Surgical Foundations

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Surgical Foundations January 27, 2015
Venous Thromboembolism a review for surgeons
Bill Geerts, MD, FRCPC Thromboembolism
Consultant, Sunnybrook HSC Professor of Medicine,
University of Toronto National Lead, VTE
Prevention, Can. Pat. Safety Institute Executive,
Thrombosis Canada
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Objectives

1. Patrhogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

3
Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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Thrombosis 101
Blood vessel wall
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Venous Thromboembolism (VTE) 1. Deep vein
thrombosis (DVT) 2. Pulmonary embolism (PE)
Risk factors Small DVT ? Big DVT ? PE ? Death
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(No Transcript)
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Deep vein thrombosis (DVT)

• Thrombus in one or more deep veins
• - legs gtgtgt arms
• - portal, mesenteric, splenic, cerebral, renal
• Proximal DVT - Popliteal ? iliac veins
• - Lead to gt90 of PE
• Distal or calf DVT - Distal to popliteal
• - Posterior tibial, peroneal veins
• - Most calf DVT asymptomatic
• - Rarely lead to PE
• Superficial thrombosis - Not DVT dont lead to
  PE

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Risk factor(s)
Calf DVT
80-90
10-20
Resolves spontaneously
PROXIMAL DVT
rare
gt50
Pulmonary embolism
Death
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What Causes the Blood to Clot when it Should (and
Shouldnt)?
Venous stasis
Activation of coagulation
THROMBOSIS
Injury to the blood vessel wall
Virchows Triad
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Risk Factors for VTE
Major surgery
Trauma major, local leg
Cancer (some)
Cancer treatments
Immobilization bedrest, stroke, paralysis
Acute medical illness
Acute infection
Acute or chronic inflammatory diseases
Estrogen, pregnancy, postpartum
Previous VTE
Family history of VTE
Thrombophilia - Factor V Leiden - Prothrombin 20210A - Deficiency of AT, Pr C, Pr S - Antiphospholipid antibody
Increased age
Obesity
Etc
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Risk of DVT in Hospital Patients Varies

• no prophylaxis routine screening for asympt DVT

Spinal Cord Injury
High risk
Major trauma
THR, TKR, HFS
Gen surg
Gyne / Urol
Moderate risk
Neurosurg
Medical
0 10 20 30 40 50 60 70 80
90 100
Geerts Chest 2008133381S
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VTE Risk Factors in General Surgery

• Procedure-related
• Cancer gt benign
• Open gt laparoscopic
• GA gt regional anesthesia
• Duration of procedure

• Patient-related
• Age
• Previous VTE
• Obesity
• Reduced mobility
• Infection

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Whenever a patient develops DVT or PE, ask the
question Why did this happen?
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70 yo woman with breast cancer 3 years ago, on
tamoxifen, family history of VTE who develops
acute DVT after a hernia repair
DVT
Why did this happen?
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VTE is often multifactorial
Predisposing factors
?age
hernia repair
DVT
tamoxifen
Triggering factor
FH, ?coag abnormality
? Genetic factor
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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D-dimer (D-dummer)

• Formed by effect of plasmin on fibrin
• Increased in VTE
• Also increased
• Generally useless may be misleading
• NEVER done on inpatients or patients at high risk
  of having a positive result
• Virtually no role in surgical patients

plasmin Fibrin FDPs (incl D-dimer)

• after surgery
• trauma
• cancer
• acute infection
• inflammatory disease

• liver disease
• uncomplicated pregnancy
• healthy elderly
• etc

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Investigation of Suspected DVT

• Doppler ultrasonography (Duplex scan) very
  accurate for proximal DVT
• Less accurate for pelvic, calf DVT

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Compression Doppler Ultrasound (Doppler or
Duplex Scan)
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Suspected DVT in a Hospitalized Patient
Proximal Doppler ultrasound
Proximal DVT
Negative for prox DVT
Continue DVT prophylaxis
Treat
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Diagnostic Tests for PE

