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Venothrombotic Disease Diagnosis and Treatment. Jeffrey P Schaefer, MSc, MD, FRCPC January 31, 2006 slides available: www.ucalgary.ca/~jpschaef guidelines available: www.chest.org. Objectives. Venothrombotic Disease diagnosis therapy / prevention. Data Sources - Therapy.

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venothrombotic disease diagnosis and treatment

Venothrombotic DiseaseDiagnosis and Treatment

Jeffrey P Schaefer, MSc, MD, FRCPC

January 31, 2006

slides available: www.ucalgary.ca/~jpschaef

guidelines available: www.chest.org

objectives
Objectives
  • Venothrombotic Disease
    • diagnosis
    • therapy / prevention
data sources therapy
Data Sources - Therapy

American College of Chest Physicians

CHEST Supplement

September 2004

Volume 126(3)

**Uptodate & eMedicine are not recent ***

venothrombotic disease vted
Venothrombotic disease (VTED)
  • superficial thrombophlebitis
  • deep vein thrombosis
    • lower limb
    • upper limb
  • pulmonary thromboembolism
  • post-thrombotic syndrome
superficial thrombophlebitis
Superficial Thrombophlebitis
  • Presentation
    • inflammation along course of vein
    • complicates 20% of IV infusions
superficial thrombophlebitis10
Superficial Thrombophlebitis
  • Conditions Similarly Presenting
    • DVT
    • cellulitis
    • lymphangitis
    • panniculitis
    • insect bite
    • erythema nodosum
    • cutaneous polyarteritis nodosa (PAN)
    • sarcoid granuloma
    • Kaposi's sarcoma
superficial thrombophlebitis11
Superficial Thrombophlebitis
  • Diagnosis
    • risk factor assessment
    • clinical assessment
      • inflammation along superficial vein
    • rule out DVT***
    • rule out other conditions
superficial thrombophlebitis and deep vein thrombosis
Superficial Thrombophlebitis and Deep Vein Thrombosis
  • 42 leg ST without clinical DVT 
    • found 4 above knee DVTs and 1 below knee DVT
    • DVT 12%

J Vasc Surg 1990 Jun;11(6):818-23

  • 21 ambulatory ST long saphenous vein 
    • found 7 high probability V/Q scans
    • PE = 33.3% (95%CI: 15 to 57)
    • clinical PE present in only one

J Vasc Surg 1999 Dec;30(6):1113-5

superficial thrombophlebitis tx
Superficial Thrombophlebitis Tx
  • Complication of Infusion
    • topical or oral NSAID
    • warmth / elevation
  • Spontaneous Superficial Thrombophlebitis
    • intermediate dosages of UFH or LMWH for at least 4 weeks
    • JPS  dalteparin 5,000 sq od x 4 wks for most, consider full dose tinzaparin if severe
take home points superficial thrombophlebitis st
Take-Home-PointsSuperficial Thrombophlebitis (ST)
  • Exclude DVT among ST patients
  • Superficial Femoral Vein is a deep vein
  • Spontaneous ST  heparin
  • Infusion-related ST  NSAID
incidence of dvt and pe
Incidence of DVT and PE
  • 117 / 100,000 / year among all
  • 900 / 100,000 / year among 85 year olds

Am Fam Phys 2004;69(12):2829-36

  • Alberta 2005 Population (3.2 m)
    • 3,223,400 x 117 / 100,000 = 3,771 VTEDS/yr
    • 3,223,400 x $400 = $1,289,360,000
calgary health region jan 1 to june 30 2001
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
calgary health region jan 1 to june 30 200119
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: $1,500,000QIHI
dvt diagnosis
DVT - diagnosis
  • Clinical Suspicion
  • D-dimer screen
  • Compression Ultrasound
  • Venography
  • (MRI expensive)
  • (IPG ‘discredited’)
mri positive for dvt
MRI  Positive for DVT
  • sensitivity 100% & specificity 96%

