Bridge Therapy: Peri-operative Anticoagulation

1
Bridge Therapy Peri-operative Anticoagulation
Management Amjad AlMahameed, MD,
MPH Division of Cardiology Beth Israel Deaconess
Medical Center Boston
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RATIONALE FOR BRIDGING
Cross Coverage to Therapeutic INR
Requiring AC but have not achieved Therapeutic
INR
Already Rxed w chronic AC and now documented
drop in INR
Peri-procedural
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BENEFITS Supporting Need for Bridge Therapy

• high daily risk estimate for thrombosis when
  patients remain unprotected for several days
  peri-procedure
• Subtherapeutic INR offers little or no protection
• Possible rebound hypercoaguable state, especially
  when warfarin reinitiated leading to thrombosis
• Bleeding complications can be controlled while
  CVA or PE may have lasting effect
• New drugs and new data offer increased ease of
  therapy

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SAFE SURGERY Choosing the Best Approach
Must Answer three basic questions

• 1- What is the risk of bleeding with AC based
  upon the type of procedure and patients history?
• 2- What is the risk of thrombosis if AC reduced
  or stopped?
• 3- Which is the best bridging strategy (bridging
  medication, timing, outpatient vs. inpatient)

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SAFE SURGERYWhat is the Risk of pei-operative
Thrombosis?
DEFICIENCIES IN CURRENT EVIDENCE

• From descriptive studies and clinical experience
• Does not account for
• - the added risk of thrombosis during surgery
• - the rebound theory
• - the heterogeneity in patients
  characteristics
• - the post-operative clinical course

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SAFE SURGERY What is the Optimal Upper INR
Level?

• Type of Surgery
• Patients Characteristics
• Integrity of the hemostasis/coagulation system
• Technical/intraoperative factor

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Current Standard in Bridge Therapy

Prospective Randomized Controlled Trials
Expert Opinion/Consensus
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Prospective Randomized Trials (Bridge Therapy)
None available, but some in progress and others
in the planning phase
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Expert Opinion on Bridge Therapy

• British Society of Hematology
• American College of Chest Physicians (ACCP)
• Kearon and Hirsh article NEJM, May, 1997
• Pregnancy and Prosthetic Valve Clinical Consensus
  (PPCR)
• Douketis article

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British Society of Haematology
3 2 1.3 1
Therapeutic INR range
INR
Normal INR Range 1-1.3
Procedure
Procedure
Pre-Op Day 3 2
1
UFH when INR lt 2
Stop Warfarin /- Vit K
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American College of Chest Physicians
3 2 1.3 1
Therapeutic INR range
INR
Normal INR Range 1-1.3
Procedure
Procedure
Pre-Op Day 5 4
3 1

Low or full dose UFH or LMWH when INR lt
2
Stop Warfarin /- Vit K
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Kearom and Hirsh RecommendationsNEJM, May, 1997
Indication Before After
VTE 1 month IV UFH IV UFH
Month 2-3 No Heparin IV Heparin
Recurrent No Heparin SC
Heparin Arterial 1 month IV Heparin
IV Heparin Mechanical Valve No Heparin
SC Heparin A Fib No Heparin No Heparin
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Limitations of Kearon and Hirsh Recommendations

• Discounts rebound phenomena
• Estimate 100-fold ? in VTE risk but no ? in ATE
  risk versus Wahls review (5 of 493 patients had
  ATE , 4 died)
• Low estimate ATE risk off warfarin (4.5 / year A
  fib, 8 /year mechanical valve)
• Estimate heparin bleeding risk of 3 per 2 days
• Recommends SC vitamin K, does not utilize LMWH
• Does not focus on patients characteristics (type
  of valve, risk factors for ATE in A Fib)
• SC (or no) heparin in A fib and mechanical
  valves??!!

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Douketis Article Thrombosis Research, 108 (2003)
3-13

• Better risk stratification of
• - risk of post-procedural bleed
• - risk of peri procedure thrombotic
• complications
• Advocates normal or near normal INR at the time
  of surgery (earlier withdrawal of warfarin)
• Includes practical algorithms that guide
  perioperative management of AC