• D-dimer (D-dummer)
• Not for in-patients, postop, trauma, etc
• Ventilation/Perfusion (V/Q) Scan
• Rules out PE if perfusion is normal
• BUT 60 of scans are nondiagnostic
• Consider in young with normal CXR, renal
  failure, severe contrast allergy
• Tests for DVT
• Doppler ultrasound (DUS)

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Diagnostic Test of Choice for most Patients with
Suspected PE

• CT pulmonary angiogram (CTPA) very accurate for
  PE (?too sensitive)
• Requires contrast, a lot of radiation

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Suspected PE
CTPA
Definite PE
No PE
Consider alternate diagnosis
Treat
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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Traditional Anticoagulants

1. INDIRECT inhibitors of coagulation
2. MULTIPLE SITES of action

XII
XI
IX
VII
VIII
X
AT
warfarin
V
AT
LMWH
heparin
II
fibrinogen
fibrin
THROMBUS
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The new/novel oral anticoagulants (NOACs)

• apixaban (Eliquis)
• dabigatran (Pradaxa)
• edoxaban (Savaysa)
• rivaroxaban (Xarelto)

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New Oral Anticoagulants (NOACs)

1. DIRECT inhibitors of coagulation
2. SINGLE SITES of action

XII
XI
IX
Oral Xa inhibitors rivaroxaban (Xarelto) apixaban
(Eliquis) edoxaban (Savaysa)
VII
VIII
X
warfarin
V
LMWH
heparin
Oral IIa inhibitors dabigatran (Pradaxa)
II
fibrinogen
fibrin
THROMBUS
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NOACs Advantages
Property Advantages
Rapid onset of action No need for IV/SC anticoag
Less variability in anticoagulant effect Fixed dose (or limited options)
No routine lab monitoring Convenient for patients, docs
Relatively rapid offset of action Simplifies pre-procedure Mx
Relatively inexpensive Generally affordable
All of the above Potential for greater/longer use ? fewer thromboemboli
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Approved in Canada Today
apixaban dabigatran rivaroxaban
Orthopedic prophylaxis
Stroke prevention in AF
VTE treatment
Other indications No No No




6mo
Med/surg thromboprophylaxis Mechanical heart
valves Cancer, pregnancy
ODB supported
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Laboratory Monitoring of New OAC

• Poor correlation between standard coag tests (PT,
  PTT) and drug level
• Major variability in reagent/analyzer
• Timing of the test is critical

0 24
Assessment of reversal
dabigatran aPTT
rivaroxaban PT / INR
apixaban none
Monitoring of blood level (limited avail)
dabigatran Hemoclot test
rivaroxaban Anti-Xa
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Management of Bleeding on New Oral Anticoagulants

• No specific antidotes for any
• No human reversal of bleeding studies

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Management of Bleeding in Patients Receiving a
New Anticoagulant

• 1. Dont use
• Plasma, vitamin K, cryoprecipitate

2. GET HELP! (or a good lawyer)
3. Develop/use a local hospital policy
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Patient with bleeding on dabigatran

• When was last dose?
• CBC, creatinine
• aPTT

If aPTT gt40 sec, consult TE or Transfusion
Medicine
Mild bleeding
Moderate-severe Bleeding
Life-threatening Bleeding

• Local hemostatic measures
• Hold 1 or more doses of dabigatran

• Manage bleeding (compression, surgery)
• Fluid ? diuresis
• Transfuse RBCs or platelets if needed (follow
  Sunnybrook guidelines)
• Oral charcoal if dose lt2 hrs before

• Contact Transfusion Medicine
• Tranexamic acid (1 G IV followed by 1 G infusion
  over 8 hours)
• Hemodialysis might be helpful
• Consider FEIBA

