DEFINING THE DURATION OF ANTICOAGULATION. HOW LONG TO TREAT A DVT?
VTE & Duration of Anticoagulation
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Transcript of VTE & Duration of Anticoagulation
Disclosure Mark Meissner, M.D.
I have no financial relationship(s) to disclose.
Mark H. Meissner, MD Professor of Surgery
University of Washington School of Medicine
Seattle, WA
VTE & Duration of Anticoagulation
DVT – Duration of Treatment ACCP Guidelines, Chest 2008
• Duration of anticoagulation guided by randomized trials
• RCT endpoints
• Recurrent VTE
• Bleeding
• 2008 recommendations
• Reversible factors – VKA for 3 months (1A)
• Unprovoked DVT
First episode – VKA for 3 months (1A) with re-evaluation for long-
term treatment (1C)
Second episode – Long-term treatment (1A)
Isolated calf thrombosis – VKA for 3 months (2B)
• Cancer – LMWH for 3 – 6 months (1A) , subsequent
LMWH or VKA indefinitely or until cancer resolved (1C)
But Are The Guidelines Always Helpful?
What does “assess for long-term” anticoagulation
REALLY mean?
Do You Test For Thrombophilia?
Undefined - 28%
Factor V - 20%
Factor VIII - 16%
Hyperhomocysteinemia
10%
APLA - 10%
Prothrombin 20210A
6%
Protein C - 5%
Protein S - 3%
AT III - 1%
Disfibrinogenemia - 1%
Risk & Incidence of a First DVT Bauer KA, Ann Intern Med 2001
Variable Relative Risk Annual Incidence
Normal 1 0.008
Hyperhomocysteinemia 2.5 0.02
Homozygous MTHFR 1 0.008
Prothrombin G20210A 2.8 0.02
Oral Contraceptive Use 4 0.03
Heterozygous FV Leiden 3 - 7 0.06
Homozygous FV Leiden 80 0.5 - 1
Factor VIII > 150% 4.8 0.04
AT, Protein C Deficiency 7.3 – 15
Protein S Deficiency 2
Blood Group A 1.9 – 3.2
Recurrent Idiopathic VTE Kearon et al, New Engl J Med 1999
Recurrent VTE (p < 0.001)
Warfarin group - 1.3% / patient-year
Placebo - 27.4% / patient-year
Defect Recurrence
(n = 17)
No Recurrence
(n = 66)
p
V Leiden 19% 29% ns
G20210A 6% 3% ns
APL Antibody 25% 3% 0.03
Warfarin X 3 mo Warfarin X 24 mo (n = 79)
Placebo X 24 mo (n = 83)
History a better predictor than genetic tests
Thrombophilia and Recurrent VTE Simpson EL, Health Technology Assessment 2009
Thrombophilia Incidence in VTE
(%)
Recurrence
(RR)
Change in
Management
FVL Heterozygous 10 – 50% 1.0 No
PTG20210A Heterozygous 5 – 18% 1.48 No
FVL / 20210A Heterozygous - 5.4 Yes
Antiphospholipid Antibodies 5.4% 6.8 Yes
Hyperhomocysteinemia 5.7 - 35% 2.7 Yes
Antithrombin 0.5 – 3% Yes
Protein C Deficiency 3 – 5% 1.44 No
Protein S Deficiency 1 – 5% 1.44 No
Most common defects not associated with significant recurrence
Attributable risk – 9% (1 in 10 recurrent VTE events)
Absence of defect ≠ Absence of thrombophilia
The Thrombophilic Phenotype
Venous thromboembolism Onset at young age (< age 50) Recurrent thrombotic events Family history of VTE DVT at unusual anatomic sites Unprovoked idiopathic DVT
Recurrent 2nd and 3rd trimester pregnancy loss Complications of pregnancy
Preeclampsia Abruptio placenta Intrauterine growth retardation
?? Aseptic necrosis of femoral head
Is Ultrasound Useful? Prandoni et al, Ann Intern Med 2009
• Ultrasound at 3, 9, 15, and 21 months
• Compression of common femoral & popliteal veins
• Recanalization – Single diameter < 2mm or serial diameters < 3mm
• Recurrent VTE (33 mo) in 17.8% (Fixed AC) versus 12.3% (Flexible AC)
• Secondary DVT - HR 0.81 (95% CI 0.32 – 2.06)
• Idiopathic DVT – HR 0.61 (95% CI 0.36 – 1.02)
• No significant difference in major bleeding
• 538 patients randomized
• Fixed duration AC
Secondary DVT – 3 mo
Idiopathic DVT – 6 mo
• Flexible duration AC
Secondary – Up to 12 mo
Idiopathic – Up to 24 months
What Did These Trials Measure?
Author Criteria for Recanalization
Prandoni 2009 Single D2 < 2 mm, Serial D2 < 3 mm
Siragusa 2008 D2 < 40% D1
THROMBUS
THROMBUS
THROMBUS
THROMBUS
UNCOMPRESSED
PROBE COMPRESSION
D1
D2
Point measurements in common femoral & popliteal veins
Residual Thrombus No Residual Thrombus
Residual Venous Obstruction (RVO) & D-Dimer Cosmi et al; Thromb Haemost 2005
• 400 patient with first idiopathic DVT
• 6 months anticoagulation recommended
• Compression U/S at AC withdrawal
• D-Dimer (nl < 500) 30 days after AC withdrawal
Recurrence Hazard Ratio p
(-) D-dimer; (-) RVO 5.7% 1 (reference)
(-) D-dimer; (+) RVO 10.4% 1.66 (0.6 - 4.8) .35
(+) D-dimer; (-) RVO 22.9% 4.3 (1.56 - 11.88) .005
(+) D-dimer; (+) RVO 25.9% 4.76 (1.78 - 12.8) .002
RVO does not independently predict recurrence
D-Dimer & Anticoagulant Duration Palareti et al; N Engl J Med 2006
• 608 pts with first idiopathic DVT
• D-dimer 30 days after anticoagulants discontinued
• Normal - 385 (63%)
• Abnl - 223 (47%)
No anticoagulation - 120
Anticoagulation - 103
• Mean f/u - 1.4 years
• Recurrent VTE + Bleeding
• Nl D-dimer - 6.2%
• Abnl D-dimer (anticoag) - 2.9%
• Abnl D-dimer (no anticoag) - 15.0%
Conclusions - Duration of Anticoagulation
Currently determined by trials balancing recurrent VTE and bleeding
Unprovoked calf vein thrombosis – 3 months
Reversible risk factors – 3 months
Unprovoked DVT
1st episode – Assess risk versus benefits after 3 months
2nd episode – Long-term treatment
Selective thrombophilia testing may be warranted but …
Absence of identified defect ≠ absence of thrombophilia
Limited positive predictive value for recurrence
History is the most important determinant of prognosis
Persistent thrombus on U/S (at least in U.S) is not validated
Promising role for D-dimer