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Surgical Foundations January 27, 2015
Bill Geerts, MD, FRCPCThromboembolism Consultant, Sunnybrook HSC
Professor of Medicine, University of TorontoNational Lead, VTE Prevention, Can. Pat. Safety Institute
Executive, Thrombosis Canada
Venous Thromboembolism:
a review for surgeons
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Objectives1. 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
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Objectives1. 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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Fibrin PlateletsRBCs
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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Deep vein thrombosis (DVT)
Thrombus in one or more deep veins - legs >>> arms- portal, mesenteric, splenic, cerebral, renal
Proximal DVT - Popliteal iliac veins - Lead to >90% 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; don’t lead to PE
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Risk factor(s)
PROXIMAL DVT
Calf DVT
Resolvesspontaneously
80-90% 10-20%
Pulmonary embolism
Death
>50%rare
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What Causes the Blood to Clot when it Should (and
Shouldn’t)?
Venousstasis
Activation of coagulation
Injury to the blood vessel
wall
THROMBOSIS
Virchow’s 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
0 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Medical
Gyne / Urol
THR, TKR, HFS
Gen surg
Major trauma
Neurosurg
Spinal Cord Injury
Moderate risk
High risk
no prophylaxis + routine screening for asympt DVT
Geerts – Chest 2008;133:381S
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Procedure-related: Cancer > benign Open > laparoscopic GA > regional anesthesia Duration of procedure
VTE Risk Factors in General Surgery
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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DVT
70 yo woman with breast cancer 3 years ago, on tamoxifen, family history of VTE who develops acute DVT after a hernia repair
Why did this happen?
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+ FH, ?coag abnormality
tamoxifen
hernia repair
age
Triggering factor
Predisposing factors
? Genetic factor
DVT
VTE is often multifactorial
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Objectives1. 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
plasminFibrin 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 DVTDoppler 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 DVT Negative for prox DVT
Treat
Proximal Dopplerultrasound
Continue DVT prophylaxis
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Diagnostic Tests for PED-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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CTPA
Definite PENo PE
TreatConsider alternate diagnosis
Suspected PE
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Objectives1. 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
XII
XI
IX
VIII VII
VLMWHwarfarin
X
heparin
1. INDIRECT inhibitors of coagulation
2. MULTIPLE SITES of action
THROMBUS
fibrinogen fibrin
II
AT
AT
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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)
XII
XI
IX
VIII VII
VLMWHwarfarin
X
Oral Xa inhibitorsrivaroxaban (Xarelto)apixaban (Eliquis)edoxaban (Savaysa)
Oral IIa inhibitorsdabigatran (Pradaxa)
heparin
1. DIRECT inhibitors of coagulation
2. SINGLE SITES of action
fibrinogen fibrin
II
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
#
# #
Med/surg thromboprophylaxisMechanical heart valves
Cancer, pregnancy # ODB supported
6mo
#
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Laboratory Monitoring of New OAC
Assessment of “reversal”dabigatran aPTT
rivaroxaban PT / INR
apixaban none
Monitoring of blood level (limited avail)
dabigatran Hemoclot test
rivaroxaban Anti-Xa
Poor correlation between standard coag tests (PT, PTT) and drug level
Major variability in reagent/analyzer Timing of the test is critical
0 24
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Management of Bleeding on New Oral Anticoagulants
1. No specific antidotes for any
2. No human reversal of bleeding studies
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Management of Bleeding in Patients Receiving a New
Anticoagulant1. Don’t use: Plasma, vitamin K, cryoprecipitate
2. GET HELP! (or a good lawyer)
3. Develop/use a local hospital policy
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Local hemostatic measures
Hold 1 or more doses of dabigatran
Mild bleedingModerate-severe
Bleeding*
Life-threateningBleeding*
Manage bleeding (compression, surgery)
Fluid diuresis Transfuse RBCs or
platelets if needed (follow Sunnybrook guidelines)
Oral charcoal if dose <2 hrs before
If aPTT >40 sec, consult TE or Transfusion Medicine
When was last dose?CBC, creatinine aPTT
Patient with bleeding on dabigatran
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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Objectives1. 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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↓ ↓ ↓ ↓ ↓ ↓
warfarin (INR 2.0-3.0)
5-7 days
↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓
Direct oral anticoagulant (rivaroxaban, apixaban, dabigatran)
LMWH injectionsonce a day
Low Molecular Weight Heparin injections once a day
Treatment of DVT/PE: 3 options
1
2
3
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↓ ↓ ↓ ↓ ↓ ↓
warfarin (INR 2.0-3.0)
5-7 days
↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓
LMWH injectionsonce a day
Low Molecular Weight Heparin injections once a day
Treatment of DVT/PE: 3 options
1
2 pregnancy, most cancer-associated VTE, high
bleeding risk
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LMWH Initial Treatment of VTE
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
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
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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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↓ ↓ ↓ ↓ ↓ ↓
warfarin (INR 2.0-3.0)
5-7 days
↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓
Direct oral anticoagulant (rivaroxaban, apixaban, dabigatran)
LMWH injectionsonce a day
Low Molecular Weight Heparin injections once a day
Treatment of DVT/PE: 3 options
1
2
3
pregnancy, cancer-associated VTE, high bleeding risk
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In patients with proven acute DVT or PE:
Don’t investigate for PE or DVT
In PE, don’t order echocardiogram
Don’t order hypercoagulability testing
Don’t advise stopping the BCP
Don’t look for occult cancer
Don’t scare the hell outta the patient
Other Acute Management Issues
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RecurrentVTE
Anticoagulation
Time
Treatment of VTE
0VTE 3 mos
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RecurrentVTE
Anticoagulation
Time
Treatment of VTE
0
provoked
VTE
surgery trauma pregnancy medical illness
3 mos
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Duration of Treatment for VTE
Provoked (transient, reversed risk) 3 months
duration
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RecurrentVTE
Anticoagulation
Time0
provoked
unprovoked VTE active cancer ongoing risk factor high risk thrombophilia male
VTE
Individualized Treatment Duration
3 mos
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Duration of Treatment for VTE
Provoked (transient, reversed risk) 3 months
*Periodic reassessment re:
1) New patient risk factors for bleeding, thrombosis
2) New knowledge
3) Patient preference
Unprovoked indefinite*
Continuing risk (unresolved cancer, AT deficiency, APLA) indefinite*
duration
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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
And we will reassess this decision together periodically
Continue anticoagulation for now . . .
