VTE Part 4

Question 1

see slide 108

Answer 1

k

Question 2

Low Dose ASA & Recurrent VTE

Answer 2

Unprovoked VTE, initial therapeutic anticoagulation completed 6-24 mos
• Randomized, double-blind trials of ASA 100 mg daily vs placebo
NEJM 2012;366:1959-67
Relative Risk Reduction of recurrent VTE vs placebo:
• 33% decrease with ASA
• ~80% decrease with DOAC
• ASA decreases risk of recurrent VTE by 1/3 vs placebo

Question 3

What about ASA (CHEST 2016)?

Answer 3

“In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE (Grade 2C).

– Remark: Because aspirin is expected to be much less effective at preventing recurrent VTE than anticoagulants, we do not consider aspirin a reasonable alternative to anticoagulant therapy in patients who want extended therapy. However, if a patient has decided to stop anticoagulants, prevention of recurrent VTE is one of the benefits of aspirin that needs to be
balanced against aspirin’s risk of bleeding and inconvenience. Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped with anticoagulants were started.

Question 4

Mr. Smith is 60 years old and has been treated for 1
year with a DOAC following his unprovoked bilateral
segmental PE. You are seeing him in clinic today and
inform him:

1. If he stops therapy, he is more likely to have a
   recurrent DVT than a recurrent PE.
2. Given that he has been treated for a full year, he
   should stop therapy as his likelihood of recurrent VTE
   is low.
3. After a year of anticoagulant therapy he should
   discontinue his anticoagulant and take ASA to
   minimize bleeding yet have some protection against
   recurrent VTE.
4. After taking either rivaroxaban 20mg daily OR
   apixaban 5mg BID, he can step down to rivaroxaban
   10mg daily OR apixban 2.5mg BID

Answer 4

would not give aspirin (only1/3 reduction compared to 80% with DOAC)

Question 5

High Risk or Active Clot & Inability to Anticoagulate:

Inferior Vena Cava Filters

Answer 5

• Useful in patients with acute proximal DVT with a
contraindication to therapeutic anticoagulation due to high bleeding risk
• Reduce the risk of fatal PE in the short-term
• Increase the risk of DVT in the long term
• Presence of a permanent IVC filter may require long-term anticoagulation – foreign body in vasculature
• Retrievable Filters – removal rates poor (~20%)
– Remove within 3 months or may be permanent
only in ppt with active DVT

Question 6

Post-Thrombotic Syndrome

Answer 6

• Occurs in nearly one-third of patients within
5 years after idiopathic DVT1

• PTS is characterized by:
– Pain
– Edema
– Hyperpigmentation
– Eczema
– Varicose collateral veins
– Venous ulceration
• Severe PTS can lead to intractable, painful venous leg ulcers requiring on-going nursing and medical care

leg swelling, discolouration

Question 7

Post-Thrombotic Syndrome vs.
DVT recurrence / extension

compare pain, swelling appearance

Answer 7

Pain ‘not as bad as when I had the clot’, ‘worse
after I’ve been on my feet’, ‘dull ache’
DVT: ‘just like the first time’,
‘worst it has ever been’

Swelling Usually will decrease after feet are
elevated (above level of the heart), gets
worse as leg is used / day evolves
DVT: Present at all times

Appearance Chronic changes
DVT: taut, Red, Warm

elevate them above heart

Question 8

Post-Thrombotic Syndrome vs.
DVT recurrence / extension

leg symtpos
signs

Answer 8

Leg symptoms
– Heaviness
– Pain
– Swelling
– Itching
– Cramps
– Paresthesia
– Burning pain
• Aggravated by standing or
walking

Signs
– Edema
– Telangiectasia
– Varicose veins
– Venous dilation
– Hyperpigmentation
– Eczema
– Redness
– Dependant cyanosis
– Open/healed ulcers

