Deep Vein Thrombosis
Brian M. Johnson, MD
CCRMC PBL
11/7/12
Case 1
Mrs. Z, a 44-year-old woman without significant
PMH, presents for an urgent visit with left leg
swelling of two days duration. She takes no
medications and reports moderate leg pain but
no chest pain, shortness of breath, or
palpitations.
What is the differential diagnosis of
unilateral leg swelling?
1. DVT
2. Cellulitis
3. Baker’s cyst
4. Lymphedema
5. Fracture
6. Post-thrombotic syndrome
7. Venous insufficiency
8. Scorpions? Or bee stings?
9. Toxins
10. Mass
11. Trauma / Compartment syndrome
What are risk factors for DVT?
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Hospitalization
Long-term immobility
OCP
Smoking
Age
Surgery
Cancer
CHF
Renal disease
Cirrhosis
Pregnancy
Anti-psychotics
Thrombophilias
Obesity
Restrictive clothing
Gender
Lupus (and other autoimmune diseases)
Sickle Cell
Case Continued…
• She reports that she has no family history of blood clots to
her knowledge and that she is not pregnant. She denies any
“warning signs” of cancer and is up to date on her cancer
screening (mammogram, Pap smear; no colorectal cancer
screening, but she denies family history of colorectal cancer
so she is not yet due). She denies recent immobilization or
trauma.
• Her exam is significant for a minimally swollen right calf. To
ensure a reliable assessment of circumference, you mark off
10cm below each tibial tuberosity and measure the
circumference at that level. You find that the right calf
measures 1cm larger in circumference than the left. There is
no edema or skin changes; no masses/cords are palpable.
The thighs are symmetric, and no superficial veins are noted.
How could you determine the
probability of the DVT in this patient?
What is the probability that this patient has a
DVT? Modified Wells
Clinical feature
Score*
Active cancer within 6 mo
1
Paralysis, paresis, or cast of lower
extremity
1
Recently bedridden >3 d or major surgery
within 4 wk
1
Localized tenderness along distribution of
deep vein system
1
Calf diameter >3 cm larger than opposite
leg†
1
Pitting edema
1
Collateral superficial veins (nonvaricose)
1
Alternative diagnosis as likely or greater
than that of DVT
-2
Clinical model for predicting pretest probability for DVT
*Interpretation: 0 = low probability = 3% frequency of DVT; 1-2 = medium
probability= 17% frequency of DVT; ≥3 = high probability = 75% frequency of DVT.
†Measured 10 cm below tibial tuberosity.
How would a d-dimer help?
Statistically
-Sensitive not Specific (useful if it’s negative)
-High false positive rate
Biomedically
- measures level of coagulation process in the
body
Case 2
Ms. W, comes with the exact same presenting complaint and
past medical history. The only difference in the presentation of
Ms. W. is that she does report that she had the “flu” about one
week ago and was in bed for four to five days.
Additionally, her exam is significant for a swollen and tender
right calf, measuring 4 cm wider in circumference than the left.
There is pitting edema on the right lower extremity, extending
to the inferior calf. There is no change in the skin, and no
masses/cords are palpable. The thighs are symmetric, and no
superficial veins are noted.
What’s the probability this patient has
a DVT?
75%!! High, with wells score greater than 3
What’s the value of doing a d-dimer?
• If high probability 21% still positive for DVT
even with negative D-dimer
What other test could you preform?
• Venous Doppler
• (venography)
13
Operating characteristics of
diagnostic tests for proximal DVT*
Black et al.
*
Diagnostic test
Sensitivity, %
Specificity, %
Positive LR
Negative LR
~100
~100
Infinity
0
Duplex
ultrasonography
95
95
19
0.05
Impedence
plethysmography
80
95
16
0.21
Iodine 125
fibrinogen scan
79
62
2.1
0.34
88-100
55-80
1.9-5.0
0.4-0.02
Venography
D-Dimer level
LR = likelihood ratio.
U/S negative. End of story?
• With high probability clinical exam but
NEGATIVE U/S:
– Consider other imaging, repeat study or obtain Ddimer.
