Management of DVT (and a little bit of PE, too)

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Management of DVT(and a little bit of PE, too)

• Jeffrey P Schaefer MSc MD FRCPC
• May 24, 2006

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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

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Data Sources - Therapy

• American College of Chest Physicians
• CHEST Supplement
• September 2004
• Volume 126(3)
• Uptodate eMedicine are not recent

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Grade 1 Recommend
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Grade 2 Suggest
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Hierarchy of Evidence therapy/prevention

• Systematic reviews of RCTs
• A single RCT
• Systematic review of observational studies
• Physiological studies
• Unsystematic clinical observations

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Randomized Clinical Trial
Patients with DVT
random allocation
Treatment A
Treatment B
Outcome among A
Outcome among B
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Venothrombotic disease (VTED)

• superficial thrombophlebitis
• deep vein thrombosis
• lower limb
• upper limb
• pulmonary thromboembolism
• post-thrombotic syndrome

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Superficial Vein Thrombophlebitis
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• Potentially Lethal Misnomer ? SFV deep

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Deep Vein Thrombosis
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Calgary Health RegionJan 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

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Calgary Health RegionJan 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

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DVT - diagnosis

• Clinical Suspicion - any one feature performs
  poorly

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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

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Duplex Ultrasonography

• Duplex US
• above knee DVT

• Sens 96
• Spec 96
• Haemostasis 2361-7
• calf dvt
• sens 80

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Venography

• Gold standard (sens 100, spec 100)

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CHR Protocol
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Pulmonary Thromboembolism
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PE - diagnosis (V/Q scan)

• high probability V/Q scan (2 defects)

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PE - diagnosis (spiral CT scan)
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PE - diagnosis

• Venography
• - gold standard
• - (100 / 100)

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CHR Protocol
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Overview of Prevention / Treatment
DVT
PE
Patient at Risk
Death
Prevent DVT
Treat PE Prevent More PE
Treat DVT Prevent PE
Treat PE
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Overview of Prevention / Treatment
Patient at Risk
Prevent DVT
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Risk of VTED among Non-prophylaxed Inpatients
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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)

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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

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How LMWHs Differ - Molecular Weight Distribution
Enoxaparin
UFH
Tinzaparin
2
3
4.5
6.5
15
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Molecular Weight (KDa)
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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

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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

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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

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THR, TKR, Hip, No Prophylaxis

• Prox DVT PE Fatal PE
• THR 23-36 0.7-30 0.1-0.4
• TKR 9-20 9-20 0.2-0.7
• Hip 17-36 4-24 3.6-12.9

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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

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Other Surgical Settings

• Consult CHEST supplement

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Take-Home-PointsDiagnosis of DVT and PE

• Prevention is standard of care.
• Guidelines are explicit.
• medical
• surgical

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Overview of Prevention / Treatment
DVT
PE
Patient at Risk
Death
Prevent DVT
Treat PE Prevent More PE
Treat DVT Prevent PE
Treat PE
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Overview of Prevention / Treatment
DVT
PE
Treat PE Prevent More PE
Treat DVT Prevent PE
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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

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Suspected DVT

• If high clinical suspicion of DVT, treat with
  anticoagulants while awaiting the outcome of
  diagnostic tests (1C).

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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)

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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

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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 gt 3 months
• first idiopathic DVT/PE gt 6 months
• recurrent DVT/PE gt 12 months
• continuing risk factor gt 12 months
• cancer and thrombophilias
• local tendency to tx PE x 6 months

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Thrombolysis for DVT?
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Thrombolysis for DVT?
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Thrombolysis for DVT?
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Therapy Do we need to anticoagulate patients
with acute VTE ?

• Barrit and Jordan, Lancet 196011309
• Randomized trial of no-therapy vs subcutaneous
  heparin for patients with suspected acute PE
• Established the precedent for randomized trials
  in this area

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Is this enough ?
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Do you need a fast acting a/c up front ?

• Brandjes et al. NEJM 19923271485
• Patients with objectively proven acute lower-limb
  DVT
• Randomized trial of IV standard heparin oral
  anticoagulants or oral anticoagulants alone

Symptomatic recurrences
Asymptomatic recurrences
OAC alone
12 / 60
39.6
Heparin OAC
4 / 60
8.2
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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

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Arm DVT

• Many recommendations
• anticoagulation
• thrombolysis
• surgical extraction
• catheter embolectomy
• Latter three interventions ? science not
  persuasive
• JPS ? I treat these similar to leg DVT

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Take-Home-PointsTreatment 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

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Overview of Prevention / Treatment
DVT
PE
Patient at Risk
Death
Prevent DVT
Treat PE Prevent More PE
Treat DVT Prevent PE
Treat PE
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Overview of Prevention / Treatment
PE
Death
Treat PE
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Massive PE

• Thrombolytic Therapy
• highly individualized
• ICU admission
• reserved for echocardiographic right heart failure

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Thrombolysis for sub-massive PE

• n 238
• Endpoint escalation of therapy or death.
  NEJM 20023471143

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Thrombolysis for sub-massive PE
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Post-Thrombotic Syndrome

• Variously defined
• pain and swelling post-DVT
• 20 50

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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)

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What are rutosides?

• A substance produced from leaves flowers of the
  plant Sophora japonica

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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

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What happens to the Thrombus?
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Summary

• ACCP Guidelines
• accessible
• address most situations
• Other Topics
• role of Anti-coagulation Management Clinics
• perioperative care
• travel
• intolerance to heparin

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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
Josephs Healthcare Hamilton, Ontario, Canada
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Thanks to Borys Sydoruk
LEO Pharma Inc.