Question 9

Compression Stockings

Answer 9

• Designed to fit tight on affected
leg, to assist in moving blood from
the leg veins to circulation
• Worn during waking hours
• Avoid if: arterial insufficiency,
intermittent claudication,
uncontrolled heart failure,
infection in area covered by
stocking
• Efficacy: Routine use found not to
reduce PTS or have any important
benefits*
• Use: To reduce acute symptoms of
DVT or chronic symptoms in those
who have developed PTS
• May start wearing within 1 month

Question 10

Chronic Thromboembolic Pulmonary
Hypertension
(CTEPH)

Answer 10

• Serious complication of PE
• Up to 5% of patients with PE are reported to develop CTEPH1
• Thromboemboli may fail to resolve and organize into fibrotic deposits, permanently occluding pulmonary arteries → ↑flow patent vessels → augments shear stress → progressive pulmonary disease
• Initial phase of disease often asymptomatic and followed by progressive dyspnea and hypoxemia2
• Right heart failure can frequently occur
• Progressive condition associated with mortality rates of 4–20%2

need surgical tx

Question 11

Venous Thromboembolism
Prevention is Key

Treatment –
Existing Clot
• DVT or PE
• PE can be lethal, DVT can
lead to PE
• Must treat with quick acting anticoagulant at full therapeutic dosing
• (Most effective strategy is to prevent VTE)

Answer 11

Prophylaxis –
At risk for Clot
• Risk stratification for patients at risk to develop clot (hospitalized)
• Orthopedic (hip/knee) replacement
• General Surgery
• Provide anticoagulant at prophylactic dose (=lower
than full therapeutic dose)

Question 12

VTE Prophylaxis

when is it not indicated?
contra

see slide 119

Answer 12

• Very high risk with orthopedic (hip/knee) replacements
(40-80% will develop VTE)
• Medical / general surgery – 10-40% will develop VTE
• Consider for every hospitalized patient

not indicated if pt fully mobile, length of stay<72 hrs, minor surgery, <60 yrs old

contra: active bleeding, thrombocytopenia, severe HTN, bleeding disorder

Question 13

drugs for VTE prophylaxis

Answer 13

slide 120

Question 14

Which statement is correct?

1. The signs and symptoms of PTS is very similar to
   that of an acute DVT.
2. Post-thrombotic syndrome occurs more
   commonly with larger DVTs that destroy venous
   valves thereby promoting poor blood return.
3. Recurrent or large PEs in the pulmonary arteries
   can lead to left ventricular dysfunction.
4. IVC filters should be inserted in patients with
   evidence of PE that cannot be anticoagulated.

Answer 14

IVC filters should be inserted in patients with

evidence of PE that cannot be anticoagulated.?

Question 15

COVID-19 & VTE

Answer 15

• General trend – saw higher VTE rates in hospitalized
patients earlier in the pandemic compared to later in the
pandemic
• Risk: ICU > non-ICU inpatient > ambulatory
– Hospitalized for COVID, prevalence of VTE 25% (95%CI 19-31%)
+/- thromboprophylaxis (double the rate reported in
hospitalized patients)
– ICU setting higher (17-31%) vs hospital ward (7-31%)
• Evidence evolving rapidly

Question 16

Antithrombotic Therapy:
Balancing Risk

risk of thrombosis, bleeding

Answer 16

Risk of Thrombosis
• Clot event is indicationspecific
– Consequence is indication specific (eg., stroke, PE)
• May have good riskstratification tools (often we
don’t)

Risk Bleeding (Major vs Minor)
• Is not indication specific but may
be specific to a population
• Concern with major bleeding (decline in Hgb 20g/L)
– Intracranial hemorrhage (ICH)
– Non-intracranial bleeding
– Usually treatable (unless ICH)

