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Proximal versus Calf Vein
Thrombosis: Differences in
Management
Marc A. Passman, M.D.
Associate Professor of Surgery
University of Alabama at Birmingham
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Disclosure
Marc Passman, M.D.
I have no financial relationship(s) to disclose.
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Learning Objectives
• Review currently available anticoagulation options and role in VTE treatment.
• Implement current evidence based guideline recommendations for VTE treatment
• Understand difference between proximal and calf DVT and controversies in treatment options.
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Acute VTE Treatment Modalities
• Untreated DVT PE approximately 50% of patients– Death in 20%
• Initial Treatment = ANTICOAGULATION
• Anticoagulation reduces risk of PE to 1-2% in adequately dosed patients
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5
Acute VTETreatment Modalities
The mainstay of therapy
• Full-dose anticoagulation
• Compression
Optional interventions
• Thrombolytic therapy (catheter-directed or
systemic)
• Thrombectomy (percutaneous or surgical)
• Angioplasty and stenting
• Inferior vena cava interruption
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Treatment of VTE
Current Anticoagulants• Glycosaminoglycans (act mostly by
stimulating AT III)
– Unfractionated heparin (UFH)
– Low-molecular–weight heparin (LMWH)
– Fondaparinux (pentasaccharide)
• Synthetic anticoagulants (for patients
with heparin-induced thrombocytopenia)
– Direct (ie, ATIII-independent) antithrombins
(argatroban, lepirudin, bivalirudin)
• Vitamin K antagonists
– Warfarin
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Glycosaminoglycans
UFH LMWH Fondaparinux
Source Porcine/bovine Altered UFH Synthetic
Mean no. of 36 13 5
saccharides
Action ATIII, IIa>Xa ATIII, Xa>IIa ATIII, Xa
Plasma protein binding +++ + +
Bioavailability Variable 90% 100%
Half-life, h Variable (SQ) ~6 (SQ) ~17 (SQ)
<1-3 (IV)
PF4 binding ++ ++ ++
GAG/PF4 antibodies ++ ++ ++
HIT 1%-5% 0.3%-0.8% Almost never
Effect of renal dysfunction ++ ++ ++
Monitoring PTT Anti-Xa Anti-Xa
Protamine as antidote ++ + –
Pregnancy category C B B
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Warfarin
Advantages:
Oral
Effective
Antidotes exist(vitamin K, fresh frozen plasma, “4-factor” concentrates)
Long half-life
• Disadvantages:
Long half-life
Not immediately active
Very low therapeutic index
Very significant drug / dietary interactions
Very significant effect of hepatobiliary and gastrointestinal function
Requires close monitoring
Protein C / S deficiency - paradoxically hypercoagulable
Vitamin K IV, FFP, and “4-factor” concentrates have risks
Pregnancy category X (“warfarin embryopathy,” midface hypoplasia and skeletal defects, especially weeks 6-9); fetal hemorrhaging (3rd trimester)
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Direct Thrombin Inhibitors
Argatroban Lepirudin Bivalirudin
Standard loading dose None 0.2 mg/kga 0.75 mg/kg
Standard infusion dose 2 µg/kg/min 0.1 mg/kg/h 1.75 mg/kg/h
How monitored PTTb PTT PTT
Target PTT range 1.5-3.0 x 1.5-2.5 x 1.5-2.5 x
Antidote None None None
Pregnancy category B B B
Half-life 45 min 75 min 25 min
Effect of renal dysfunction – ++++a ++a
Effect of liver dysfunction ++a – –
Antibodies No Occasionalb Rare
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The New Anticoagulants
New Anticoagulants
Rivaroxaban: oral anti-Xa
Apixaban: oral anti-Xa
Dabigatran: oral antithrombin
Principal areas of study
VTE prophylaxis
Treatment of acute VTE and extended prophylaxis
Stroke prevention in chronic atrial fibrillation
Acute coronary syndrome
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DabigatranFDA Approval
FDA NEWS RELEASE
• For Immediate Release: Oct. 19, 2010
Consumer Inquiries: 888-INFO-FDA
FDA approves Pradaxa to prevent stroke in
people with atrial fibrillation
– The U.S. Food and Drug Administration today
approved Pradaxa capsules (dabigatran etexilate)
for the prevention of stroke and blood clots in
patients with abnormal heart rhythm (atrial
fibrillation).
