This document provides a historical overview of the diagnosis and treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). It discusses key discoveries and studies that advanced the understanding and management of these conditions, such as Virchow identifying PE in 1846, studies in the 1960s establishing the use of heparin to prevent DVT and fatal PE after surgery, and randomized controlled trials in the 1990s comparing heparin/warfarin to heparin/warfarin plus inferior vena cava filters for DVT treatment. The document also reviews current diagnostic methods and medical and interventional treatment options for DVT and PE.

1. Diagnosis and Treatment
of Deep Venous
Thrombosis and
Pulmonary Embolism
Beth Stuebing, MD, MPH

2. History
 Susruta (Ayurveda physician
and surgeon, 600-1000 B.C.) –
patient with a “swollen and
painful leg that was difficult to
treat”
 Giovanni Battista Morgagni,
1761 – recognized clots in
pulmonary arteries after
sudden death, but didn’t make
the connection to DVT

3. Virchow Strikes Again
 “Discovered” PE in 1846 –
“the detachment of larger
or smaller fragments from
the end of a softening
thrombus which are carried
along the current of blood
and driven into remote
vessels. This gives rise to
the very frequent process
on which I have bestowed
the name Embolia”

4. Deep Venous Thrombosis
- Epidemiology
 1969 paper by Kakker
– 30% of post-op patients develop clot in calf
veins
– 35% of these lysed within 72 hrs
– 15% of pts with persistent thrombosis developed
PE
 Recent studies put incidence at 50 per
100,000 person years
 Incidence greatly increases with age, 18%
of 80yr old patients have asymptomatic DVT

5. DVT Diagnosis
 Wells clinical prediction rules
 D dimer ELISA assay >90% sensitive, but 40-
50% specific
 When D dimer is negative and clinical
suspicion low, further studies are
unwarranted
 Ultrasound most sensitive and specific
(>90%) for symptomatic, proximal vein
 US only 50-70% sensitive for asymptomatic
pts
 Sens. And spec. much lower for symptomatic
arm DVT (60-90%)

6. DVT Treatment (medicine)
 Initial treatment with UFH or LMWH
 Goal aptt (with heparin) 1.5-2.5x nl
 25% pts resistant to heparin, better to monitor anti-factor Xa instead
 LMWH monitoring not necessary, but can be done with goal anti Xa
level 0.6-1 U/ml (drawn 4hr after dose)
 Age increases bleeding risk
 Some studies suggest lower mortality with LMWH in elderly
 Transition to warfarin (goal INR 2-3), or continue with LMWH
 Starting with large doses (10mg) NOT recommended
 3 months treatment with temporary, known risk factor (fracture,
pregnancy, air travel)
 At least 6 months treatment with no discernible cause
 Hypercoagulable workups not necessary in the elderly
 Length of treatment a risk:benefit analysis
 Major bleeding risk 1-3% per year with INR 2-3

7. DVT Treatment - Filters
 Consider in pts with contraindications to
anticoagulation or develop recurrent DVT or
PE despite adequate medical therapy
 Randomized trial of anticoagulation +/-
IVCF:
– PE at day 12 reduced with filter, but benefit
didn’t persist
– Double risk of recurrent DVT with IVCF

8. Pulmonary Embolism -
Epidemiology
 1/3 of people with DVT may develop
symptomatic PE
 1975 paper
– Incidence 630,000 per year
– Death within 1 hour in 11%
– Undiagnosed 1 hr survivors: eventual 30%
mortality
– Diagnosed 1 hr survivors (treated): 8% mortality

9. PE Diagnosis
 Clinical diagnosis is nonsensitive and
nonspecific
 ECG
 ABG
 CXR
 Angiogram
 VQ scan
 ECHO
 CT chest

10. ECG Changes
 “S1 Q3 T3”
 S wave in lead I
 Q wave in lead III
 Flipped T in lead III
 Possible RBBB
 Signs of cor pulmonale
 Classic, but uncommon

11. Arterial Blood Gas
 Hyperventilation leads to low pCO2
 Difficulty in oxygenation
 Alveolar-arterial gradient may be
elevated (80% of cases)
 A-a O2 Gradient = [ (FiO2) *
(Atmospheric Pressure - H2O
Pressure) - (PaCO2/0.8) ] -
PaO2 from ABG
Nl Gradient Estimate = (Age/4) + 4

12. CXR – even post mortem!
 Westermark sign - ischemia appeared as a clarified
area with diminished vascularity corresponding to
the extent of the embolized artery

13. Pulmonary Angiography
 Started in 1950s
 47% positive
studies had no
signs on CXR
 1st confirmatory test
other than autopsy

14. VQ scan
 Started in 1960s
 Correlated well with
angiogram and
autopsy
 “High probability”
scans: 41% sensitive,
97% specific
 Adequate for diagnosis
in a minority of
patients

15. ECHO for PE
 RV dilates and LV is smaller in most
patients
 Unreliable in pts with prior cardiac
dysfunction
 TEE reported to be >90% sensitive
and specific
 Right heart dysfunction resolves after
thrombolytic therapy

16. CT Chest
 Spiral CT chest
introduced in early
1990s
 Sensitivity 86-
100%, specificity
92-96% for central
PE
 63% sensitive for
subsegmental PE

17. PE Treatment
 Heparin
 Embolectomy
 Thrombolytics
 Venous interruption
 IVC filter

18. Heparin - Warfarin
 Not used until 1940s
 Only prospective randomized trial in
1960s
– 2 weeks of anticoagulation after PE
– No deaths or nonfatal PE in treatment
group
 1990s - LMWH found equally effective

19. Trendelenburg’s Procedure
 Thromboembolectomy,
described in 1908
 First survivor of the
procedure not until 1924
 Via left chest
thoracotomy

20. Thrombolytics
 Introduced in 1960s
 Unclear benefit over heparin,
significant bleeding risk
 Now used for massive PE with
hemodynamic deterioration
 Can be direct or systemic
 2-3% risk intracranial hemorrhage

21. Venous Interruption
 Started with femoral vein ligation in
1930s
 1940s, Homan suggested IVC ligation
instead
 Led to the first IVC nonextractable
filter in 1969

22. IVC Filters
 Decousus, et.al., 1998
randomized trial for DVT:
heparin/warfarin alone
versus heparin/warfarin
plus IVCF
– No difference in 2 year
mortality
– Less PE but more recurrent
DVT in filter group

23. Prevention
 1960s study: heparin q12h for 7 days
after major surgery decreased DVT
from 42% to 8%
 Established as standard of care after
1975 study with similar results
 60-70% relative risk reduction for DVT
and fatal PE post-op

24. DVT and PE in the ICU
 One study: routine Doppler shows DVT in up
to 30-40% of all ICU patients, regardless of
prophylaxis
 Much less likely to have physical exam
findings
 One study showed 38% of ICU pts with
known DVT had undiagnosed PE on VQ scan
 One autopsy study: 84% of PE were not
diagnosed antemortem

25. DVT and PE in the ICU
 Chemical prevention has similar risk
reduction of 60-70%, variety of meds
studied
 CT chest is higher risk (contrast load, travel
with critical patient) and often unfeasible
 VQ scans essentially uninterpretable given
multitude of pulmonary pathology
 Higher risk: personal or family history, renal
failure, platelet transfusion, vasopressor
use, longer time on ventilator

26. Thanks, and Questions?