• Should do a “Clot vs Bleed assessment” on all patients
– Clot risk almost always trumps bleed risk
– For those deemed long-term candidates for anticoagulant therapy, annual reassessment should occur (clot vs bleed risk, appropriateness of agent, renal function, INR control if on warfarin, etc…)

consequences of bleed usually worse

Question 17

Foundational Patient Counseling
warfarin
DOAC

Answer 17

Warfarin:
– Benefit (indication), why they have to take
– Risk (bleeding, CBC)
– Need/rationale for routinecoagulation monitoring (INR)
– Factors affecting INR:
• Acute/ Chronic Diseases
• Drugs/Non-Rx, herbals
• Lifestyle factors (Vitamin K, ETOH, activity level)
– Miscellaneous:
• ID on Warfarin (bracelet, other)
• Procedures – Warfarin is delayed

DOAC
– Benefit (indication)
– Risk (bleeding, CBC)
– No routine coagulation monitoring, CrCl
– Factors:
• Drugs/Non-Rx, herbals
• Drug-Specific:
– Riva 15 & 20 mg – food
– Dabigatran – administration; “dyspepsia”10%
– Miscellaneous:
• ID on OAC (bracelet, other, emergency and cant speak)
• Procedures – OAC needs to be with-held
• Adherence, miss a day, not protected

Question 18

Anticoagulants:
Areas you will see in practice

Anatomy of Heart Valves

which valve higher for thrombosis risk

Answer 18

• Mechanical heart valves
• Need for interruption of chronic therapy for
surgery / procedures

• Semilunar Valves:
– Aortic & Pulmonic
– 3 half-moons (aortic valve semilunar)

• Atrioventricular Valves
– Mitral & Tricuspid
– Structurally different:
• Cusps (leaflets)
• Chordae tendineae
• Papillary muscles

operative risk high for mitral valve > aortic
mitral valve structure and pressure higher risk of thrombosis > aortic

Question 19

Common Diagnoses for Valve

Replacement

Answer 19

• Stenosis – mechanical obstruction to blood flow, net
result of reduced valve orifice area
– Mitral, Aortic

• Regurgitation – backward flow of blood, ‘leaky’ valve,
may be called “insufficiency”
– Mitral, Aortic

• Prolapse – to fall or slip down
– Mitral

– Focus on Mitral & Aortic Valves

Question 20

Types of Valves

2 types

Answer 20

Bioprosthetic (Tissue):
• Heterograph (porcine)
• Up to 30% failure rate at 10-15 years (may expose to anotehr open heart surgery)
• Less thrombogenic
Prosthetic (Mechanical):
• 3 generations: Ball cage, single leaflet, double leaflet
• More durable
• More thrombogenic

Question 21

Heart Valve Replacements

• Risks for thrombosis developing:

Answer 21

Presence of foreign body unable to combat clotting (not living tissue capable of releasing tPA, etc.)

Shear force of blood flow across the valve

Stasis of blood in the atria / ventricle (heart failure)

Tissue injury with implantation

• Ultimate risk of valve failure, stroke

Question 22

Risk of
Thromboembolism wshich type of valve replacement

tissue valve has lowest risk
mecahnical higher risk

Answer 22

Mechanical:
Anticoagulant +/- Antiplatelet

Bioprosthetic Valves:
• Highest risk of thrombosis < 3 months post-surgery
• Long-term risk: 0.2-2.6% per year
• Anticoagulant for some, antiplatelet long-term

• Thrombotic risk = potential for valve failure, stroke
• Risk of thrombosis:
– Mitral&raquo_space; Aortic
– Mechanical (prosthetic)&raquo_space; Tissue (bioprosthetic)
– Presence of other factors increases risk (sluggish blood flow around valve): atrial fibrillation, heart failure, etc.