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Post-thrombotic Syndrome
Treatment: 1. prevent recurrent DVT 2. support stockings
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Objectives1. 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/ThrombolysisI. In DVT, with extensive clot and severe symptoms (“big clot, can’t
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
NOT for: - PE without proximal DVT
- “Recurrent” VTE/failure of Rx
- Primary prophylaxis
- Etc
Recent PROXIMAL DVT PLUS an
absolute C/I to full anticoagulation
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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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Objectives1. 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 < 5 1 - 2 mg
INR > 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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Objectives1. 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 individualizethe approach
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Surgery in Patients Requiring Long-term Anticoagulants
1. Thrombosis risk
versus
2. Bleeding risk
Need to individualizethe approach
PRE-operative consideration
POST- operative consideration
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For each case, ask 4 questions
1. Does anticoagulation need to be reversed at all?
2. If so, how long should anticoagulation be stopped before the procedure?
3. Should bridging with LMWH be done?
4. 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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Very Low Bleeding Risk Procedure
High TE Risk
Low TE Risk
Bridge
Procedure
Peri-procedure Management of Anticoagulation: 3 Options
1
2
3
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Anticoagulation in Patients Requiring
Surgery with Very Low Bleeding Risk3.0
2.0
1.0
INR
-5 -4 -3 -2 -1 OR 1 2 3 4 5 6
warfarin
DAYS
1.5
1
No anticoagulant
reversal
INR
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Patients with Very Low Bleeding Risk don’t reverse warfarin
Cataract surgery
Most dental procedures
Upper GI endoscopy + biopsy
Colonoscopy without polypectomy
Removal of most skin lesions
Thora-, para-, arthro- centesis
1
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3.0
2.0
1.0
INR
-5 -4 -3 -2 -1 OR 1 2 3 4 5 6
warfarin warfarin
DAYS
? DVT prophylaxis
1.5
INR
Anticoagulation in Usual (i.e. low)
TE Risk Patients Requiring Surgery
2
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“Usual” (i.e. low) TE Risk Patients interrupt, don’t
bridge Atrial fibrillation (most)
DVT/PE >3 months ago
Mechanical aortic valve with no additional risks
Most “miscellaneous” reasons for anticoagulation
2
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Higher TE Risk Patients Requiring
Surgery “Bridge”3.0
2.0
1.0
INR
-5 -4 -3 -2 -1 OR 1 2 3 4 5 6
warfarin warfarin
DAYS
LMWH: prophylactic dose, intermediate
or full-dose
full-dose LMWH
1.5
INR
3
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“Higher” Risk TE Patients →Bridging Anticoagulation
DVT <3 months ago
All mechanical mitral valves
Mechanical aortic valve with
additional risk factorsSpecial cases: e.g. lawyer, AF,
Grade IV LV, TIA after colonoscopy
3
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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
<30 * More than 25
4-5 days (check aPTT or INR first)
+ get help
Pre-Procedure Stopping of NOACs (apixaban, dabigatran,
rivaroxaban)
* Use of NOAC contra-indicated
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-5 -4 -3 -2 -1 OR 1 2 3 4 5 6
DAYS
“No”: DVT prophylaxis with LMWH
or prophylactic
dose of DOAC
Post -Procedure Use of DOACs
Restart DOAC at therapeutic doses
“Yes”: Restart DOAC at therapeutic doses
Ask yourself: “Is it OK that the patient be fully anticoagulated 2 hours
after 1st dose?”
1
3
“No” Delay restart of DOAC at therapeutic
doses
2
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Objectives1. 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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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
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Prevention of VTE in Nonorthopedic Surgical Patients
M. Gould, et al
Chest – 2012;141:e227S
9th ACCP Guidelines on Antithromboti
c Therapy
Prevention of VTE in Orthopedic Surgery Patients
Y. Falck-Ytter, et al
Chest – 2008;141:2278S
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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)
Thromboprophylaxis in Surgery (2015)
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VTE and Surgery: Do’s
1. Order prophylaxis for (almost) all patients.
2. 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
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VTE and Surgery: Don’ts
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/SPE: CTPA
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VTE: Summary - 2 Treatment of VTE:
1. LMWH warfarin2. LMWH alone (cancer, pregnancy)3. DOAC
Duration of Rx: Provoked VTE 3 monthsUnprovoked VTE indefinite (periodic review of benefits vs risks)
Thromboprophylaxis:LMWH for most