J Vasc Surg 1993 Nov;18(5):734-41

dvt diagnosis22
DVT - diagnosis
  • Clinical Suspicion - any one feature performs poorly
well s dvt clinical prediction rule
Well’s DVT Clinical Prediction Rule
  • Cancer 1
  • Paralysis 1
  • Bedridden 1
  • Tender vein 1
  • Leg swollen 1
  • Calf swollen 1
  • Pitting edema 1
  • Collaterals dilated 1
  • Alternative dx - 2
  • TOTAL: 3 (high 75%), 1-2 (mod 17%), 0 (low 3%)

Lancet 1997;350:1795-8

well s criteria
Well’s Criteria

- study excluded those with previous VTED, needed indefinite anti-coagulation, imminent death

d dimer
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 Ultrasonography
  • Duplex US
    • above knee DVT
  • Sens = 96%
  • Spec = 96%

Haemostasis 23:61-7

  • calf dvt
    • sens = 80%
venography
Venography
  • Gold standard (sens 100%, spec 100%)
pulmonary thromboembolism30
Pulmonary Thromboembolism
  • Diagnosis
    • Clinical
    • D-dimer
    • Ventilation - Perfusion Scan (V/Q scan)
    • Spiral CT Scan
    • Pulmonary Angiogram
pe clinical diagnosis
PE - clinical diagnosis
  • Symptoms of PE in 117 previously normal patients
    • dyspnea 73%
    • pleuritic pain 66
    • cough 37
    • leg swelling 28
    • leg pain 26
    • hemoptysis 13
    • palpitations 10
    • wheezing 9
    • angina-like pain 4 Chest 100:598, 1991
pe clinical diagnosis32
PE - clinical diagnosis
  • Signs of PE in 117 previously normal patients
    • tachypnea (20/min) 70%
    • rales (crackles) 51
    • tachycardia (>100/min) 30
    • fourth heart sound 24
    • increased P2 23
    • diaphoresis 11
    • temperature >38.5°C 7
    • wheezes 5
    • Homans' sign 4
    • right ventricular lift 4
    • pleural friction rub 3
    • third heart sound 3
well s pe clinical prediction rule
Well’s PE Clinical Prediction Rule
  • Signs/Symptoms of DVT 3.0
    • measured leg swelling AND
    • pain with palpation in the deep vein region
  • Alternative diagnoses less likely than PE 3.0
    • history, physical exam, chest X-ray, EKG, lab results
  • Pulse > 100 beats/min 1.5
  • Immobilization 1.5
    • bedrest (except access to BR)  3 days OR
    • surgery in previous 4 weeks
  • Previous DVT or PE 1.5
  • Hemoptysis 1.0
  • Malignancy 1.0
    • receiving active treatment for cancer OR
    • have received treatment for cancer within the past 6 months OR
    • are receiving palliative care for cancer
  • TOTAL: >6 (high 78%), 2-6 (mod 28%), < 2 (low 3%)

Thromb Haemost 2000;83;418

d dimer35
D-Dimer
  • Same as PE
pe diagnosis v q scan
PE - diagnosis (V/Q scan)
  • high probability V/Q scan (2 defects)
v q scan
V/Q scan

normal  PE ruled out

near normal  PE ruled out

low probability  can’t rule in nor out

indeterminate  can’t rule in nor out

high probability  PE ruled in

helical spiral ct scan
Helical (Spiral) CT Scan
  • 914 ER pts: chest pain and dyspnea
  • 858 eligible for study
  • clinical assessment (Well’s) AND D-dimer
  • +/- Helical CT
  • +/- Compression Ultrasound

