Management of Anticoagulation Therapy in the Peri-operative Period

1
Management of Anticoagulation Therapy in the
Peri-operative Period

• J. Christian Barrett, MD
• Assistant Professor, Division of
  Hematology-Oncology
• Virginia Commonwealth University

2
Management of Anticoagulation Therapy
Peri-operatively

• What are the issues?
• Risk of thrombosis vs. bleeding
• Variable indications for the therapy
• Variable procedural risks
• Reversal of Therapy
• Lack of conclusive evidence

3
Weighing the Risks
THROMBOSIS
HEMORRHAGE

• Venous
• 5-10 fatal
• lt5 disabling
• Arterial
• 20-40 fatal
• 20-50 disabling

• Major bleeding
• 9-13 fatal
• Rarely disabling

4
Case 1

• 70 year old male with a history of atrial
  fibrillation and CHF (EF 30) on chronic warfarin
  therapy with a therapeutic INR of 2.4
• Going for a routine screening colonoscopy
• Asks what he should do with his warfarin for the
  procedure.

5
Thrombotic Risk Non-Valvular Heart Disease

• Non-valvular Atrial Fibrillation
• 4.5 per year risk of arterial thromboembolism
  (range 1-20 based on individual risk factors)
• Warfarin reduces risk by 66
• Left Ventricular Dysfunction
• 18 increase stroke risk for every 5 decrease in
  LV EF
• Warfarin reduces risk by 81
• Aspirin reduces risk by 56

Archives Internal Medicine 19941541449
6
Colonoscopy Risk?

• American Society for Gastrointestinal Endoscopy
  Guidelines
• Low-risk procedures
• EGD, Flex sig, and colonoscopy with/without
  biopsy
• EUS and push enteroscopy
• ERCP and biliary stent placement without
  sphincterotomy
• High-risk procedures
• Gastric (4) or colonoscopic (1-2.5)
  polypectomy
• Laser ablation and coagulation (lt6)
• Endoscopic sphincterotomy (2.5-5)
• EUS-guided biopsy
• Percutaneous gastrostomy
• Stricture dilation

7
ASGE Guideline

• Recommendation for low risk procedure No
  adjustments in anticoagulation need be made
  irrespective of the underlying condition.
• Recommendation for high risk procedure Warfarin
  should be discontinued 3-5 days before the
  scheduled procedure.
• In patients, with high risk conditions, bridging
  with heparin or LMWH may be individualized.
• If to resume after procedure, heparin may resume
  2-6 hours after procedure and warfarin that
  night.
• extra caution if s/p sphincterotomy where major
  hemorrhage risk is 10-15 if reinstituted within
  first 3 days (or if s/p large sessile polyp
  removal where caution in order up to 2 weeks.)

8
Polypectomy Risk

• Retrospective review of 6617 colorectal
  polypectomies in 3138 consecutive patients
• Delayed hemorrhage defined as bloody feces
  reported on gt2 occasions
• 37 patients (1.2) or 38 polypectomies (0.57)
• At second endoscopy, 15 patients had stopped and
  22 patients required endoscopic hemostasis.
• Only 1 patient required blood transfusion
• Anticoagulation use was prohibited for 7 days
  post-procedure per the protocol

Watabe H et al. Gastointest Edosc 20066473-78
9
Polypectomy Risk

• Multivariate analysis
• Polyp-related factors
• Polyp size gt1 cm (OR 4.5 with 95 CI 2.0-10.3)
• Patient-related factors
• Hypertension control (OR 5.6 with 95 CI
  1.8-17.2)
• Associated with a longer interval of recognition
  of bleeding

10
Polypectomy on Anticoagulation

• Retrospective review of 1657 consecutive patients
  with colonoscopic polypectomy
• Immediate hemorrhage defined as bleeding
  sufficient to require endoscopic interventions
  judged by the endoscopist
• 32 patients (1.9)
• 31/32 were classified as MILD (droplt4 g/dL and no
  blood)
• Delayed hemorrhage defined as rectal bleeding
  within 30 days of procedure of sufficient
  severity to require hospitalization for
  management
• 5 patients (0.3)all transfused
• Did not report warfarin use specifically among
  this subgroup

Hui AJ et. Gastrointest Endosc 20045944-48
11
Polypectomy on Anticoagulation

• Among those with bleeding
• No difference seen related to anti-platelet agent
  use
• Warfarin use was significantly associated with
  risk of hemorrhage (plt0.001)
• 4 patients (10.8) among the 37 with hemorrhage
• Median INR 1.41 range 1.09-2.86
• 13 patients (0.8) among the 1620 without
  hemorrhage
• Median INR 1.38 range 1.08-1.84

