Surgical Foundations January 27, 2015 Bill Geerts, MD, FRCPC Thromboembolism Consultant, Sunnybrook HSC Professor of Medicine, University of Toronto National

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

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

Objectives1. Pathogenesis of VTE and risk factors








Fibrin PlateletsRBCs

Thrombosis 101

Blood vessel wall

Venous Thromboembolism (VTE) = 1. Deep vein thrombosis (DVT)2. Pulmonary embolism (PE)

Risk factors

Small DVT Big DVT PE Death

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

Risk factor(s)

PROXIMAL DVT

Calf DVT

Resolvesspontaneously

80-90% 10-20%

Pulmonary embolism

Death

>50%rare

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

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

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

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

Whenever a patient

develops DVT or PE, ask

the question:

“Why did this

happen?”

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?

+ FH, ?coag abnormality

tamoxifen

hernia repair

age

Triggering factor

Predisposing factors

? Genetic factor

DVT

VTE is often multifactorial









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

Investigation of Suspected DVTDoppler ultrasonography (“Duplex

scan”) = very accurate for proximal DVT Less accurate for pelvic, calf DVT

Compression Doppler Ultrasound

(“Doppler” or “Duplex Scan”)

Suspected DVT in a Hospitalized Patient

Proximal DVT Negative for prox DVT

Treat

Proximal Dopplerultrasound

Continue DVT prophylaxis

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)

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

CTPA

Definite PENo PE

TreatConsider alternate diagnosis

Suspected PE









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

The new/novel oral anticoagulants

(NOACs) apixaban (Eliquis®)

dabigatran (Pradaxa®)

[edoxaban (Savaysa®)]

rivaroxaban (Xarelto®)

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

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

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

#

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

Management of Bleeding on New Oral Anticoagulants

1. No specific antidotes for any

2. No human reversal of bleeding studies

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

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









↓ ↓ ↓ ↓ ↓ ↓

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

↓ ↓ ↓ ↓ ↓ ↓


5-7 days

↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓




1

2 pregnancy, most cancer-associated VTE, high

bleeding risk

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

Injection of LMWH

Patients do their own injections

No need for CCAC

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

↓ ↓ ↓ ↓ ↓ ↓


5-7 days

↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓

Direct oral anticoagulant (rivaroxaban, apixaban, dabigatran)




1

2

3

pregnancy, cancer-associated VTE, high bleeding risk

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

RecurrentVTE

Anticoagulation

Time

Treatment of VTE

0VTE 3 mos

RecurrentVTE

Anticoagulation

Time

Treatment of VTE

0

provoked

VTE

surgery trauma pregnancy medical illness

3 mos

Duration of Treatment for VTE

Provoked (transient, reversed risk) 3 months

duration

RecurrentVTE

Anticoagulation

Time0

provoked

unprovoked VTE active cancer ongoing risk factor high risk thrombophilia male

VTE

Individualized Treatment Duration

3 mos

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

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 . . .

Post-thrombotic Syndrome

Treatment: 1. prevent recurrent DVT 2. support stockings









34 yo woman with phlegmasia after spine #

Day after catheter thrombolysis

53 yo woman with massive PE after ankle #

Day after presentation with massive PE

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

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

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









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

Warfarin Reversal

FFP NEVER

PCC For major bleeding or reversal need urgent (Octaplex®, Beriplex®)

** Always give vitamin K too









Surgery in Patients Requiring Long-term Anticoagulants

1. Thrombosis risk

versus

2. Bleeding risk

Need to individualizethe approach

Surgery in Patients Requiring Long-term Anticoagulants

1. Thrombosis risk

versus

2. Bleeding risk

Need to individualizethe approach

PRE-operative consideration

POST- operative consideration

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)?

Peri-procedure Management of Warfarin: 3 Options

Option Stop warfarin Bridge with LMWH

No No

Yes No

Yes Yes

1

2

3

Very Low Bleeding Risk Procedure

High TE Risk

Low TE Risk

Bridge

Procedure

Peri-procedure Management of Anticoagulation: 3 Options

1

2

3

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

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

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

“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

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

“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

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

-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









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

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

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

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)

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

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

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

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

Documents

Surgical Foundations January 27, 2015 Bill Geerts, MD, FRCPC Thromboembolism Consultant, Sunnybrook HSC Professor of Medicine, University of Toronto National