Transcript What to Test

Three Phases of Thrombotic Events of the
Lower Extremity
Phase 2 – Acute DVT Management
Phase 3 – Preventing Post-thrombotic Syndrome & Recurrent Thrombosis
Marlin W. Schul, MD, RVT, FACPh
Medical Director, Owner – Lafayette Regional Vein & Laser Center
Disclosures
Marlin W. Schul, MD, FACPh, RVT
Principal Investigator in the MARINER trial
Principal Investigator in the GARFIELD trial
Objectives
• Highlight important changes in recommendations
• Review Principles of Acute DVT management
• Distal DVT
• Femoral/Popliteal DVT
• Proximal iliofemoral DVT
Vein Facts
• 10x persons suffer from
venous insufficiency vs. PAD
• All age groups may be
affected
• Stasis Ulcers affect 500,000
persons
– 20,000 new stasis ulcers/year
Vein Facts
• VTE occurs in 1/20 persons
over lifetime
• >500,000 are hospitalized for
DVT/PE each year
• Fatal PE represents the 3rd
most common cause of death
among hospitalized patients.
Vein Facts
• DVT and PE are preventable!
– Studies have shown >40% of cases
failed to receive prophylaxis.*
• Patients surviving VTE +/- PE
are plagued with chronic pain
and swelling
*Spyropoulos A. “Emerging Strategies in the Prevention of Venous Thromboembolism in
Hospitalized Medical Patients.” Chest 2005; 128: 958-69.
ACCP Grading of Recommendations
Strength (For or Against)
Quality of Evidence
A
Grade 1: STRONG
(stated as: “We recommend…”)
•clear benefit
•applies to most
•“just do it”
Grade 2: WEAK
(stated as: “We suggest…”)
•not large benefit or
•uncertain benefit
Decision strongly influenced by:
•clinical differences
•patient preference
Randomized Trials
•Precise (narrow CIs) and
•Bias very unlikely and
•Consistent
B
Randomized Trials
•Less precise (wider CIs) or
•Bias likely but not major or
•Inconsistent
C
Randomized Trials
•Major limitations
Observational Studies (only)
•not very strong or exceptional
VTE Treatment
9th Edition
2012
(mostly on-line)
C. Kearon,
E. A. Akl (chapter editor),
A. J. Comerota,
P. Prandoni,
H. Bounameaux,
S. Z. Goldhaber,
M. E. Nelson,
P. S. Wells,
M. K. Gould,
F. Dentali,
M. Crowther,
S. R. Kahn.
Treatment before Diagnosis
Low Clinical Probability
No treatment if results <24hrs
Grade 2C
Intermediate Clinical Probability
No treatment if results <4hrs
Grade 2C
High Clinical Probability
Treat
Grade 2C
Isolated Distal DVT
(guidelines discourage routine calf vein examination)
Symptoms Not Severe AND No RF for Extension*
Surveillance US over anticoagulation
Grade 2C
Severe Symptoms OR Risk Factors for Extension*
Anticoagulation over surveillance US
Grade 2C
(*Suggested: positive D-dimer; extensive thrombosis; close to proximal; no
reversible RF; cancer; previous VTE; inpatients)
Initial Treatment of DVT/PE
LMWH or Fonda over IV UFH
over SC UFH
Grade 2C
Grade 2B
Once-daily over Twice-daily LMWH
Grade 2C
Home over Hospital for DVT
Grade 1B
Home over Hospital for Low Risk* PE Grade 2B
(* PESI score <85, or Simplified PESI of 0)
Duration of Anticoagulant Therapy
Time-limited (3 months) OR Extended (Indefinite)
•Depending on risk of recurrence (off) and bleeding (on) &
•Case-fatality of VTE and major bleeding
Risk of recurrence
•Surgically provoked
•Non-surgical provoked
•Unprovoked
•Cancer
Risk of Bleeding*
• 0 risk factors
• 1 risk factor
• >2 risk factors
(* Age >65; Age >75; previous bleed; cancer; metastatic cancer; renal failure; liver failure;
thrombocytopenia; previous CVA; DM; anemia; antiplatelets; poor VKA control; co-morbidity;
recent surgery; frequent falls; alcohol abuse)
Current ACCP Guidelines
Clot Burden
Drug/Surgical Management
Iliofemoral/CFV