50-100 IU/kg
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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Treatment of DVT/PE 3 options
LMWH injections once a day
? ? ? ? ? ?
1
warfarin (INR 2.0-3.0)
5-7 days
Low Molecular Weight Heparin injections once a day
2
? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?
? ? ? ? ? ? ? ? ? ? ? ? ?
Direct oral anticoagulant
(rivaroxaban, apixaban, dabigatran)
3
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Treatment of DVT/PE 3 options
LMWH injections once a day
? ? ? ? ? ?
1
warfarin (INR 2.0-3.0)
5-7 days
Low Molecular Weight Heparin injections once a day
2
? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?
? ? ? ? ? ? ? ? ? ? ? ? ?

• pregnancy, most cancer-associated VTE, high
  bleeding risk

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LMWH Initial Treatment of VTE

• Subcutaneous LMWH
• - dalteparin (Fragmin?) 100 U/kg BID or 200
  U/kg QD
• - enoxaparin (Lovenox?) 1 mg/kg BID or 1.5
  mg/kg QD
• - tinzaparin (Innohep?) 175 U/kg QD
• No lab monitoring or dosage adjustment
• - except in patients with moderate renal
  impairment

• Use pre-filled syringes (and round up)
• - e.g. for 74 kg ? use enoxaparin 120 mg not
  111 mg

• Obesity
• - Use actual body weight (no maximum)
• - e.g. for 150 kg ? use enoxaparin 150 mg
  BID

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Injection of LMWH

• Patients do their own injections
• No need for CCAC

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IV Heparin is Occasionally Preferred over LMWH
1. Unstable patient 2. Severe renal
insufficiency 3. Anticipated invasive
procedure(s) requiring interruption of
anticoagulation 4. Peri-thrombolytic therapy
i.e. very uncommon
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Treatment of DVT/PE 3 options
LMWH injections once a day
? ? ? ? ? ?
1
warfarin (INR 2.0-3.0)
5-7 days
Low Molecular Weight Heparin injections once a day
2
? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?
? ? ? ? ? ? ? ? ? ? ? ? ?

• pregnancy, cancer-associated VTE, high bleeding
  risk

Direct oral anticoagulant
(rivaroxaban, apixaban, dabigatran)
3
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Other Acute Management Issues

• In patients with proven acute DVT or PE
• Dont investigate for PE or DVT
• In PE, dont order echocardiogram
• Dont order hypercoagulability testing
• Dont advise stopping the BCP
• Dont look for occult cancer
• Dont scare the hell outta the patient

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Treatment of VTE
Anticoagulation
Recurrent VTE
0
Time
VTE
3 mos
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Treatment of VTE
Anticoagulation

• surgery
• trauma
• pregnancy
• medical illness

Recurrent VTE

• provoked

0
Time
VTE
3 mos
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Duration of Treatment for VTE
duration
Provoked (transient, reversed risk) 3 months

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Individualized Treatment Duration

• unprovoked VTE
• active cancer
• ongoing risk factor
• high risk thrombophilia
• male

Anticoagulation
Recurrent VTE

• provoked

0
Time
VTE
3 mos
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Duration of Treatment for VTE
duration
Provoked (transient, reversed risk) 3 months

Unprovoked indefinite
Continuing risk (unresolved cancer, AT
deficiency, APLA) indefinite

• Periodic reassessment re
• New patient risk factors for bleeding, thrombosis
• New knowledge
• Patient preference

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For most patients like you . . . (i.e. unprovoked
VTE)

• risks of bleeding
• lifestyle impact
• hassles of testing

• risks of recurrence
• security of being protected

? Continue anticoagulation for now . . .
And we will reassess this decision together
periodically
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Post-thrombotic Syndrome
Treatment 1. prevent recurrent DVT 2.
support stockings
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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34 yo woman with phlegmasia after spine
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Day after catheter thrombolysis
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53 yo woman with massive PE after ankle
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Day after presentation with massive PE
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Indications for Catheter-Directed
Thrombectomy/Thrombolysis
I. In DVT, with extensive clot and severe
symptoms (big clot, cant walk) 2. In PE with
hypotension, overt right heart failure
(increased mortality)
Treatment of choice for massive DVT and massive PE
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Single Indication for an IVC Filter
Recent PROXIMAL DVT PLUS an absolute C/I to
full anticoagulation
NOT for - PE without proximal DVT
- Recurrent VTE/failure of Rx -
Primary prophylaxis - Etc
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IVC Filters