J Emerg Med 2005 Nov;29(4):399-404

slide43
409 with negative CT AND negative US

2 of these were diagnosed with DVT (day 37 & 73)

pe diagnosis
PE - diagnosis

Venography

- gold standard

- (100% / 100%)

pregnancy
Pregnancy
  • Ionizing Radiation Exposure
    • first 8 weeks has highest risk for in utero death
    • most frequent abnormality is microcephaly / mental retardation among term infants
    • 8 to 15 wk most sensitive period for retardation
    • risk of severe mental retardation
      • 4% for 10 rad
      • 60% for 150 rad
    • relative risk of childhood leukemia
      • RR = 1.5 – 2.0 (1 – 2 rad exposure)
      • 1:3000 (general population)  1:2000
      • risk of sib of leukemic child 1:700
take home points diagnosis of dvt and pe
Take-Home-PointsDiagnosis of DVT and PE
  • Multimodal approach
    • Clinical
    • D-dimer
    • US / VQ / Spiral CT
  • Studies exclude those with previous VTED
  • Fetal risk is low but anxiety may be high (having numbers is helpful)
overview of prevention treatment
Overview of Prevention / Treatment

Patient at Risk

DVT

PE

Death

Prevent DVT

Treat DVT =

Prevent PE

Treat PE =

Prevent

More PE

Treat PE

overview of prevention treatment51
Overview of Prevention / Treatment

Patient at Risk

Prevent DVT

vted prevention in medical pts
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
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

*dose per weight, *renal failure caution

warfarin
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
general surgery
General Surgery

DVT all PE Fatal PE

no prophylaxis 25% 1.6% 0.9%

DVT No. Patients

ASA 20% 372

elastic stocking 14% 196

heparin 5000 bid 8% 10,339

LMWH 6% 9,364

IPC / SCD 3% 132

recommendations gen surg
Recommendations: Gen Surg
  • Low Risk
    • minor procedure, < 40 yr, no RF
    • aggressive mobilization
  • Moderate Risk
    • minor procedure with RF
    • minor procedure, 40-60yr, no RF
    • major surgery <40
    • LDUH, LMWH, ES, or IPC
recommendations gen surg60
Recommendations: Gen Surg
  • Higher Risk
    • minor procedure > 60 or with RF
    • LDUH, LMWH, IPC
  • Highest Risk
    • ES, IPC/SCD

PLUS

    • LDUH, LMWH
thr tkr hip no prophylaxis
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

recommendations thr tkr hip
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
Other Surgical Settings
  • Consult CHEST supplement
take home points diagnosis of dvt and pe64
Take-Home-PointsDiagnosis of DVT and PE
  • Prevention is standard of care.
  • Guidelines are explicit.
    • medical
    • surgical
overview of prevention treatment65
Overview of Prevention / Treatment

Patient at Risk

DVT

PE

Death

Prevent DVT

Treat DVT =

Prevent PE

Treat PE =

Prevent

More PE

Treat PE

overview of prevention treatment66
Overview of Prevention / Treatment

DVT

PE

Treat DVT =

Prevent PE

Treat PE =

Prevent

More PE

why intervene
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
Suspected DVT
  • If high clinical suspicion of DVT, treat with anticoagulants while awaiting the outcome of diagnostic tests (1C+).
confirmed dvt pe
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
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
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: > 3 months*
    • first idiopathic DVT/PE: > 6 months
    • recurrent DVT/PE: > 12 months
    • continuing risk factor > 12 months
      • cancer and thrombophilias

*local tendency to tx PE x 6 months

calf below knee dvt
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
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
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
overview of prevention treatment75
Overview of Prevention / Treatment

Patient at Risk

DVT

PE

Death

Prevent DVT

Treat DVT =

Prevent PE

Treat PE =

Prevent

More PE

Treat PE

massive pe
Massive PE
  • Thrombolytic Therapy
    • highly individualized
    • ICU admission
    • reserved for echocardiographic right heart failure
thrombolysis for sub massive pe
Thrombolysis for sub-massive PE

n = 238

Endpoint = escalation of therapy or death. NEJM 2002;347;1143

post thrombotic syndrome
Post-Thrombotic Syndrome
  • Variously defined
    • pain and swelling post-DVT
    • 20 – 50%
post phlebetic syndrome
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
What are rutosides?
  • A substance produced from leaves & flowers of the plant Sophora japonica
what to expect
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
summary
Summary
  • Every ACCP Guideline reveals significant changes.
  • Other Topics
    • role of Anti-coagulation Management Clinics
    • perioperative care
    • travel
    • intolerance to heparin