Venothrombotic Disease Diagnosis and Treatment

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Venothrombotic DiseaseDiagnosis and Treatment

• Jeffrey P Schaefer, MSc, MD, FRCPC
• January 31, 2006
• slides available www.ucalgary.ca/jpschaef
• guidelines available www.chest.org

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Objectives

• Venothrombotic Disease
• diagnosis
• therapy / prevention

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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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full text guidelines available to
anyonewww.chest.org ? supplements
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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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Superficial Leg Veins ? Saphenous (L S)
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Superficial Vein Thrombophlebitis
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Superficial Thrombophlebitis

• Presentation
• inflammation along course of vein
• complicates 20 of IV infusions

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Superficial Thrombophlebitis

• Conditions Similarly Presenting
• DVT
• cellulitis
• lymphangitis
• panniculitis
• insect bite
• erythema nodosum
• cutaneous polyarteritis nodosa (PAN)
• sarcoid granuloma
• Kaposi's sarcoma

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Superficial Thrombophlebitis

• Diagnosis
• risk factor assessment
• clinical assessment
• inflammation along superficial vein
• rule out DVT
• rule out other conditions

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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 Jun11(6)818-23
• 21 ambulatory ST long saphenous vein ?
• found 7 high probability V/Q scans
• PE 33.3 (95CI 15 to 57)
• clinical PE present in only one
• J Vasc Surg 1999 Dec30(6)1113-5

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• Potentially Lethal Misnomer ? SFV deep

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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

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Take-Home-PointsSuperficial Thrombophlebitis (ST)

• Exclude DVT among ST patients
• Superficial Femoral Vein is a deep vein
• Spontaneous ST ? heparin
• Infusion-related ST ? NSAID

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Deep Vein Thrombosis
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Incidence of DVT and PE

• 117 / 100,000 / year among all
• 900 / 100,000 / year among 85 year olds
• Am Fam Phys 200469(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

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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
• D-dimer screen
• Compression Ultrasound
• Venography
• (MRI expensive)
• (IPG discredited)

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MRI ? Positive for DVT

• sensitivity 100 specificity 96
• J Vasc Surg 1993 Nov18(5)734-41

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DVT - diagnosis

• Clinical Suspicion - any one feature performs
  poorly

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Wells 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 19973501795-8

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Wells Criteria

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

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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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Pulmonary Thromboembolism

• Diagnosis
• Clinical
• D-dimer
• Ventilation - Perfusion Scan (V/Q scan)
• Spiral CT Scan
• Pulmonary Angiogram

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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 100598, 1991

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PE - clinical diagnosis

• Signs of PE in 117 previously normal patients
• tachypnea (20/min) 70
• rales (crackles) 51
• tachycardia (gt100/min) 30
• fourth heart sound 24
• increased P2 23
• diaphoresis 11
• temperature gt38.5C 7
• wheezes 5
• Homans' sign 4
• right ventricular lift 4
• pleural friction rub 3
• third heart sound 3

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Wells 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 gt 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 gt6 (high 78), 2-6 (mod 28), lt 2 (low
  3)
• Thromb Haemost 200083418

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D-Dimer

• Same as PE

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PE - diagnosis (V/Q scan)

• high probability V/Q scan (2 defects)

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V/Q scan

• normal ? PE ruled out
• near normal ? PE ruled out
• low probability ? cant rule in nor out
• indeterminate ? cant rule in nor out
• high probability ? PE ruled in

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Most V/Q Scans are non-diagnostic
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PE - diagnosis (spiral CT scan)
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Sprial CT Scanning
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Helical (Spiral) CT Scan

• 914 ER pts chest pain and dyspnea
• 858 eligible for study
• clinical assessment (Wells) AND D-dimer
• /- Helical CT
• /- Compression Ultrasound
• J Emerg Med 2005 Nov29(4)399-404

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J Emerg Med 2005 Nov29(4)399-404
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• 409 with negative CT AND negative US
• 2 of these were diagnosed with DVT (day 37
  73)

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PE - diagnosis

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

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CHR Protocol
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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)
• 13000 (general population) ? 12000
• risk of sib of leukemic child 1700

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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)

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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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6 Trials Compared Nothing to Heparin
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Prevent Trial (Circ 2004)Dalteparin 5,000 units
sq od
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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
• dose per weight, renal failure caution

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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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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

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Recommendations Gen Surg

• Low Risk
• minor procedure, lt 40 yr, no RF
• aggressive mobilization
• Moderate Risk
• minor procedure with RF
• minor procedure, 40-60yr, no RF
• major surgery lt40
• LDUH, LMWH, ES, or IPC

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Recommendations Gen Surg

• Higher Risk
• minor procedure gt 60 or with RF
• LDUH, LMWH, IPC
• Highest Risk
• ES, IPC/SCD
• PLUS
• LDUH, LMWH

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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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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

• Every ACCP Guideline reveals significant changes.
• Other Topics
• role of Anti-coagulation Management Clinics
• perioperative care
• travel
• intolerance to heparin