12
Polypectomy on Anticoagulation

• Retrospective review of 21 patients undergoing 41
  colonoscopic polypectomies
• Held warfarin evening before procedure only
• Median INR 2.0 range 1.4-4.9
• Polypectomy with prophylactic clips if lt1 cm
• No concomitant anti-platelet agent use
• No immediate hemorrhage (all lt10 mL)
• No delayed hemorrhage reported at follow-up (3-8
  weeks)

Friedland and Soetikno. Gastrointest Endosc
20066498-100
13
Cataract Surgery on Anticoagulation

• Reviewed medication use among 19,282 cataract
  surgeries on a RCT
• 4588 patients used aspirin (23.8)
• 13.8 advised to stop use before the procedure
• 22.5 actually did so
• 752 patients used warfarin (3.9)
• 10.5 advised to stop use before the procedure
• 28.3 actually did so

Katz J et al. Ophthalmology 20031101784-1788
14
Cataract Surgery on Anticoagulation

• Among the aspirin users
• No difference seen in ocular hemorrhage events
• 0.56 among those with no routine use
• 0.59 among those who continued aspirin
• Increased incidence of medical events seen
• Myocardial Infarction
• 0.84 among those with no routine use
• 4.16 among those who continued aspirin
• TIA
• 0 among those with no routine use
• 1.19 among those who continued aspirin

15
Cataract Surgery on Anticoagulation

• Among the warfarin users
• No difference seen in ocular hemorrhage events
• 0.55 among those with no routine use
• 0 among those who continued warfarin
• Increased incidence of medical events seen
• Myocardial Infarction
• 1.43 among those with no routine use
• 5.7 among those who continued aspirin

16
Recommendation

• Minor procedure Should be able to proceed
  without any adjustments in anticoagulation
  perioperatively
• If endoscopist unwilling, hold warfarin for 3-4
  days before procedure and resume warfarin same
  day without use of heparin
• If polyp found, second procedure could be
  scheduled off warfarin
• Though some data suggests may be safe to proceed
  at initial procedure if lt1cm, small numbers and
  unconfirmed.

17
Case 2

• 44 year old female with a St Jude (bileaflet)
  mitral valve on warfarin with an INR of 2.9 (goal
  2.5-3.5)
• Is scheduled to have a laparoscopic
  cholecystectomy
• Asks what she should do with her anticoagulation
  therapy for the surgery.

18
Thrombotic Risk Valvular Heart Disease

• 4 per year risk of major arterial
  thromboembolism with a mechanical valve
• plus 1.8 per year risk of valve thrombosis
• 2.2 per year with antiplatelet therapy
• plus 1.6 per year risk of valve thrombosis
• 1 per year with warfarin
• 0.8 per year with an aortic valve
• 1.3 per year with a mitral valve
• plus 0.2 per year risk of valve thrombosis
• majordeath, neurologic deficit or requiring
  surgery

Cannegieter SC et al. Circulation
199489(2)635-41
19
ESC Guidelines

• Recommendation for low risk procedure No
  adjustments in anticoagulation need be made.
• Recommendation for high risk procedure Warfarin
  should be discontinued 3-4 days before the
  scheduled procedure.
• In patients, with high risk factors for
  thrombosis, bridging with heparin is recommended
  stopping 4 hours before the procedure.
• After procedure, heparin may resume within 6-12
  hours after procedure and warfarin as soon as
  possible.
• LMWH is not included in the ESC guidelines

20
High Risk Factors

• Mechanical valve in the mitral position
• High risk prostheses
• Starr Edward, Lillehei Kaster, Omniscience
• Atrial fibrillation
• LVEF lt 30
• Prior thromboembolism
• Hypercoagulable state
• Surgery for malignancy or infection

21
Bridging with Heparin

• Refers to the use of therapeutic doses of UFH or
  LMWH to cover the interval when warfarin dosing
  is subtherapeutic
• LMWH has been demonstrated to be cost-effective
  in cost models compared with UFH
• Data is limited

22
Bridging HeparinPreoperative Planning

• UFH
• Start 36-60 hours after last warfarin dose
• Stop 6 hours before surgery

• LMWH
• Once or twice daily dosing starting 36 hours
  after last warfarin dose
• Stop before surgery
• gt18 hours with twice daily dosing
• gt30 hours with once daily dosing

