Transcript VTED Tele-education U of Calgary CME

Management of DVT
(and a little bit of PE, too)
Jeffrey P Schaefer MSc MD FRCPC
May 24, 2006
Objectives
• Management of Venothrombotic Disease
– levels of evidence
– epidemiology and diagnostics
– initial management of suspected DVT
– management of confirmed DVT
– special populations
– post-thrombotic syndrome
Data Sources - Therapy
American College of
Chest Physicians
CHEST Supplement
September 2004
Volume 126(3)
**Uptodate & eMedicine
are not recent ***
Grade 1 “Recommend”
Grade
Risk/
Benefit
Methodologic Strength
Strength of
Recommendation
1A
Clear
RCTs w/o significant
limitations
Strong; applies to most
patients and circumstances
1C+
Clear
No RCTs; strong results
extrapolated or strong
observational studies
Strong; most patients,
circumstances
1B
Clear
RCTs with limitations
Strong; most patients
1C
Clear
Observational studies
Intermediate
Grade 2 “Suggest”
Grade
Risk/
Benefit
Methodologic Strength
Strength of
Recommendation
2A
Unclear
RCTs w/o important limitations Intermediate; action depends
on circumstances, values
2C+
Unclear
No RCTs; strong results
extrapolated or strong
observational studies
Weak; action depends on
circumstances, values
2B
Unclear
RCTs with limitations
Weak; alternatives likely
better for some
2C
Unclear
Observational studies
Very weak
Hierarchy of Evidence:
therapy/prevention
• Systematic reviews of RCTs
• A single RCT
• Systematic review of observational
studies
• Physiological studies
• Unsystematic clinical observations
Randomized Clinical Trial
Patients with DVT
random allocation
Treatment A
Treatment B
Outcome among A
Outcome among B
Venothrombotic disease (VTED)
• superficial thrombophlebitis
• deep vein thrombosis
– lower limb
– upper limb
• pulmonary thromboembolism
• post-thrombotic syndrome
Superficial Vein Thrombophlebitis
Potentially Lethal Misnomer  SFV = deep
Deep Vein Thrombosis
Calgary Health Region
Jan 1 to June 30, 2001
• 1,400 patients investigated for DVT
– 33% inpatient
– 40% emergency dept
– 27% outpatient
• 3,175 patients investigated for PE
– 60% inpatient
– 25% emergency dept
– 15% outpatient
QIHI
Calgary Health Region
Jan 1 to June 30, 2001
• DVT tests
– 4,200 leg ultrasounds
• 2,500 bilateral
• 1,700 unilateral
– 95 venograms
• PE tests
– 1,400 V/Q scans
– 130 CT scans
– 100 pulmonary angiograms
• Estimated cost:
$1,500,000
QIHI
DVT - diagnosis
• Clinical Suspicion - any one feature performs poorly
D - dimer
• D-dimer Assay
– D-dimer is breakdown product of fibrinolysis
– high sensitivity (98%) & modest specificity (~50%)
– useful for excluding DVT and PE
– not useful for confirming diagnosis
– SHOULD NOT TO BE USED
• post-operative patient
• pregnant patient
• patient with malignancy
Duplex Ultrasonography
• Duplex US
– above knee DVT
• Sens = 96%
• Spec = 96%
Haemostasis 23:61-7
• calf dvt
– sens = 80%
Venography
• Gold standard (sens 100%, spec 100%)
CHR Protocol
Pulmonary Thromboembolism
PE - diagnosis (V/Q scan)
• high probability V/Q scan (2 defects)
PE - diagnosis (spiral CT scan)
PE - diagnosis
Venography
- gold standard
- (100% / 100%)
CHR Protocol
Overview of Prevention / Treatment
Patient at
Risk
Prevent DVT
DVT
Treat DVT =
Prevent PE
PE
Treat PE =
Prevent
More PE
Death
Treat PE
Overview of Prevention / Treatment
Patient at
Risk
Prevent DVT
Risk of VTED among
Non-prophylaxed Inpatients
VTED Prevention in Medical Pts
• Medical in-patients
– heart failure, severe resp disease, bedridden,
cancer, prev VTE, sepsis, acute neurologic
disease, or inflammatory bowel disease
• recommend LDUH (1A) or LMWH (1A)
• if heparin contraindication, use mechanical
prophylaxis with GCS or IPC (1C+)
Heparins
• Dalteparin (Fragmin)
– primarily used for prevention
– 2,500 to 5,000 units sq od
• Tinzaparin (Innohep)
– primarily used for DVT / PE therapy
– 175 anti-Xa units / kg sq od
• Enoxaparin (Lovenox)
– primarily used for acute coronary syndromes
How LMWHs Differ - Molecular
Weight Distribution
Enoxapar
Tinzapari
in
n
2
3
4.
