Transcript VTED Tele-education U of Calgary CME

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
American College of
Chest Physicians
CHEST Supplement
September 2004
Volume 126(3)
**Uptodate & eMedicine
are not recent ***
full text guidelines available to anyone
www.chest.org  supplements
Venothrombotic disease (VTED)
• superficial thrombophlebitis
• deep vein thrombosis
– lower limb
– upper limb
• pulmonary thromboembolism
• post-thrombotic syndrome
Superficial Vein Thrombophlebitis
Superficial Leg Veins  Saphenous (L & S)
Superficial Vein Thrombophlebitis
Superficial Thrombophlebitis
• Presentation
– inflammation along course of vein
– complicates 20% of IV infusions
Superficial Thrombophlebitis
• Conditions Similarly Presenting
– DVT
– cellulitis
– lymphangitis
– panniculitis
– insect bite
– erythema nodosum
– cutaneous polyarteritis nodosa (PAN)
– sarcoid granuloma
– Kaposi's sarcoma
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
• 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
Potentially Lethal Misnomer  SFV = deep
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)
• Exclude DVT among ST patients
• Superficial Femoral Vein is a deep vein
• Spontaneous ST  heparin
• Infusion-related ST  NSAID
Deep Vein Thrombosis
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
• 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
D-dimer screen
Compression Ultrasound
Venography
• (MRI expensive)
• (IPG ‘discredited’)
MRI  Positive for DVT
• sensitivity 100% & specificity 96%
J Vasc Surg 1993 Nov;18(5):734-41
DVT - diagnosis
• Clinical Suspicion - any one feature performs poorly
Well’s DVT Clinical Prediction Rule
•
•
•
•
•
•
•
•
•
Cancer
Paralysis
Bedridden
Tender vein
Leg swollen
Calf swollen
Pitting edema
Collaterals dilated
Alternative dx
1
1
1
1
1
1
1
1
-2
• TOTAL: 3 (high 75%), 1-2 (mod 17%), 0 (low 3%)
Lancet 1997;350:1795-8
Well’s Criteria
- study excluded those with previous VTED, needed
indefinite anti-coagulation, imminent death
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
Pulmonary Thromboembolism
• Diagnosis
– Clinical
– D-dimer
– Ventilation - Perfusion Scan (V/Q scan)
– Spiral CT Scan
– Pulmonary Angiogram
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 diagnosis
• Signs of PE in 117 previously normal patients
–
–
–
–
–
–
–
–
–
–
–
–
tachypnea (20/min)
rales (crackles)
tachycardia (>100/min)
fourth heart sound
increased P2
diaphoresis
temperature >38.5°C
wheezes
Homans' sign
right ventricular lift
pleural friction rub
third heart sound
70%
51
30
24
23
11
7
5
4
4
3
3
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
• Immobilization
1.5
1.5
• Previous DVT or PE
• Hemoptysis
• Malignancy
1.5
1.0
1.0
– bedrest (except access to BR)  3 days OR
– surgery in previous 4 weeks
– 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-Dimer
• Same as PE
PE - diagnosis (V/Q scan)
• high probability V/Q scan (2 defects)
V/Q scan
normal
near normal
 PE ruled out
 PE ruled out
low probability  can’t rule in nor out
indeterminate  can’t rule in nor out
high probability  PE ruled in
Most V/Q Scans are non-diagnostic
PE - diagnosis (spiral CT scan)
Sprial CT Scanning
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
J Emerg Med 2005 Nov;29(4):399-404
409 with negative CT AND negative US
2 of these were diagnosed with DVT (day 37 & 73)
PE - diagnosis
Venography
- gold standard
- (100% / 100%)
CHR Protocol
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
• 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
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
6 Trials Compared Nothing to Heparin
Prevent Trial (Circ 2004)
Dalteparin 5,000 units sq od
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
*dose per weight, *renal failure caution
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
no prophylaxis
DVT
25%
DVT
ASA
20%
elastic stocking 14%
heparin 5000 bid 8%
LMWH
6%
IPC / SCD
3%
all PE
1.6%
Fatal PE
0.9%
No. Patients
372
196
10,339
9,364
132
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 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#
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
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
• Every ACCP Guideline reveals significant
changes.
• Other Topics
– role of Anti-coagulation Management Clinics
– perioperative care
– travel
– intolerance to heparin