23
Heparin BridgingPostoperative Planning

• Additional factors to consider
• Post-operative risk of thrombosis (venous not
  arterial risk increased)
• Post-operative bleeding risk

• LMWH
• Start 24 hours after surgery
• If thrombosis risk is high can consider starting
  prophylactic dosing within 12 hours and step up
  the next day

• UFH
• No load and not greater than 18 u/kg/hr starting
  12 hours post-op
• 1st PTT 12hours after start infusion

If the operative bleeding risk is moderate or
high, consider prophylactic dosing instead of
full bridging doses.
24
Recommendation

• High risk of arterial thrombosis with a minor
  surgical bleeding risk
• Stop the warfarin 5 days before the surgery
• Start therapeutic dose LMWH with the AM dose 3
  days before surgery
• Stop LMWH after the AM dose day before surgery
• Resume therapeutic dose LMWH the next day along
  with the warfarin at prior steady state dose
• Stop LMWH once INR gt2 on 2 consecutive days

25
Case 3

• 59 year-old female with a history of
• DVT following her 2nd pregnancy at age 35 treated
• DVT with PTE at age 55 years at which time noted
  to be heterozygous for FVL
• On chronic anticoagulation since the 2nd event
  with an INR 2.6
• Scheduled for a right-sided hemicolectomy
  (non-malignant indication)

26
Thrombotic Risk Venous Thomboembolism

• Risk reduces with longer duration of warfarin
• 50 risk of recurrence within three months
  without anticoagulation
• 40 risk during the first month
• 10 risk during the next two months
• 5 after three months of anticoagulation
• 10-15 per year risk of recurrence among those
  with history of recurrent venous thrombosis
  without continued anticoagulation

27
Venous Thrombosis

• Pre-operatively
• Time from prior venous event
• Time of surgery
• Mobility of the patient
• Post-operatively
• Time from prior venous event
• Operative risk of thrombosis
• Operative risk of hemorrhage

28
Venous Thrombosis

• Pre-operative recommendation
• Stop warfarin 4-5 days before the surgery with no
  bridging or prophylactic dosing of heparin
• Post-operatively recommendation
• Prophylactic dose LMWH and steady state dose of
  warfarin starting 12-24 hours after surgery if
  hemostasis achieved and continued until warfarin
  is therapeutic

29
Case 4

• 38 year-old male discharged 8 days ago following
  a DVT returns off LMWH on warfarin with an INR of
  3.2 with a gun shot wound requiring emergent
  exploratory surgery of the abdomen. Surgeons are
  lining up the OR and asking for recommendations.

30
Warfarin Reversal

• Warfarin Discontinuation
• Vitamin K
• Fresh Frozen Plasma
• Recombinant VIIa

31
Warfarin Discontinuation

• Wide variabilityespecially among elderly
• Generalizations to achieve INR lt1.2 at surgery if
  steady state
• INR 2-3 hold 4 doses preoperatively
• INR 3-4 hold 5 doses preoperatively

White RH et al. Annals of Internal Medicine
199512240-42
32
Vitamin K

• Subcutaneous administration inferior to oral or
  IV which appear equivalent
• IV associated with a risk of hypotension and/or
  anaphylaxis
• Effects seen starting 12-24 hours after
  administration

33
Fresh Frozen Plasma

• Can be infused rapidly if patient can tolerate
  volume
• Cheaper and more widely/rapidly available at many
  centers than rVIIa
• Calculate dose to achieve prothrombin complex
  level of 40 normal plasma
• If subtherapeutic INR, 10mL/kg (3 units in 70 kg
  pt)
• If therapeutic INR, 25mL/kg (7 units in 70 kg pt)
• If supratherapeutic INR, 35mL/kg (10 units in 70
  kg pt)

34
Recombinant Factor VIIa

• Warfarin reversalnot approved indication
• Candidates for consideration
• Life-threatening bleed with INR gt 2.0 ( INR gt1.5
  though Vit K / FFP preferable)
• Emergent surgery unable to be delayed 24 hours
• Other factors to consider
• Fibrinogen gt 120 mg/dL
• MI/angina/stroke ongoing or within prior 4 weeks
• Active DVT or other thrombotic disorder
• Optimal dose is uncertain

35
Recommendations

• Because of the emergent nature of surgery
• Hold warfarin
• Give dose of vitamin K (5-10mg orally or slow IV)
• Fresh frozen plasma 25-35 mL/kg
• or
• Recombinant factor VIIa 10-20 mcg/kg (rounded
  to nearest full vial dose)
• IVC filter placed intraoperatively