– Consider treatment
U/S positive. Can she be treated as an
outpatient?
• Yes
– Need immediate anticoagulation (i.e. Lovenox) then
can bridge to warfarin
• No
–
–
–
–
–
–
Obesity
Cachetic
Renal failure (GFR <40)
High bleeding risk
Complicated medical history
Poor resources
For how long?
• Unprovoked 6 months?
• Provoked 6 months?
What’s a provoked DVT and why does
it matter?
• Risk factors
– Major: Cancer, Major Surgery, Major trauma
– Minor: Preg., long flight, OCP, smoking, minor
trauma, minor surgery
Risk of VTE recurrence after stopping
anticoagulation
Risk factor
1st year
Next 5 years
Distal DVT
3%
<10%
Major transient
3%
10%
Minor transient
5-6%
15%
Unprovoked
At least 10%
30%
Recurrent
>10%
>30%
Kearon, American Society Hematology Dec. 2004
Is longer anticoagulation better in
idiopathic DVT?
TRIAL
Duration
Recurrence
Duration
Recurrence
THRIVE
3mo
7.6/ 100pt yrs
2.1 yrs
2.6/100pt yrs
PREVENT
6mo
12.6%
18 mo
2.8%
Schulman et al. N Engl J Med 2003
Ridker et al. N Engl J Med. 2003
Do the experts agree with the
ACCP recommendations?
8th ACCP British
Recent recommendations
guideline Thoracic
Society
First VTE,
Provoked
3 months 4-6
weeks
First VTE,
Idiopathic
At least 3 3 months Indefinite
months,
evaluate
for
indefinite
tx
3 months if distal or upper
extremity; 6 if proximal DVT or
PE
Should I do the thrombophilia work
up?
Incidence of recurrent VTE
Christensen et al. JAMA 2005.
Patient group (total 474 pt)
Recurrence of VTE/year
With 1 thrombophilia
2.5%
Initial VTE provoked
1.8%
Initial VTE idiopathic
3.3%
Idiopathic with
thrombophilia
Idiopathic without
thrombophilia
Total group
3.4%
3.2%
2.6%
23
How can I determine who’s at risk for
recurrent clot?
•
•
•
•
•
•
•
24
Thrombophilia
Male gender
Active cancer (i.e. ongoing risk factors)
Recurrent dvt
Proximal over distal
Morbidity from DVT
Repeat studies (US and ddimer)
Algorithm for Determining Duration of
Treatment
After 3m CHECK U/S assess
bleeding risk (& discuss
indefinite tx if pt with PE,
Male or thrombophilia)
Female: No residual clot.
Clinical risk rule <1, stop
AC
Male: No residual clot,
stop AC, measure d-dimer
after 30d and stop if
normal.
Evidence of residual clot,
continue AC and repeat
U/S
REFERENCES
Bates SM, Kearon C, Crowther M, et al. A diagnostic strategy involving a quantitative latex D-dimer assay
reliably excludes deep venous thrombosis. Annals of Internal Medicine. 2003;138(10):787-794.
Black ER, Bordley DR, Tape TG, Panzer RJ. Diagnostic Strategies for Common Medical Problems. Philadelphia:
American College of Physicians; 1999.
Bruinstoop, E., Klok, F. A.,Van de Ree, M. A., Oosterwijk, F. L. and Huisman, M. V., Elevated d-dimer levels
predict recurrence in patients with idiopathic venous thromboembolism: a meta-analysis. Journal of
Thrombosis and Haemostasis, 2009;7: 611–618
Ofri D Diagnosis and treatment of deep vein thrombosis
West J Med. 2000 September; 173(3): 194–197.
Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM,
Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ, PREVENT
Investigators N Engl J Med. 2003;348(15):1425
Rodger et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can
discontinue anticoagulant therapy. CMAJ August 26, 2008 vol. 179 no. 5
Schulman S, Wåhlander K, Lundström T, Clason SB, Eriksson H. Secondary prevention of venous
thromboembolism with the oral direct thrombin inhibitor ximelagatran.. N Engl J Med 2003 Oct
30;349:1713-21