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Acute DVT/PE: Initial
Anticoagulant Therapy
Short-term treatment with SC LMWH, IV UFH, or SC fondaparinux
(Grade 1A)
– LMWH SC once or twice daily over UFH as an outpatient if possible
(Grade 1C) and as an inpatient if necessary (Grade 1A), unless renal
failure (Grade 2C)
– IV UFH: continuous infusion with aPTT monitoring (Grade 1C)
If clinical suspicion of DVT is high, treatment should be initiated
while awaiting results of diagnostic tests (Grade 1C)
Treat for at least 5 d with LMWH, UFH, or fondaparinux until the
INR ≥2.0 for 24 h (Grade 1C)
Start warfarin on first treatment day together with LMWH, UFH, or
fondaparinux (Grade 1A)
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Acute DVT / PE: Duration & Intensity
For transient, reversible risk factor, anticoagulation for at least 3 months (Grade 1A), then evaluate risk-benefit equation for longer treatment (Grade 1C)
For an unprovoked proximal DVT or PE, long-term anticoagulation (Grade 1A)
For a second episode of VTE, long-term anticoagulation (Grade 1A)
For an unprovoked distal DVT, anticoagulation for at least 3 months (Grade 2B)
Warfarin INR target 2.0-3.0, not 3.0-4.0 (both Grade 1A)
For cancer-related VTE, anticoagulation with a LMWH (rather than warfarin) for 3-6 months (Grade 1A), then reassess
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Additional factors that may prompt longer
treatment
Residual significant venous obstruction
Hypercoagulable state(s)
Ongoing estrogenic drugs, thalidomide or lenalidomide
Immobile status
Significantly elevated or rising D-dimers when
anticoagulation is stopped
Patient preference
Acute DVT / PE: Duration & Intensity
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Goals of these procedures
• To reduce acute symptoms
• To reduce risk of postthrombotic syndrome
Eligibility
• Extensive femoral or iliofemoral DVT
• Duration <14 days
• Good performance status
• Low bleeding risk (for thrombolytic therapy)
• Life expectancy >1 year
Acute DVT / PE: Lysis, Thrombectomy, Stents
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Acute DVT / PE:
IVC Interruption
Routine use of an IVC filter as an adjunct to anticoagulation is not advised (Grade 1A)
For proximal DVT, IVC filter indicated if a bleeding risk precludes use of anticoagulation (Grade 1C)
If an IVC filter is placed, the bleeding risk subsides, and anticoagulation is no longer precluded, then anticoagulation is advisable (Grade 1C)
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Calf Vein DVT – Evidence?
• Definition?– Infrapopliteal
– Intramuscular
– Plantar
• Incidence?– Asymptomatic
12%-40%
– Symptomatic 8-49%
• PE?– 0-6.3%
• Propagation?– 4%-15%
• Postthrombotic Syndrome– 8% - 57% C2-C3
– 3%- 5% C4 – C6
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Calf Vein DVT – Evidence?
• Definition?– Nicos
• Incidence?– Nicos
• PE?– Nicos
– Passman
• Propagation– Nicos
• Postthrombotic Syndrome– Nicos
– Passman
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Calf Vein DVTEvidence Based Outcomes
Study DVT
Location
N Treatment F/U DVT
Recurrence
PE
Galanaud et al. Thromb Haemost, 2009
Infrapopliteal 787 81% oral
anticoagulation
3% None
3 months 1.0% 1.1%
Schwartz et al. J
Vasc Surg 2010
Intramuscular 109 Group 1: LMWH 10
days + compression
Group 2: compression
3 months Group 1: 3.7%
Group 2: 3.8%
Group 1: 0%
Group 1: 0%
Baglin et al. J Thormb Haemost 2010
Distal DVT 171 Heparin 5-10 days then
oral anticoagulation 3
months
5 years 6.4% 1.2%
Gillet et al. J Vasc Surg 2007
Intramuscular 131 Oral anticoagulation 1-
3 months +
compression
3 years 18.8% 4.5%
Pinede et al. Circulation 2001
Infrapopliteal 197 Group 1: LMWH or
UFH 12 weeks
Group 2: 6 weeks
LMWH or UFH
15 months Group 1: 2.3%
Group 2: 2.0%
Group 1: 1.1%
Group 2: 0%
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Calf Vein DVT Duration & Intensity
For transient, reversible risk factor, anticoagulation for at least 3 months (Grade 1A), then evaluate risk-benefit equation for longer treatment (Grade 1C)
For an unprovoked proximal DVT or PE, long-term anticoagulation (Grade 1A)
For a second episode of VTE, long-term anticoagulation (Grade 1A)
For an unprovoked distal DVT, anticoagulation for at least 3 months (Grade 2B)
Warfarin INR target 2.0-3.0, not 3.0-4.0 (both Grade 1A)
For cancer-related VTE, anticoagulation with a LMWH (rather than warfarin) for 3-6 months (Grade 1A), then reassess
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Calf Vein DVT Treatment Algorithm
Calf DVT
Infrapopliteal
Unprovoked
Anticoagulation 12 weeks – 3 months then re-evaluate
- Leg sxs
- Respiratory sxs
- PE
Anticoagulation 3 months then re-
evaluate
- Propagation
- Recurrence
Anticoagulation 3 months then re-
evaluate
- Asymptomatic
- Transient, Reversible Risk
Factor
Bleeding Risk Low:
consider anticoagulation vs
surveillance
Bleeding Risk High:
Surveillance
Intramuscular
Surveillance
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Proximal vs Calf DVTConclusion
• Iliofemoral DVT:
– anticoagulation
– consider catheter clot removal options
– compression
• Femoral – Popliteal DVT:
– anticoagulation• transient reversible risk
factor: – 3 months then re-
evaluate
• unprovoked or recurrent: – long-term
– compression
• Calf DVT:
– more evidence needed
– anticoagulation• unprovoked:
– 12 weeks to 3 months
• PE, leg symptoms, recurrence or propagation:
– 3 months then re-evaluate
– surveillance• transient reversible risk
factor
• asymptomatic
• intramuscular
– compression