Duration
Mechanicopharmacological catheter based treatment 6 months or longer
to open the obstructed lesion.
Anticoagulation vs. IVC filter
Unprovoked Fem/Pop

Anticoagulation
o Xa inhibitors
o Heparin/Coumadin
6 months
Provoked Fem/Pop

Anticoagulation
o Xa inhibitors
o Heparin/Coumadin
3 months
Calf Vein Thrombosis


Option A – Duplex study in 2 weeks and use aspirin
Option B – Anticoagulation
o Xa inhibitors
o Heparin/Coumadin
If anti-coagulated, patients should be treated as if they
have a Fem/Pop DVT
Superficial Thrombosis involving saphenous veins >10cm in
length

Prophylactic doses of blood thinner
o Xa inhibitors
o Heparin/Coumadin
4-6 weeks with repeat duplex study immediately should
symptoms worsen
Superficial Thrombosis involving branch veins at the surface
of the skin only

Anti-inflammatories. If unable to tolerate antiinflammatories, use prophylactic doses of blood
thinners as shown in cell above.
6 weeks
SITES OF ACTION
Steps in Coagulation
Coagulation Pathway
Drugs
TF/VIIa
Initiation
X
IX
VIIIa
Va
Xa
Propagation
Fibrin formation
Fibrinogen
IXa
II
Rivaroxaban
Apixaban
Edoxaban
Betrixaban
IIa
Dabigatran
Fibrin
(Hankey GJ and Eikelboom JW. Circulation 2011;123:1436-1450)
Anticoagulation Options - Traditional
Traditional Options/Weaknesses
• LMWH/Coumadin
– Requires bridge
– Even when compliant only 65% with
therapeutic INR
– Requires dietary consistency
– Risk of bleeding relatively higher
– MORE COSTLY when compared to newer
agents
WARFARIN VS. NEW AGENTS
Features
Onset
Dosing
Food effect
Drug interactions
INR Monitoring
Half-life
Antidote
Bridge Required
Warfarin
Slow
Variable
Yes
Many
Yes
Long
Yes
Yes
New Agents
Rapid
Fixed
No
Few
No
Short
No
No
Reversal Agent News
Andexanet Alfa, a recomb human
Factor Xa molecule
• 33 healthy subjects (55-73 Yr)
• Anticoag activity reversed by 94%
within 2-5 minutes (p < 0.0001)
• Effect lasts ~ 1-2 hours
• Restoration of thrombin generation
to pre-anticoagulant levels
• No subjects developed Ab to Factor
X or Xa
DVT Management Principles
• Prevent VTE complications
•
•
•
•
Thrombus extension
Pulmonary Embolus
Post-thrombotic syndrome
Death
• Promote adequate venous
return
• Ambulation
• Compression therapy
Difference in VTE and Major Bleeding after 5 years treatment of 100 patients
Increase (+) or Decrease (−) in Deaths (% per year)
+0.2
+0.4
+2.1
−0.2
0.0
+1.7
−0.7
−0.5
+1.2
−1.1
−0.9
+0.6*
DVT Management Considerations
• Anatomic Pattern
– Calf veins/Distal DVT
– Fem/Pop
– Proximal Iliofemoral DVT
• Role of Interventions
–
–
–
–
–
–
Surgery/CDT
IVC Filters
Inpatient vs. Outpatient
Compression therapy
Anticoagulation
Early ambulation vs. bed rest
Acute Distal DVT
33YOWM with STP calf varices and duplex findings of gastroc DVT.
Management?
Inpatient vs. Outpatient
Bed Rest vs. Early Ambulation
Compress vs. No Compress
Anticoagulation vs. Serial Imaging
In-Patient vs. Out-Patient
Home versus in-hospital Management
Home versus in-hospital Management
Bed Rest vs. Early Ambulation
N=45 all with comparable proximal DVT
Compared leg wraps, GCS, and bedrest
without compression.
Outcomes:
• Quicker pain reduction with compression
& walking
• Quicker reduction in swelling with
compression & walking
• Higher incidence of thrombus extension
in bedrest***
• No increase in PE in patients with
ambulation and compression compared
to bedrest***
Role of Compression Therapy
Role of Compression Therapy
• Reduce edema & pain
• Promote antegrade flow
• Prevent PTS
Acute Distal DVT Summary
Establish an Accurate Diagnosis
• Order a complete whole leg duplex
exam to include the calf veins.
• Recognize that 15% of calf vein
DVTs extend proximally
ACCP Guidelines
Acute Fem/Pop DVT
