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Stephan Moll, MD University of North Carolina Chapel Hill, N.C. Dept. of Medicine, Heme-Onc smoll@med.unc Tel: 919-966-3 - PowerPoint PPT Presentation


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Venous Thromboembolism. Stephan Moll, MD University of North Carolina Chapel Hill, N.C. Dept. of Medicine, Heme-Onc smoll@med.unc.edu Tel: 919-966-3311 Richmond 9/29/2006. A. Diagnosis. Clinical assessment. D-dimer. B. Treatment. LMWH, Fondaparinux, unfract. Heparin.

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slide1

Venous Thromboembolism

Stephan Moll, MD

University of North Carolina

Chapel Hill, N.C.

Dept. of Medicine, Heme-Onc

smoll@med.unc.edu

Tel: 919-966-3311

Richmond

9/29/2006

slide2

A. Diagnosis

Clinical assessment

D-dimer

B. Treatment

LMWH, Fondaparinux, unfract. Heparin

Outpatient versus inpatient

Length of warfarin

postthrombotic syndrome

C. Other

Education resources

Overview

slide3

Case - History

  • HPI
  • 28 yr old woman with
  • left calf pain x 1 week
  • noticeable left ankle + thigh swelling
  • started without trigger
  • PMH
  • appendectomy age 16
  • obesity (BMI 32.0)
  • Family Hx
  • Large family
  • Maternal grandmother: “clot in her leg at 63”
  • Meds
  • Yasmin®
slide4

L > R by 4 cm

L > R by 2.5 cm

Case – Physical Examination

slide5

Pre-test Probability - DVT

  • Clinical characteristics (Well’s criteria):
  • Active cancer
  • Paralysis or plaster immobilization
  • Bedridden ≥ 3 d; major surgery in 3 mo
  • Entire leg swollen
  • Calf swelling > 3cm
  • Pitting edema in affected leg
  • Collateral non-varicose superficial veins
  • Localized tenderness along deep veins
  • Previous DVT
  • Alternative dx more likely

1

1

1

1

1

1

1

1

1

-2

  • score < 2: DVT unlikely
  • score ≥ 2: DVT likely
  • OCP, pregnancy, HRT

[Wells PS. NEJM 2003;349:1227-35]

slide6

fibrin

D

D

D

D

D

D

D-Dimer

fibrinolytic system

slide7

D-dimer

pos

neg

no test, no anticoag.

imaging test

Clinical Suspicion for DVT

unlikely

likely

[Wells PS. NEJM 2003;349:1227-35]

slide8

Clinical characteristics (Well’s criteria):

  • Active cancer
  • Paralysis or plaster immobilization
  • Bedridden ≥ 3 d; major surgery in 3 mo
  • Entire leg swollen
  • Calf swelling > 3cm
  • Pitting edema in affected leg
  • Collateral non-varicose superficial veins
  • Localized tenderness along deep veins
  • Previous DVT
  • Alternative dx more likely

1

1

1

1

1

1

1

1

1

-2

Case – Physical Examination

L > R by 2.5 cm

  • score < 2: DVT unlikely
  • score ≥ 2: DVT likely
slide9

D-dimer

pos

neg

no test, no anticoag.

imaging test

Clinical Suspicion for DVT

unlikely

likely

[Wells PS. NEJM 2003;349:1227-35]

slide10

Clinical characteristics (Well’s criteria):

  • Active cancer
  • Paralysis or plaster immobilization
  • Bedridden ≥ 3 d; major surgery in 3 mo
  • Entire leg swollen
  • Calf swelling > 3cm
  • Pitting edema in affected leg
  • Collateral non-varicose superficial veins
  • Localized tenderness along deep veins
  • Previous DVT
  • Alternative dx more likely

1

1

1

1

1

1

1

1

1

-2

Case – Physical Examination

  • score < 2: DVT unlikely
  • score ≥ 2: DVT likely
slide11

D-dimer

pos

neg

no test, no anticoag.