1. Only if indicated (recent proximal DVT absolute
   contraindication to therapeutic anticoagulation)
2. Only use retrievable filters
3. Anticoagulate the patient as soon as safe
4. When patient anticoagulated, have the filter
   removed

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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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Vitamin K Routes Doses
IM NEVER SC NEVER PO ROUTE OF CHOICE -
1 INR lt 5 1 - 2 mg INR gt 5
2.5 - 5 mg IV ROUTE OF CHOICE - 2 1
mg for MINOR bleeding 10 mg for MAJOR bleeding
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Warfarin Reversal
FFP NEVER PCC For major bleeding or reversal
need urgent (Octaplex, Beriplex)
Always give vitamin K too
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

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Surgery in Patients Requiring Long-term
Anticoagulants
1. Thrombosis risk versus 2. Bleeding risk

Need to individualize the approach
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Surgery in Patients Requiring Long-term
Anticoagulants
PRE-operative consideration
1. Thrombosis risk versus 2. Bleeding risk

Need to individualize the approach
POST- operative consideration
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For each case, ask 4 questions

• Does anticoagulation need to be reversed at all?
• 2. If so, how long should anticoagulation be
  stopped before the procedure?
• Should bridging with LMWH be done?
• When can anticoagulant be restarted after the
  procedure (and how)?

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Peri-procedure Management of Warfarin 3 Options
Option Stop warfarin Bridge with LMWH
No No
Yes No
Yes Yes
1
2
3
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Peri-procedure Management of Anticoagulation 3
Options
Very Low Bleeding Risk Procedure
1
Low TE Risk
2
High TE Risk
Bridge
3
Procedure
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Anticoagulation in Patients Requiring
Surgery with Very Low Bleeding Risk
1
warfarin
3.0
INR
2.0
No anticoagulant reversal
1.5
1.0
-5 -4 -3 -2 -1 OR
1 2 3 4 5 6
INR
DAYS
67
Patients with Very Low Bleeding Risk ? dont
reverse warfarin
1

• Cataract surgery
• Most dental procedures
• Upper GI endoscopy biopsy
• Colonoscopy without polypectomy
• Removal of most skin lesions
• Thora-, para-, arthro- centesis

68
Anticoagulation in Usual (i.e. low)
TE Risk Patients Requiring Surgery
2
warfarin
warfarin
3.0
? DVT prophylaxis
INR
2.0
1.5
1.0
-5 -4 -3 -2 -1 OR
1 2 3 4 5 6
INR
DAYS
69
Usual (i.e. low) TE Risk Patients ?
interrupt, dont bridge
2

• Atrial fibrillation (most)
• DVT/PE gt3 months ago
• Mechanical aortic valve
• with no additional risks
• Most miscellaneous
• reasons for anticoagulation

70
Higher TE Risk Patients Requiring
Surgery ? Bridge
3
warfarin
warfarin
3.0
full-dose LMWH ? ? ?
LMWH prophylactic dose, intermediate or
full-dose ? ? ? ? ?
INR
2.0
1.5
1.0
-5 -4 -3 -2 -1 OR 1
2 3 4 5 6
INR
DAYS
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Higher Risk TE Patients ? Bridging
Anticoagulation
3

• DVT lt3 months ago
• All mechanical mitral valves
• Mechanical aortic valve with
• additional risk factors
• Special cases e.g. lawyer, AF, Grade IV LV, TIA
  after colonoscopy