5
6.5
UFH
15
Molecular Weight (KDa)
3
0
LMWH: Doses
• Treatment: DVT or PE
– Tinzaparin 175 u/kg sc OD
– Dalteparin 200 u/kg sc OD or 100 u/kg sc BID
– Enoxaparin 1.5 mg/kg sc OD or 1 mg/kg sc BID
• Prophylaxis
– Dalteparin 5000 u sc OD (2500 day of Orthopedic
surgery)
– Enoxaparin 30 mg sc BID or 40 mg sc OD
– Tinzaparin weight based or 4500 u sc OD
What of those pre-filled syringes
• “Pre-filled syringes” are not
useful as they do not allow me
to exactly dose the patient
• Dose adjustment is likely
unneeded as these drugs
have a wide therapeutic
window
– e.g. if the predicted dose is 12764 U I
would feel very comfortable treating
with 14000 unit pre-filled syringe
• What if my assurances are not
enough ?
– Heparin is stable for some days if
drawn up into a syringe by clinic staff
and given to the patient
Warfarin
• Inhibits the formation of Vitamin K dependent
clotting factors 2, 7, 9, 10
• Inhibits formation of Protein C and S
• Overall, defective clotting proteins are formed
• Effect depends on depletion of previously
made normal clotting proteins (2, 7, 9, 10)
• Not safe in pregnancy
THR, TKR, Hip#, No Prophylaxis
THR
TKR
Hip#
Prox DVT%
23-36
9-20
17-36
PE%
0.7-30
9-20
4-24
Fatal PE%
0.1-0.4
0.2-0.7
3.6-12.9
Recommendations: THR, TKR, Hip#
• LMWH started
– 12 hr pre-op or (epidural hematoma risk)
– 12-24 hr post-op or
– 4-6 hr post-op at 1/2 dose
or
• Warfarin started
– immediately pre-op
– post-op
• Extended (post-discharge) may be acceptable
Other Surgical Settings
• Consult CHEST supplement
Take-Home-Points
Diagnosis of DVT and PE
• Prevention is standard of care.
• Guidelines are explicit.
– medical
– surgical
Overview of Prevention / Treatment
Patient at
Risk
Prevent DVT
DVT
Treat DVT =
Prevent PE
PE
Treat PE =
Prevent
More PE
Death
Treat PE
Overview of Prevention / Treatment
DVT
Treat DVT =
Prevent PE
PE
Treat PE =
Prevent
More PE
Why Intervene?
• Risk of PE among untreated DVT ~ 15-25%
• Risk of death among PE ~ 20-30%
• Risk of death among untreated DVT ~5%
• Risk of death for treated PE ~ 1.5%/yr
• Risk of death for treated DVT ~ 0.4%/yr
• Risk of major bleed treated PE/DVT ~1.0%/yr
Suspected DVT
• If high clinical suspicion of DVT, treat with
anticoagulants while awaiting the outcome of
diagnostic tests (1C+).
Confirmed DVT/PE
• Clinical assessment risk / benefit of intervetion.