imaging test

Clinical Suspicion for DVT

unlikely

likely

[Wells PS. NEJM 2003;349:1227-35]

slide12

DVT Diagnosis

  • Doppler ultrasound
  • CT venogram
  • MR venogram
  • Contrast venography
slide13

D-Dimer Caveats

  • Know which test your lab uses
  • Neg. D-Dimer does not r/o distal DVT
slide14

Pre-test Probability - PE

  • Pre-test probability for PE:
  • Active cancer
  • Bedridden ≥ 3d or major surgery past 4 wks
  • Previous DVT/PE
  • Hemoptysis
  • Heart rate > 100/min
  • PE is most likely dx
  • Clinical signs + symptoms c/w DVT

1

1.5

1.5

1

1.5

3

3

  • score ≤ 4: PE unlikely
  • score 4-6: moderate probability
  • > 6 high probability

[Kearon, C. Ann Intern Med 2006;144:812-821]

[Wells PS. Thromb Haemost. 2000;83:416-20]

slide15

D-dimer

pos

neg

no test, no anticoag.

imaging test

Clinical Suspicion for PE

low

moderate or high

[Kearon, C. Ann Intern Med 2006;144:812-821]

[Wells PS. Thromb Haemost. 2000;83:416-20]

slide16

PE Diagnosis

  • Spiral (helical; PE-protocol) CT
  • VQ scan
slide17

Treatment – Thrombolytics

  • Does thrombolytic Rx ↓ development of PTS?
  • Not appropriately studied.

ACCP guidelines for DVT:

  • Recommend against routine use [1A]
  • Confined to selected patients (limb salvage) [2C]

[ACCP guidelines. Büller H et al. Chest 2004;126:401S-428S]

slide18

Thrombolytics in DVT

My approach/indications:

  • Massive DVT (phlegmasia coerulea dolens)
  • Young patient with extensive DVT
  • Cancer patient – quality of life, short-term
  • Individual discussion
  • Catheter-directed, tPA 0.5 mg/h (1-2 ports) for 24 hr or longer
slide19

Thrombolytics in PE

  • Give in life-threatening PE
  • Consider in “submassive” PE (pulm. HTN or right ventricular dysfunction

[NEJM 2002;347:1143-50]

[NEJM 2002;347:1131-32]

slide20

Treatment – Distal DVT

  • Proximal = popliteal vein and above
  • 1st DVT with transient risk factor: Symptomatic calf vein DVT: Rx same as prox DVT
  • Spontaneous distal DVT: no comments

[ACCP guidelines. Büller H et al. Chest 2004;126:401S-428S; page 410S]

slide21

Treatment – 1st Few Days

  • LMWH
  • Fondaparinux
  • Unfractionated heparin

[Büller HR. NEJM 2003;349:1695-702]

[Büller HR. Ann Intern Med 2004;140:867-873]

  • Overlap for at least 5 days
slide22

Treatment – Outpatient?

Outpatient Rx:

  • Effective
  • Safe
  • Feasable
  • Cost saving

ACCP on Acute DVT and PE:

  • LMWH qd or q 12 hr preferred over UFH (DVT/PE)
  • Outpatient if possible (DVT)

[Büller H et al. Chest 2004;126:401S-428S]

Admission:

  • significant DVT
  • “free-floating thrombus”
  • significant PE
slide23

Treatment – Outpatient?

  • Think twice!
  • Can patient afford cost of LMWH?
  • S.c. injection teaching
  • Access to INR-determination (anticoagulation clinic)
  • Warfarin dosing (nomogram)
  • Warfarin teaching
  • Elastic bandages/stockings – prescription

Outpatient Rx

  • LMWH q 12 hr or q d
  • Fondaparinux q d
  • S.c. heparin, fixed-dose

[NEJM 2006]

slide24

= TED

Postthrombotic Syndrome

Compression stockings

  • Grade 2, graduated (35 mm Hg at ankle, 25 at mid-calf, 18 at thigh)
  • individually fitted
  • below knee / above knee
  • as long as there is leg swelling
slide26

