ADD-ONS / MEDICATION

Perioperative and Periprocedural Management of Antiplatelet Therapy

Created 12/02/2022, last revision 10/08/2023

→ lumbar puncture and antithrombotic therapy is discussed here

long-term antiplatelet therapy may be interrupted for various reasons
- most usually for planned diagnostic or surgical procedures
- in the event of significant bleeding
the decision regarding perioperative/periprocedural antiplatelet therapy depends on the balance between thrombotic (indication) and bleeding risks (type of antiplatelet therapy)
these questions need to be answered:
- is the risk of thrombosis high?
- is it necessary to discontinue antiplatelet therapy?
- is bridging therapy necessary?
- when should the antiplatelet therapy be resumed after the procedure?

Thrombotic risk assessment

very high risk of thrombosis is associated with conditions requiring temporary DAPT
- drug-eluting coronary stent (DES) < 6-12 months
- carotid artery stent < 3 months
- recent stroke (< 3 months)
discontinuation of DAPT results in an increased risk of thrombosis
- the highest risk of thrombosis (up to 20%) is present within 6 weeks following coronary stenting when DAPT is discontinued
- according to the PARIS registry, temporary DAPT interruption for up to 14 days was not associated with an increased rate of thrombotic events, unlike interruption due to non-compliance
it is recommended to postpone elective surgery for a minimum of 4-6 weeks and ideally up to 3 months after stent implantation, with the perioperative continuation of aspirin (whenever possible)
- the risk of stent thrombosis decreases after this period and appears to plateau at 6 months after DES implantation
in stroke patients, the perioperative continuation of aspirin is recommended (whenever possible)

Is it necessary to stop antiplatelet therapy?

The risk of bleeding is unlikely to be increased	simple dental procedures
The risk of bleeding is probably not increased	cataract surgery dermatological procedures TRUS (ultrasound-guided prostate biopsy) spinal and epidural punctures carpal tunnel surgery
The risk of bleeding is apparently not increased	EMG transbronchial biopsy colonoscopic polypectomy endoscopic gastric biopsy ultrasound-guided biopsies sphincterotomy
The risk of bleeding is possibly increased
The risk of bleeding is probably increased	total endoprosthesis (TEP)

Aspirin monotherapy

should be continued, as it has been found to reduce ischemic risk without significantly increasing the risk of major bleeding
consider withdrawal for 3 days for procedures with a very high risk of bleeding (e.g., neurosurgery)
unless contraindicated, a low dose (100mg/d) should be administered and maintained; even higher doses (e.g., 300mg) do not warrant deferral

P2Y12 inhibitor monotherapy

withdraw the drug 3-7 days before the procedure + switch to aspirin if possible
- ticagrelor: 3-5 days (5 days for high-risk procedures)
- clopidogrel: 5 days (at least 3 days in an emergency)
- prasugrel: 7 days (at least 5 days in an emergency)

DAPT (ASA + P2Y12 inhibitor)

consider postponing the procedure if the patient has a moderate-to-high risk for thrombosis until the risk is low (e.g., recent stent)
- it is important not to stop DAPT in the first 30 days after the index event for which it was prescribed
otherwise, maintain aspirin for all procedures unless contraindicated (e.g., neurosurgery)
in patients with a moderate risk of thrombosis (and except for procedures with a low bleeding risk), discontinue the P2Y12 inhibitor as described above)
the strategy for patients at high risk of thrombosis depends on the bleeding risk associated with the procedure
- if bleeding risk is low, continue with DAPT
- for moderate to severe bleeding risk, evaluate individual patients within a multidisciplinary team (use of bridging?)

Timing of antiplatelet therapy discontinuation

ASA and P2Y12 inhibitor

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GP IIb/IIIa antagonists

the exact risk of bleeding is unknown but is likely to be increased due to their mechanism of action (they block the final common pathway)
no laboratory monitoring test is available
the drug must be discontinued before the procedure:
- tirofiban or eptifibatide: withhold ≥ 4-24h before the procedure (timing differs according to various recommendations)
- abciximab: withhold ≥ 48h before the procedure

Others

cilostazol should be discontinued 42h before the procedure
dipyridamole has a half-life of 10-12h; no specific precautions are needed, and it can be restarted after 6h

Urgent reversal of the antiplatelet therapy

urgent reversal of antiplatelet therapy is not a routine procedure (usually considered for acute bleeding) and should be avoided (risk of thrombosis)
- the literature does not consistently demonstrate that the use of antiplatelet agents before an, e.g., ICH leads to poor clinical outcomes, nor does it consistently demonstrate that reversal leads to improved outcomes
platelet transfusion (2-6 units) may be considered (provides functional, circulating platelets); consult a hematologist
- studies have shown mixed results regarding the benefit; there is no standard dose (more units required for patients on DAPT)
- no effect in patients with spontaneous ICH ( PATCH trial)
desmopressin (ddAVP) OCTOSTIM – 0,3 ug/kg +100 mL NS infuse over 15-30 min
- the effect was proven in general surgery (less bleeding and lower transfusion requirements)
- no clear evidence that it f reduces the risk of ICH growth [Schmidt, 2019]
recombinant factor VIIa (rFVIIa) – reverses the inhibitory effects of aspirin or aspirin plus clopidogrel and could be useful for bleeding complications or when acute surgery is needed during treatment with these antiplatelet drugs (Campbell, 2010)
tranexamic acid (EXACYL)
- TXA may reduce bleeding complications from either antiplatelet monotherapy or DAPT (Fischer, 2020)
- multiple studies demonstrated the impact of TXA administration on platelet function through reduced blood loss, transfusion requirements, and the incidence of surgical revisions
bentracimab – a recombinant IgG1 monoclonal antibody seems safe and effective in promptly reversing the antiplatelet effect of ticagrelor in patients undergoing urgent surgery/procedure or with major bleeding (REVERSE-IT trial)

Is bridging required?

there is limited clinical experience with the use of bridging therapy in patients on antiplatelet therapy
do not use heparin (it may increase platelet reactivity and have the opposite effect to that desired)
use of LMWHs is discouraged – lack of evidence of efficacy and safety
if bridging therapy is necessary (in high-risk conditions such as a recent coronary stent), consider antiplatelet rather than an anticoagulant agent
- the IV antiplatelet agents studied to date are the glycoprotein IIb/IIIa inhibitors (tirofiban and eptifibatide) and the P2Y12 adenosine diphosphate receptor inhibitor cangrelor
- the results are controversial and perioperative use of cangrelor has not been approved yet
- large randomized trials are needed to confirm this strategy
a risk-benefit analysis should be performed by a multidisciplinary team on a case-by-case basis
if it is decided that bridging therapy is indicated, the patient should be started on a glycoprotein IIb/IIIa inhibitor 72 h after withdrawal of the P2Y12 inhibitor
- recommended doses are 0.1μg/kg/min for tirofiban and 2μg/kg/min for eptifibatide
- should be maintained for up to 4-6 h before the procedure (Vivas, 2018)
- a loading dose is not required

Restart of the antiplatelet therapy

the timing of resumption should be determined in conjunction with the surgical/interventional team (adequate hemostasis during the procedure and absence of postprocedural bleeding are essential)
in general, antiplatelet therapy is resumed ≥ 24 hours after the procedure
if the patient is at high risk for thrombosis and was receiving DAPT, consider restarting the P2Y12 inhibitor with a loading dose
- clopidogrel: 300-600 mg
- prasugrel: 60 mg
- ticagrelor: 180 mg