• Draw baseline CBC, PTT, and INR and start:
Low Molecular Weight Heparin
or
Adjusted Dose Unfractionated Heparin IV
or
Adjusted Dose Unfractionated Heparin SQ
Any one of the three are acceptable
Low Molecular Wt Heparin is preferred
(dosing, slightly better efficacy and safety)
Duration of Heparin for acute DVT/PE
• Most Adults
– minimum 5 days AND
– until INR therapeutic for two consecutive days
• Active Cancer
– minimum 3 – 6 months before converting to
‘indefinite’ warfarin
• Pregnant
– therapeutic heparin until delivery
– warfarin 4-6 weeks post-partum
Duration of Warfarin for DVT/PE
• Warfarin (if not pregnant)
– start concurrently with heparin
– target INR 2.0 - 3.0
• Duration of warfarin
– time reversible risk factors:
– first idiopathic DVT/PE:
– recurrent DVT/PE:
– continuing risk factor
> 3 months*
> 6 months
> 12 months
> 12 months
• cancer and thrombophilias
*local tendency to tx PE x 6 months
Thrombolysis for DVT?
Thrombolysis for DVT?
Thrombolysis for DVT?
Therapy: Do we need to anticoagulate
patients with acute VTE ?
Barrit and Jordan, Lancet 1960:1:1309
• Randomized trial of no-therapy vs subcutaneous
heparin for patients with suspected acute PE
• Established the precedent for randomized trials in
this area
Non-fatal
Deaths recurrences
Untreated 5
Treated
0
5
0
Is this enough ?
Do you need a fast acting a/c up front ?
Brandjes et al. NEJM 1992:327;1485
– Patients with objectively proven acute lower-limb DVT
– Randomized trial of IV standard heparin + oral
anticoagulants or oral anticoagulants alone
Symptomatic Asymptomatic
recurrences
recurrences
OAC alone
Heparin + OAC
12 / 60
39.6 %
4 / 60
8.2 %
Calf (below knee) DVT
• Below knee DVT  extend proximally in 20%
of patients treated with IV heparin for several
days
• Recommend: treatment of below knee DVT is
SAME AS proximal DVT
Arm DVT
• Many recommendations
– anticoagulation
– thrombolysis
– surgical extraction
– catheter embolectomy
Latter three interventions  science not persuasive
JPS  I treat these similar to leg DVT
Take-Home-Points
Treatment of DVT and PE
• Heparin
– low molecular weight is preferred
– duration is longer among cancer patients
• Warfarin
– duration varies by clinical setting
– implicit message that longer is better
Overview of Prevention / Treatment
Patient at
Risk
Prevent DVT
DVT
Treat DVT =
Prevent PE
PE
Treat PE =
Prevent
More PE
Death
Treat PE
Overview of Prevention / Treatment
PE
Death
Treat PE
Massive PE
• Thrombolytic Therapy
– highly individualized
– ICU admission
– reserved for echocardiographic right heart failure
Thrombolysis for sub-massive PE
n = 238
Endpoint = escalation of therapy or death. NEJM 2002;347;1143
Thrombolysis for sub-massive PE
Post-Thrombotic Syndrome
•
Variously defined
– pain and swelling post-DVT
– 20 – 50%
Post-Phlebetic Syndrome
• elastic compression stocking (30-40) during
2 years after an episode of DVT (1A)
• intermittent pneumatic compression for
severe edema (2B)
• elastic compression stockings for mild
edema of the leg due to the PTS (2C).
-------------• Rutosides for mild edema due to PTS (2B)
What are rutosides?
• A substance produced from leaves & flowers
of the plant Sophora japonica
What to expect?
• Potential for post-phlebitic syndrome
• PE chest pain may come and go
• Hemoptysis may occur
• Elevate legs when not ambulating
• Okay to walk
What happens to the Thrombus?
Summary
• ACCP Guidelines
– accessible
– address most situations
• Other Topics
– role of Anti-coagulation Management Clinics
– perioperative care
– travel
– intolerance to heparin
Anticoagulation in Special Risk
Populations
Mark Crowther, MD, MSc, FRCPC
Associate Professor, Medicine and Haematology Residency
Training Program Director
Acting Vice President, Research and Head of Service,
Haematology
St Joseph’s Healthcare
Hamilton, Ontario, Canada
Thanks to Borys Sydoruk
LEO Pharma Inc.