Case – Thrombophilia w/u

  • Thrombophilia w/u:
  • FVLeiden
  • II 20210 mutation
  • ATIII activity
  • Protein C activity
  • Protein S test
  • Homocysteine
  • Anticardiolipin antibodies
  • Lupus anticoagulant
  • Anti-β2-glycoportein I antibodies
slide27

DVT Recurrence Rate

  • Low
  • Transient risk factor
  • Moderate
  • No abnormality detected
  • hetero factor V Leiden
  • hetero II 20210

Spontaneous VTE

  • Higher
  • APLA
  • AT III
  • hetero FVLeiden plus II 20210
  • homo factor V Leiden?
slide28

DVT Recurrence Rate

[NEJM 2004;350:2558-63]

slide29

DVT Recurrence Rate

  • D-dimer pos
  • Residual clot
  • Elevated factor VIII
  • Elevated factor IX
  • Elevated factor XI
  • Men > women

D-dimer (on anticoagulants)

VIII

[Thromb Haemost 2002;88:162-3]

[NEJM 2000;343:457-62]

[Blood 2003;102:abstract 1133]

[NEJM 2004;350:2558-63]

[Br J Haematol 2004;124:504-10]

D-dimer (off anticoagulants)

[Thromb Haemost 2002;87:7-12]

[Blood 2004;103:3773-6]

[JTH 2006;4:1208-14]

Residual clot

IX

[Blood 2004;103:3773-6]

XI

[Blood 2004;103:3773-6]

slide30

Obtain:

D-dimer

Doppler legs

Lowest risk:

woman; DVT;

neg. D-dimer; no residual clot; was on OCP

Stop warfarin

INR 2.0- 3.0

  • Stable INRs?
  • Bleeding
  • Lifestyle changes?
  • Patient preference

Highest risk:

man, PE; pos. D-dimer; + residual clot

Length of warfarin Rx

My own approach

Acute

DVT/PE

6 mo

slide31

Low-dose warfarin?

  • Full-intensity warfarin (INR 2-3) is more effective than low-intensity (INR 1.5-2.0)
  • Low-intensity is also effective
  • Bleeding with full-intensity warfarin is similar to low-intensity
  • When choosing long-term warfarin, choose full-intensity.

[PREVENT trial: NEJM 2003;348:1425-34]

[ELATE trial: NEJM 2003;349:631-639]

slide32

Case – @ 6 months

  • Significant chronic left leg swelling + pain
  • D-dimer negative
  • Doppler Ultrasound: - “Leg: no residual clot”- “Suggestion of obstruction prox. to inguinal ligament”.
  • You think she may have……?

May Thurner syndrome

  • You order…..?

Pelvic CT or MR venogram

slide34

Postthrombotic Syndrome

  • www.biocompression.com
  • www.lympha-press.com
slide35

Thrombosis risk

Birth Control Options

  • Estrogen combination pill
  • 3rd generation
  • 2nd generation

???

Yasmin®

Ortho Evra®

  • Progestin-only
  • Depot Provera®
  • Minipill
  • Mirena IUD ®

Non-hormonal methods

www.fvleiden.org

slide36

For Health Care Providers

www.nattinfo.org

NATT

slide37

The Top 6 Questions I Get Asked

1. “What birth control options are there for women with h/o thrombosis or thrombophilia?”

2. “For the woman on warfarin, is it o.k. to take birth control pills?”

3. “What can the postmenopausal woman with h/o thrombosis or thrombophilia take for vaginal dryness?”

4. “What can be done about warfarin-associated fatigue?”

5. “What can be done about warfarin-associated hairloss?”

6. “What can be done about widely fluctuating INRs?”

slide38

Summary

  • High / low likelihood of DVT/PE (Well’s criteria)
  • D-dimer if low likelihood of DVT/PE
  • Thrombolytics: occasionally
  • Outpatient Rx: yes, but assess feasability
  • Thrombophilia w/u
  • Length of warfarin (thrombophilias, ♂ > ♀; D-dimer; lifestyle)
  • Compression stockings (grade 2); stents; pumps
  • www.nattinfo.org
  • DVT Prophylaxis