72YOWM with STP calf varices and duplex findings of free
floating POPV DVT.
Management?
Inpatient vs. Outpatient
Bed Rest vs. Early Ambulation
Compress vs. No Compress
Anticoagulation vs. Serial Imaging
IVC Filter?
Surgical or Thrombolysis Rx?
Role of IVC Filters
• Indications
• Patients with acute DVT or PE, where
anticoagulation is contraindicated.
• Type of Filter
• Retrievable filters vs. permanent filters
• Complications of IVC Filters
• Increase risk of recurrent DVT
• Do not alter combined frequency of
DVT/PE
• Acute thrombosis at insertion site ~10%
• Systemic review suggests that PTS
becomes more prevalent
Acute Iliofemoral DVT
25 YOWF with post partum iliofemoral DVT at 1
wk.
ACCP ‘Guidance’?
Open Thrombectomy vs. Catheter Directed Thrombolysis
(CDT)
Indications:
• Iliofemoral DVT
• Symptoms <7 days
• Good functional status
• Life Expectancy > 1 yr
• Resources and expertise are
available
Acute Iliofemoral DVT
25 YOWF with immediate post partum
iliofemoral DVT
Immediate post CDT
Images Compliments of Dr. S. Shafique
Long-term Considerations
Preventing Long-term Complications
Long-term concerns
• Recurrent VTE
• Post-thrombotic Syndrome
Of 528 subjects, 101 developed recurrent VTE. Of first recurrences, 47%
occurred in the previously affected limb. 119 subjects developed post
thrombotic syndrome (PTS). Incidence of PTS was 18% after 1 year and
24.5% after two years follow up.
Recurrent Thrombosis
Treatment Concerns
• Intensity of anticoagulation
– Coumadin vs. LMWH vs. Xa inhibitors
• Duration of Anticoagulation
– Short vs. Extended (Prandoni & Kearon)
• Residual thrombus vs. ongoing
thrombotic activity
– RVO vs. D-Dimer (Cosmi vs. Prandoni)
Individual Risk Factors
• Idiopathic vs. provoked (Prandoni)
• Male > Female (Roach)
• Known thrombophilia (Prandoni)
• Malignancy (Prandoni)
Recurrent Thrombosis
Baseline Risk Factors
•
•
•
•
•
Known inherited thrombophilia
Male gender
Unprovoked DVT > Unprovoked PE
Advanced age
Obesity & Lipid Lowering Drugs
Post-baseline Predictors
• Residual venous obstruction
• D-Dimer
• Post thrombotic syndrome
Current Debate
Cosmi & Meissner
Prandoni & Caprini
Role of D-Dimer & Discontinuing OAT
Transition off of OAT – Role of ASA
Controversy RE: Thrombophilia Testing
When to Test
• Major unprovoked events
• Significant Long term concerns
• Answer will make a difference in
management or long-term health
• Consider underlying malignancy
What to Test
• Common things are common
– May test genetic markers anytime
• FVL
• PT Gene Mutation
– Ease family concerns/low cost
• Full Work Up
– Consider the underlying risks
Reference predictors of PTS
N=241 with 1st DVT
• Intensity of OAT
• Initial Burden of Thrombus
• Use of compression therapy early
in treatment (Cochrane Reviews)
• Known thrombophilia
• Recurrent thrombosis
Healthy Vein Habits Post VTE
• Ambulation immediately
• Compression therapy
• ASA as means to prevent
recurrent VTE by 50%
• Use selectively for subjects without
ongoing major risk factors.
Post-Test
Inpatient management of
Acute DVT remains the
standard of care.
True / False
Post-Test
Ambulation is preferred
over bed rest for patients
with Acute DVT.
True / False
Post-Test
Acute DVT may be
effectively managed with
oral Xa inhibitors, e.g. no
bridging agents.
True / False
Post-Test
Compression therapy is
indicated for all patients
with Acute DVT.
True / False
Post-Test
All compression stockings
are the same.
True / False
Post-Test
IVC Filters are indicated
in patients with Acute
proximal DVT who are not
candidates for
anticoagulation.
True / False
Post-Test
Calf vein thrombi are
typically managed the
same as acute proximal
iliofemoral DVT.
True / False
Thank you!