Transcript newer anti-coagulants

ANTI-COAGULANTS:
Surgical Perspective
• Many patients with underlying cardiovascular
disease require long-term anticoagulation.
• The perioperative or periprocedural
management of patients who require
temporary interruption of anticoagulant or
antiplatelet medications is a common and
often challenging clinical problem.
• Interruption of anticoagulation is associated
with an increased risk of thromboembolic
events such as stroke, mechanical valve
thrombosis, stent thrombosis, and venous
thromboembolism (VTE).
ANTICOAGULANTS
LOW BLEEDING RISK
• The American Society of Gastrointestinal Endoscopy
divided endoscopic procedures into low and high risk
• Low bleeding-risk endoscopic procedures do not
require a change in anticoagulation.
• Upper endoscopy with or without biopsy
• Flexible sigmoidoscopy with or without biopsy
• Colonoscopy with or without biopsy
• Endoscopic retrograde cannulation of the pancreatic
duct without sphincterotomy
• Biliary stent insertion without sphincterotomy
• Endosonography without fine-needle
aspiration
HIGH BLEEDING RISK
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Polypectomy
Laser ablation and coagulation
Endoscopic sphincterotomy
Pneumatic or bougie dilation
Percutaneous endoscopic gastrostomy tube
placement
• Treatment of varices
BRIDGING
• Bridging anticoagulation, though frequently
recommended, can increase the risk of perioperative
bleeding (Arch Intern Med 2008;168:6).
– Resumption of bridging therapy within 24 hours is
probably safe for minor procedures.
– For patients undergoing major surgery, restarting
bridging therapy within 24 hours of surgery is
associated with unacceptably high bleeding rates
(J Thromb Haemost 2007;5:2211 ).
• One option is to delay restarting bridging until 48 to
72 hours postoperatively. A second option is to
resume the VKA postoperatively within 12 to 24
hours as above and forego bridging postoperatively
• Choices for bridging therapy are generally the
LMWHs and UFH. There is less experience with
other agents (e.g., fondaparinux), and their use
cannot be considered routine.
– LMWHs have the advantages of relatively
predictable pharmacokinetics in patients with
normal renal function and ability to be administered
subcutaneously.
• Monitoring of anticoagulant effect is typically not
required.
• The effect of LMWH can linger if a therapeutic anticoagulation
dose is given <1 day prior to surgery (Ann Intern Med
2007;146:184 ). Thus, the last dose should be given 24 hours prior
to surgery.
• UFH can be used in patients with renal disease, but typically it
must be administered IV and requires frequent monitoring of the
aPTT, necessitating hospitalization.
• UFH should be stopped 4 hours prior to the planned surgical
procedure to allow the anticoagulant effect to wane.
• Patients at high risk of thromboembolic events
should typically be treated with bridging
therapy. Full-dose LMWH is recommended over
UFH, though either is acceptable.
• Though the ACCP recommendation is evidence
based, it should be noted that the older ACC/AHA
guidelines on management of valvular disease
continue to recommend IV UFH for bridging in
patients with prosthetic valves (Circulation
2006;114:e84 )
• For patients at moderate risk of
thromboembolic events, treatment with
bridging is recommended, but options other
than full anticoagulation are optional.
Therapeutic anticoagulation with LMWH or
UFH (as for high-risk patients) is preferred, but
treatment with DVT prophylaxis dosing of
LMWH is considered an acceptable
alternative.
• Patients at low risk for thromboembolism are
not felt to require bridging therapy.
• Treatment with DVT prophylaxis doses of
LMWH is an alternative.
• Acute gastro-intestinal haemorrhage in patients on
anticoagulant or antiplatelet agents is a high-risk
situation. The immediate risk to the patient from
haemorrhage may outweigh the risk of thrombosis as a
result of stopping anticoagulant or antiplatelet therapy.
• Patients need to be assessed on an individual basis.
For patients with high-risk conditions on warfarin, then
this can be discontinued with or without substitution
of heparin depending on the severity of haemorrhage
and risk of discontinuing anticoagulant therapy.
• There is a high risk of acute myocardial
infarction or death if clopidogrel is
discontinued in patients with coronary stents,
particularly early after implantation, but
extending up to 1 year after this.
• Endoscopy should be attempted as soon as safely possible
after urgent liaison between the patient’s cardiologist and
the consultant specialist undertaking endoscopy.
• Clopidogrel should not be discontinued without discussion
with a cardiologist. If clopidogrel therapy needs to be
discontinued in this context, then this should be limited to
a maximum of 5 days as the risk of stent thrombosis
increases after this interval.
• Early therapeutic endoscopic intervention may achieve
haemostasis with minimal or no cessation of anticoagulant
or antiplatelet therapy, and should be the first aim.
(Evidence grade IV. Recommendation grade C.)
WARFARIN VS NOA
• Standard bleeding risk procedures(including
colonoscopy, laparoscopic procedures, and
any aspirations not involving the spinal canal)
in patients with normal CrCl (50 mL/min),
dabigatran use should be stopped at least 48
hours before the procedure.
• Rivaroxaban and apixaban use should be
stopped at least 24 hours before the
procedure
• In patients with impaired CrCl (<50 mL/min),
dabigatran therapy should be stopped at least 72
hours before the procedure if CrCl is 30 to less than
50 mL/min and at least 4 days earlier if CrCl is less
than 30 mL/min.
• Rivaroxaban and apixaban administration should be
stopped at least 48 hours before the procedure.
• High bleeding risk procedures( including major
cardiac surgery, insertion of pacemakers or
defibrillators, neurosurgery, major
cancer/urologic/vascular surgery, spinal
puncture, etc.) In patients with normal CrCl
(50 mL/min), dabigatran, rivaroxaban, and
apixaban administration should be stopped at
least 48 hours before procedure.
• In patients with impaired CrCl (<50 mL/min),
dabigatran use should be stopped at least 4 days
before the procedure if CrCl is 30 to less than 50
mL/min
• and at least 6 days earlier if CrCl is less than 30
mL/min . Rivaroxaban and apixaban administration
should be stopped at least 4 days before the
procedure.
REINITIATION
• This process depends on the nature of the surgery,
the urgency for restarting thromboprophylaxis
therapy, and the hemostatic state of the patient.
• Given the rapid clearance of the NOAs from the
circulation and the rapid onset of action when
reintroduced, no bridging therapy with LMWH or
unfractionated heparin is necessary.
• Anticoagulation may be resumed the same evening,
at least 4 to 6 hours after surgery with a reduced
dose (dabigatran, 75 mg; rivaroxaban, 10 mg; or
apixaban, 2.5 mg) for the first dose and, thereafter,
the usual maintenance dose.
• For major abdominal surgery or urologic surgery with
incomplete hemostasis, resumption should be
delayed until there is adequate hemostasis
• There are no standardised tests readily
available in routine practice for monitoring the
anticoagulant effects of the NOACs.
• There are no specific antidotes for NOACs
• Administration of oral activated charcoal
retards absorption of recently ingested drug,
eg, within a couple of hours of intake.( Am J
Hematol. 2012;87)
• Given that only 35% of dabigatran is bound to
plasma proteins, hemodialysis typically
removes 60% of dabigatran and should be
considered, especially in patients with
impaired renal function.
• Octaplex
A randomized controlled study using a
nonactivated 4-factor PCC showed
normalization of the PT alone in patients
taking rivaroxaban but not dabigatran.
• There is some evidence to support the use of
activated prothrombin complex concentrates
(aPCCs) [Feiba®] for reversal of dabigatran or
four-factor PCC [Octaplex®] as reversal agents
for rivaroxaban and apixaban but data is
limited.