• Predominant role (based on thrombotic risk):
– Mechanical
• Anticoagulant (warfarin) for all mechanical
• Antiplatelet therapy (ASA 50-100 mg/day) often co-administered in North America for mechanical valves
– Tissue
• Antiplatelet alone vs. Warfarin for 3 months followed by Antiplatelet

Question 23

recommended tx for 
bioprosthetic aortic valve
bio mitral valve
mechanical aortic valve
mech mitral valve

Answer 23

ASA 50-100mg/day
Warfarin X 3 months (Target INR = 2.0-3.0), then ASA
Warfarin* (Target INR = 2.0-3.0)
Warfarin (Target INR = 2.5-3.5)

Question 24

Mechanical Heart Valves: DOACs

SEE SLIDE 137

Answer 24

No DOAC use in mechanical heart valves
– PROACT Xa (warfarin vs apixaban in aortic OnX valves) is underway

• Major bleeding (all pericardial) in dabigatran (N=7; 4%) vs warfarin (N=2, 2%)
• Almost all events occurred in Group A (new valve implant) – thrombi arising from sewing rink of valve

Question 25

Chronic Anticoagulant Therapy:
Need for Interruption

warfarin vs DOAC

Answer 25

• Reason: invasive procedure or surgery wherein bleeding will occur if anticoagulated
• Warfarin – delayed onset / offset
– Depending on risk of thrombosis may need to use LMWH (subcutaneously) given the delay with warfarin and hence time with sub-therapeutic anticoagulation
– Interruption with coverage with LMWH is referred to as “bridging”
– Must hold warfarin 5 days prior to procedure, then will take >/= 4 days following procedure to achieve therapeutic anticoagulation

• DOACs – short onset / offset
– No need for bridging with LMWH, simply hold / restart DOAC

Question 26

• Post-procedure management

warfarin vs DOAC

Answer 26

Bleeding risk of procedure / surgery
– Does the patient need to stop anticoagulant therapy?
• Clotting risk of patient
– Warfarin – comfort being off anticoagulant therapy for
~ 10 days vs if clotting risk substantiates a need to
“bridge” with LMWH
– DOAC – timing of stopping

• Post-procedure management
– Hemostasis intact
– Initiation of anticoagulant(s) based on bleeding risk
associated with the procedure
• Quick acting (DOACs, LMWH) vs delayed (warfarin) acting anticoagulants

start and stop DOACs

Question 27

VKA: Thromboembolic Risk Stratification

last inj of LMWH is at least 24 hours before procedure

Answer 27

High, moderate and low risk strata based on indirect evidence outside of perioperative setting
– High risk: > 10% annual risk for thromboembolism – “we suggest bridging anticoagulation
instead of no bridging”
– Moderate risk: 5-10% annual risk for thromboembolism – “the bridging or no-bridging
approach is based on an assessment of individual patient- and surgery-related factors”
– Low risk: < 5% annual risk of thromboembolism – “we suggest no bridging instead of
bridging”

Question 28

Post-Procedural Management

restaring warfarin vs DOAC

Answer 28

• Restart anticoagulant once hemostasis is intact (this is
based on the procedure/surgery performed)
• Warfarin / LMWH:
– Prolonged time to achieve therapeutic INR if restart warfarin at previous maintenance dosing – local data estimates a median of 20.5 (14.3, 31.3) days
– Warfarin dose at 1.5 maintenance dose for 3 days then assess INR (given delay in onset)
– LMWH dosing as per pre-procedure, acknowledging quick onset, to stop once INR target achieved

• DOAC – start once hemostasis intact
• Restarting DOAC or LMWH → therapeutic anticoagulation
– Ensure hemostasis is intact

Question 29

DOACs: Peri-procedural Management

see slide 144

Answer 29

know general principles

Question 30

You are managing Mr. Hijab’s warfarin therapy and he has informed you he needs to have hernia surgery done and the surgeon wants him to have no anticoagulant on board during the procedure. He has good renal function and needs LMWH bridging. Which of the following is correct?

1. He should hold warfarin for 5 days prior to
   the procedure.
2. He should start injecting his LMWH on the
   day that he starts to withhold his warfarin.
3. He should have his last dose of LMWH 48
   hours before his surgery.
4. All of the statements are correct.

Answer 30

1. He should hold warfarin for 5 days prior to

the procedure.