopidine)
Thienopyridines are a class of antiplatelet agents that include
clopidogrel, ticlopidine and prasugrel. They exert their action
by reducing platelet aggregation through inhibition of adeno-
sine diphosphate (ADP) via irreversible blockade of the ADP
receptor on platelets. This results in prolongation of bleeding
time and delayed clot retraction.41 Clopidogrel reaches maxi-
mum efficacy on platelet inhibition after 3–7 days and reversal
of its action is impossible. Not only is there no antidote, but
the active metabolite of clopidogrel is still released for several
days after discontinuation of the drug and platelet transfusion
is unhelpful.41
Clopidogrel is indicated for the prevention of atherothrom-
botic events in patients with previous cardiovascular or cere-
brovascular incidents and as primary prophylaxis of such
events in patients with atrial fibrillation. Due to the synergistic
effect, clopidogrel is commonly prescribed together with
aspirin.
Few studies have assessed the side-effects of clopidogrel as
monotherapy in relation to dermatological surgery and the
results are contradictory. Although most studies show a ten-
dency towards increased complication rate, all authors recom-
mend that clopidogrel be continued in view of the prevailing
prothrombotic risk when stopped. Kramer et al.42 did not
observe an increased risk of complications in 32 patients on
clopidogrel and 2073 control subjects undergoing surgery
for excision of skin or subcutaneous lesions under local
anaesthesia.
A retrospective case-note review of 220 patients undergoing
MMS while taking clopidogrel-containing anticoagulation
compared the rate of adverse events with controls taking aspi-
rin monotherapy or no anticoagulants.43 The risk for compli-
cations after the procedure for clopidogrel-containing therapy
was 28 times higher compared with no anticoagulation
(P < 0
001) and six times higher compared with aspirin
monotherapy (P = 0
022). Additionally, severe complications
occurred eight times more commonly in patients taking both
clopidogrel and aspirin than in control individuals taking aspi-
rin alone (P = 0
009). There was no significant difference in
the rate of severe complications between patients taking clopi-
dogrel monotherapy and control subjects not taking anticoag-
ulants (P = 0
15).
In a prospective study of 1911 patients on the adverse
effects of anticoagulants/antiplatelet agents in patients with
dermatological procedures, clopidogrel was found to be
© 2014 British Association of Dermatologists
 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova 603
associated with a significantly higher risk of bleeding com-
pared with controls [odds ratio (OR) = 6
5].2
Discontinuation of clopidogrel treatment in the setting of
major surgery is usually considered within 5–7 days prior to
surgery.44,45 However, newer studies suggest that this period
could be individualized and shortened based on platelet func-
tion tests.46 This allows for reduced postoperative bleeding
and blood consumption as well as a shorter waiting time for
surgery.46
It was suggested that, for low-risk patients on clopidogrel
only and in need of discontinuation, the therapy could be
switched to a short-life nonsteroidal anti-inflammatory drug
(NSAID) for 10 days before surgery. The NSAID could be
stopped 24 h prior to surgery, as this time is sufficient for the
platelet function to recover.47 In low-risk patients on combina-
tion therapy with clopidogrel plus aspirin, continuing aspirin
is sufficient and there is no need for an NSAID to be added.47
Prasugrel is a P2Y12 platelet inhibitor indicated for the pre-
vention of atherothrombotic events in adult patients with
acute coronary syndrome or ST-segment elevation myocardial
infarction undergoing primary or delayed percutaneous coro-
nary intervention. The duration of treatment is usually
12 months. Compared with other thienopyridines, prasugrel is
associated with a higher bleeding risk during instrumenta-
tion.48 For patients who require coronary artery bypass sur-
gery, the last dose of prasugrel should be taken 7 days prior
to the procedure.44
Recommendations
We believe that it is better that clopidogrel is continued in
patients undergoing dermatological surgery, regardless of the
data for increased blood loss and other complications associ-
ated with it. The risk of thromboembolic events after discon-
tinuation of the treatment far outweighs the burden of
clopidogrel complications. If absolutely necessary, in low-risk
patients, clopidogrel could be discontinued at the discretion of
the surgeon for 7 days before the procedure with ongoing
aspirin therapy or addition of an NSAID in patients who are
not taking aspirin.
For prasugrel, given the scarce data in general and the lack
of data from dermatological surgery in particular, unless indis-
pensable, dermatological procedures should be postponed
until the end of treatment. If a procedure cannot be deferred,
then consultation with the prescribing physician is highly
recommended.