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Bleeding Risk Classification and Postoperative AC
Post-op AC
Type of Procedure
Bleeding Risk
Low-dose LMWH POD 1-2 Warfarin evening POD
1-2 Full dose LMWH POD 2-3 h
NSG, Prostate/bladder, OHS, major vascular,
renal Bx, polypectomy, major CA surgery
High Risk
Low-dose LMWH warfarin evening of OR day Full
dose LMWH POD 1-2
Major abd, thoracic, and orthopedic PPM
insertion
Moderate Risk
Catarct, cutaneous, laparascopic choly/hernia
repai, cardiac cath
Low-dose LMWH warfarin evening of OR day Full
dose LMWH POD 1
Low Risk
J.D. Douketis, Thrombosis Research 108 (2003)
3-13
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Perioperative AC Rx in Patients With Mechanical
Valves
Thromboembolism Risk Category
Patient Characteristics
Suggested Management
Bridging strongly recommended
Stroke or TIA lt 1 mo Any MV Caged-ball or single
leaflet tilting disc AV
High
Star-Edwards Bjork-Shiley Medtronic-Hall Omnicarbo
n
A Fib, CVA, TIA, emboli, LV dysfxn, gt75 y/o, HTN,
DM
Moderate
Bridging should be considered
Bileaflet tilting disc AV and gt 2 stroke RF
St. Jude Carbomedics
Low
Bileaflet tilting disc AV and lt 2 stroke RF
Bridging is optional
J.D. Douketis, Thrombosis Research 108 (2003)
3-13
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Perioperative AC Rx in Patients With Chronic A
Fib
Thromboembolism Risk Category
Patient Characteristics
Suggested Management
Bridging strongly recommended
Stroke or TIA lt 1 mo Any MV Rheumatic MV Disease
High
A Fib, CVA, TIA, emboli, LV dysfxn, gt75 y/o, HTN,
DM
Moderate
Bridging should be considered
Chronic A Fib and gt 2 stroke RF
Low
Chronic A Fib and lt 2 stroke RF
Bridging is optional
J.D. Douketis, Thrombosis Research 108 (2003)
3-13
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Regardless of thromboembolism risk category,
patients characteristics take precedent!

• A Fib
• CVA
• TIA
• arterial emboli
• LV dysfxn
• gt75 y/o
• HTN
• DM

Bridging strongly recommended
J.D. Douketis, Thrombosis Research 108 (2003)
3-13
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Perioperative AC Rx in Patients With VTE
VTE Recurrence Risk
Patient Characteristics
Suggested Management
Bridging strongly recommended
Recent VTE (lt 3 wks) Active CA APL Ab or
LA Major comorbid disease
High
Bridging should be considered
VTE lt 6 months VTE with previous AC
interruption
Moderate
Low
None of the above
Bridging is optional
J.D. Douketis, Thrombosis Research 108 (2003)
3-13
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Emergency Surgery in the Anticoagulated Patient

• D/C all anticoagulants
• If INR gt2.5 plasma or factor concentrate (/-
  Vit k)
• Prepare PRBC, platelet, and FFP
• Consider PRBC transfusion to augment hematocrit
  especially in pts with cardiac disease
• Watch for volume overload, dilutional
  thrombocytopenia and coagulaopathy

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Available Anticoagulants

• UFH Discovered 1916, clinical use 1935
• Vitamin K antagonists discovered 1940, clinical
  use 1960s, clinical trials 1990s
• LMWHs Discovered 1976, clinical trials started
  in 1980s and ongoing
• Parenteral DTIs Lepirudin (recombinant Hirudin)
  and Argatroban approved for Rx of HIT/HIT-T
  (3/1998 and 6/2000). Bivalirudin (modified
  Hirudin), for patients with ACS undergoing PCI

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New Anticoagulants

• Oral Small-Molecule DTIs Ximelagatran. No FDA
  approval
• Pentasaccharide Fondaparinux (anti Xa activity),
  FDA approval for VTE prophylaxis in orthopaedic
  surgery 12/2001. Idraparinux Being evaluated for
  chronic treatment of VTE

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Choosing the Best Bridging Medication

• Depends on patient characteristics
• - Recent bleed
• - Renal function
• - Actual body weight
• - Pre-op INR
• - Baseline coagulation tests
• - History of Heparin-Induced Thrombocytopenia
• Available data, clinical experience, and Douketis
  advocate bridging with LMWH if possible

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BRIDGING STRATEGY
Prophylactic Dose LMWH
Start full Dose LMWH
Resume full dose LMWH
Hold Coumadin
Coumadin
Resume Coumadin
Surgery
Day -7 -5 -3 -1
1 2 3 5
v INR v CBC
v INR
v INR
Days post-op
Days pre-op
J.D. Douketis, Thrombosis Research 108 (2003)
3-13