72
Pre-Procedure Stopping of NOACs (apixaban,
dabigatran, rivaroxaban)
Renal Function(CrCL, mL/min) Half-life (hours) How far in advance of procedure should NOAC be stopped?
50 10-15 2 days
30 49 15-20 2-3 days
lt30 More than 25 4-5 days (check aPTT or INR first) get help
Use of NOAC contra-indicated
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Post -Procedure Use of DOACs
Ask yourself Is it OK that the patient be fully
anticoagulated 2 hours after 1st dose?
1
Yes Restart DOAC at therapeutic doses
2
No Delay restart of DOAC at therapeutic doses
3
No DVT prophylaxis with LMWH or prophylactic
dose of DOAC
Restart DOAC at therapeutic doses
-5 -4 -3 -2 -1 OR
1 2 3 4 5 6
DAYS
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Objectives

1. Pathogenesis of VTE and risk factors
2. Investigation of suspected DVT, PE
3. The new oral anticoagulants (NOACs)
4. Management of VTE
5. Management of massive DVT, PE
6. Warfarin reversal
7. Perioperative management of anticoagulated
   patients
8. Prevention of VTE in surgical patients

75
Rationale for Thromboprophylaxis

• 60 of all VTE in the population is
  hospital-acquired
• Most hospital-acquired VTE are preventable
  effectively, safely and inexpensively
• Thromboprophylaxis is standard of care for most
  hospitalized patients

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Who Should Get VTE Prophylaxis?
After most surgery - major general surgery - thoracic surgery - major gynecologic surgery - major urologic surgery - major orthopedic surgery All major trauma
? Most surgical patients in hospital
77
Prevention of VTE in Nonorthopedic Surgical
Patients M. Gould, et al Chest 2012141e227S
Prevention of VTE in Orthopedic Surgery Patients
Y. Falck-Ytter, et al Chest 20081412278S
9th ACCP Guidelines on Antithrombotic Therapy
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Thromboprophylaxis in Surgery (2015)
Patient Group Options Duration
Surgery general, gyne, thoracic, urol LMWH Discharge
Major orthopedics - Hip, knee replacement - Hip fracture rivaroxaban LMWH LMWH 2-6 weeks 2-6 weeks
Major trauma LMWH discharge
High bleeding risk mechanical Until LMWH can start
LMWH low molecular weight heparin (dalteparin,
enoxaparin, tinzaparin)
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VTE and Surgery Dos

• Order prophylaxis for (almost) all patients.
• Use rivaroxaban (or LMWH) as Rx of VTE
• - rivaroxaban 15 mg PO BID x 3 wks ? 20 mg QD
• - dalteparin 200 U/kg SC QD
• - enoxaparin 1 mg/kg SC BID (or 1.5 mg/kg QD)
• 3. Most VTEs can be treated as outpatients
• 4. Use long-term LMWH instead of warfarin or
  NOAC for many cancer patients
• 5. Consider catheter-directed therapy for
  massive DVT/PE

80
VTE and Surgery Donts

1. Get excited about tiny filling defects called
   clots or small PE
2. Order hypercoagulability testing for unexplained
   VTE
3. Order an IVC filter unless recent PROXIMAL DVT
   and anticoagulation not possible
4. Forget to order prophylaxis for (almost) all
   patients

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VTE Summary - 1

• DVT and PE (VTE) are common
• VTE is a multicausal disease
• Risk factors include genetic, acquired,
  situational Was the VTE provoked or unprovoked?
• Investigation of VTE
• DVT Doppler U/S
• PE CTPA

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VTE Summary - 2

• Treatment of VTE
• 1. LMWH ? warfarin
• 2. LMWH alone (cancer, pregnancy)
• 3. DOAC
• Duration of Rx
• Provoked VTE ? 3 months
• Unprovoked VTE ? indefinite (periodic review
  of benefits vs risks)
• Thromboprophylaxis
• LMWH for most