Dipyridamole
Dipyridamole inhibits platelet aggregation via inhibition of the
uptake of adenosine into erythrocytes, platelets and endothelial
cells. It is used as an adjunct to oral anticoagulation for pro-
phylaxis of thromboembolism associated with prosthetic heart
valves and as a secondary prevention of ischaemic stroke and
TIA either alone or in conjunction with aspirin. Dipyridamole
does not increase the rate of bleeding complications.11
© 2014 British Association of Dermatologists
Recommendations
Dipyridamole treatment should not be interrupted for cutane-
ous surgery procedures.
Multiagent anticoagulation therapy
It has been reported that patients on multiple antithrombotic
agents (two or more) at the time of surgery are more likely
to bleed than those taking one agent.49
The most common combination of antithrombotic agents is
aspirin and clopidogrel, usually as a secondary prophylaxis for
cardiovascular and cerebrovascular events or in patients with
drug-eluting stents within the first year of stent implantation.
Dual therapy is associated with a higher risk of bleeding com-
plications compared with monotherapy with aspirin in
patients undergoing cardiac surgery.41
A combination of warfarin with other anticoagulants does
not appear to be associated with higher bleeding risk com-
pared with warfarin alone.1
The recommendations from other specialties are that, if
clinically indicated, it is reasonable to continue the preopera-
tive combination of antiplatelet agents (aspirin and a thieno-
pyridine derivative).50
Recommendations
The current evidence suggests that aspirin and clopidogrel
should be continued in patients undergoing low-risk sur-
gery.8,47 However, in patients with a stent at low risk for
thromboembolic events, clopidogrel could be stopped 5 days
before the surgery and aspirin continued. This decision should
only be taken together with the prescriber and for major der-
matological surgery such as facial reconstruction with deep
and wide undermining which is associated with an increased
haemorrhagic risk.
Discussion
The management of antithrombotic medications during cuta-
neous surgery varies greatly from centre to centre and is
highly individualized.13,51–53 Nevertheless, in contrast to the
old practice of discontinuing antithrombotics prior to derma-
tological surgery, the current tendency is for a shift towards
therapy maintenance with meticulous haemostasis and close
follow-up. The most noticeable change is with warfarin, given
that about 80% of dermatological surgeons were stopping it
in a survey from 200253 compared with fewer than 30% in a
survey from 2013.52 The current U.S. guidelines from the
American College of Chest Physicians also recommend contin-
uing warfarin or aspirin perioperatively during minor derma-
tological procedures with an optimized local haemostasis.8
Intraoperative bleeding and/or postoperative haematoma is
rarely wound threatening and has never been reported as life-
threatening or fatal. Thromboembolism, on the other hand,
presents a real risk and there are numerous reports that
British Journal of Dermatology (2015) 172, pp597–605
604 Antithrombotic medications in skin surgery, I. Palamaras and K. Semkova
correlate thromboembolic events to cessation of anticoagulants
or platelet inhibitors.53
To balance the risks and benefits of perioperative continua-
tion or discontinuation of antithrombotic medications it
should be taken into consideration that, whereas severe bleed-
ing may be fatal in approximately 3% of cases,18 thromboem-
bolism leading to stroke is fatal in 40% of cases with resulting
severe disability in 30%.18
A detailed consultation prior to surgery is crucial to identify
high-risk patients and to decide on a management plan by
evaluating haemorrhagic risk factors such as the patient’s med-
ical background (pacemaker, stents), anatomical location and
the type of operation and complexity of closure. In a recent
prospective study of 1911 patients who underwent 1369
MMS and 542 standard surgical excisions, complex repair
(OR = 5
80), graft repair (OR = 7
58), flap repair
(OR = 11
93) and partial closure (OR = 43
13) had increased
risk for bleeding vs. intermediate repair (primary layered
closure).2 In another study, MMS with a repair defect of more
than 2 cm conferred a significantly higher risk of haemor-
rhage compared with incisional and punch biopsies and con-
ventional surgical excision.1 In a prospective study by Amici
et al.54 (including 3788 surgical procedures) bleeding occurred
in 103 procedures (3%) and with significantly higher fre-
quency in patients taking anticoagulants/antiplatelets, in males
and in cases of prolonged procedures, skin flaps or full skin
grafts. The administration of anticoagulants was an indepen-
dent risk factor for haemorrhagic complications (OR = 2
25,
95% confidence interval 1
43–4
44).
We believe that meticulous surgical techniques, elaborate
haemostasis, pressure dressings and close postoperative fol-
low-up are crucial to decrease the risk of bleeding complica-
tions55 and should be enough to neutralize the effects of
concomitant anticoagulants. Patients should always be
informed about this risk and the potential implications of
bleeding, during consent.16
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