1. PE and DVT

2. Pathogenesis of VT Virchow’s triad: Damage to vessel wall
Venous stasis
Hypercoagulability

3. Source
Most PE’s originate from thrombi in the deep venous system of the legs, although they may also originate in the pelvic, renal or upper extremity veins.
HOWEVER, less than 30% of pts will have symptoms in their legs at the time of diagnosis of PE
20% of calf vein thrombi propagate above the popliteal fossa.
20% of lower extremity venous emboli begin in the proximal veins without prior calf involvement.

4. Acquired Risk Factors Age Previous thrombosis Immobilization
Major surgery – especially Ortho
Estrogen – OCP, HRT, SERMs
Antiphospholipid Ab syndrome
Malignancy
Nephrotic syndrome
Inflammatory bowel disease
Myeloproliferative d/o – esp p. vera and ET
PNH
Long distance air travel
HIT

5. Inherited Risk Factors
Factor V Leiden mutation
G20210A prothrombin gene mutation
Antithrombin deficiency
Protein C or S deficiency
Dysfibrinogenemia
Hyperhomocysteinemia

6. Presentation Dyspnea Pleuritic chest pain Cough +/- hemoptysis
On exam may have
Tachypnea
Tachycardia S4
Loud P2
May have fever – rarely >102
In massive PE can have hypotension and shock
Look at legs for swelling and Homan’s sign – but only helpful if positive.

7. Homan’s Sign
Passive dorsiflexion of the foot with the knee straight may give pain in the calf and back of the knee when there is a deep venous thrombosis.
Some concern that vigorous dorsiflexion of the foot can expel clot from the veins and so this test may have its dangers.
The sign is not specific for DVT

8. DDX swollen calf DVT Bakers Cyst Cellulitis
Gout – if really bad it can sometimes look like a cellulitis
If bilateral think about CHF, Nephrotic syndrome, liver failure, venous insufficiency, pregnancy or pelvic mass, vasodilators esp nifedipine

9. ABG Usually shows hypoxia, hypocapnia, respiratory alkalosis
A-a gradient:
Normal 7-14 depending on age
Increases with age, FiO2 and supine posture
Estimate of normal for age:
Age/4 +4
A-a gradient = (FiO2 x713 – pCO2/0.8) – PaO2
If A-a gradient normal, PaO2 <80, Pa CO2 >45 then hypoventilation accounts for hypoxia
Increased A-a gradient occurs in V/Q mismatch, shunting and any kind of barrier to diffusion (e.g. pulmonary edema)
BUT can be normal and still have PE!

10. Labs Troponin, LDH, AST and BNP may all be elevated
Check baseline CBC, PT/PTT/INR, Cr
D-dimer
Normal D-dimer excludes PE, but positive D-Dimer is not helpful (as it can be positive in many conditions including sepsis, immobility, post Sx and CAP)

13. EKG May have non specific ST and T wave changes
“Typical” SI, QIII, TIII - rare.
Sinus tachycardia
T wave inversions in right to mid chest leads
Poor R wave progression (acute RV dilation)
P pulmonale
RV conduction delays
Right axis shift

14. CXR May have area of atelectasis
May have wedge shaped infarct peripherally
Pleural effusion occurs in about 40%

15. DVT – D-Dimer Fibrin degradation product elevated in active thrombosis
Negative test can help exclude VTE
Preferred test
Quantitative Rapid ELISA – sensitivity 96/95% for DVT/PE
Other methods include latex agglutination and RBC agglutination (SimpliRED)
Less helpful in malignancy and recent surgery.
Rapid RBC agglutination (SimpliRED) – sensitivity 87/78% for DVT/PE
1st generation ELISA accurate but slow
Latex agglutination only useful if quantitative
Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Int Med. 2004;140(8):

16. DVT – D-Dimer
In 283 patients with suspected DVT, low-moderate Wells DVT score and negative d-dimer only 1 (NPV 99.6%) had DVT over next 3 months
556 consecutive patients with suspected DVT, 283 (51%) had low-mod prob and neg d-dimer
Used a quantitative latex agglutination test (sens 97.1% in this study; method sens 85%/89% for DVT/PE in Stien SR)
Sensitive d-dimer testing can rule out DVT in low-moderate risk patients
Bates SM, Kearon C, Crowther M, et al. Ann Intern Med. 2003;138:787-94

17. Doppler US of lower extremities
If high clinical suspicion should be repeated 7-10 days after initial scan as below knee DVT can propagate
Also remember that some pt develop DVT’s elsewhere – so you may not find a DVT in their legs if the source was their arm!

18. PE – Assigning Pretest Probability
Single most important step in the diagnosis of pulmonary embolism
May be done based on clinical judgment or aided by a clinical scoring system
Modified Wells Criteria is the most widely used and studied
Reliably stratifies patients by likelihood of PE to allow selection of safe (<2% VTE risk if no anticoagulation) management strategy
Low(57%) 1.3%; Moderate(36%) 16.2% and High(7%) 37.5%

19. DVT – Wells Score
The following were assigned a point value of 1 if present:
Cancer
Paralysis or plaster immobilization
Bedrest > 3d or surgery in past 4 wks
Localized tenderness
Entire leg swollen
Calf > 3cm larger than unaffected leg
Pitting edema greater than unaffected leg
Collateral superficial veins
Alternative diagnosis more likely than DVT = - 2 points
Probability High (≥ 3), Moderate (1-2) or Low (0 or less)
DVT risk: High – 75%, Moderate – 17%, Low – 3%
Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:1795-8

20. PE – Imaging Studies
PIOPED study quantified the value of V/Q scans in diagnosing PE
Normal/near-normal scans exclude PE in low-moderate risk patients
High probability scans confirm PE in moderate-high risk patients
Drawbacks: more difficult test and 73% patients had indeterminate scans
LE compression US showing DVT helps diagnostically, but a negative study insufficient to exclude VTE
PIOPED Study. JAMA. 1990;263(20):

21. Clinical Models to Assess PE Risk
PIOPED Criteria – Correlates well with incidence of PE
Based entirely of clinician impression, not clinical risk factors
Pretest Clinical Gestalt of PE Probability
Actual PE Rate on PA Angiogram
Low (“<20%” should have PE) 9%
Intermediate (“20-79%” should have PE)
30%
High (“80-100%” should have PE)
68%
PIOPED Investigators. JAMA 1990; 263:

22. PE – Helical CT (CTA)
Eng performed a systematic review (SR) of all studies & SRs on CTA prior to 2003
Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive for PE
In a similar SR in 2005 Roy concluded
Negative CTA could safely exclude PE in low risk patients
Negative LE US plus negative CTA could exclude PE in moderate risk patients
At the time of those SRs no studies of faster multidetector CTA (MDCT) were available
Faster scanning times and 50% thinner cuts presumably would result in increased sensitivity for smaller PEs
Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6): Roy PM, Colombet I, Durieux P, et al. BMJ 2005;331(7511):259.

23. PE – PIOPED II Published June 2006 in NEJM Findings
1090 consecutive patients with suspected PE
All given Modified Wells Score
MDCT - mostly 4 slice
Gold standard – composite - V/Q, angiogram & LE US
Findings
MDCT: sens 83% & spec 96% for PE
Positive predictive value >90% in moderate/high risk
Negative predictive value 96% in low risk patients but only 89% in moderate risk patients
Findings generally consistent with Roy’s SR
Concordant findings helpful -
Need neg LE US to exclude in moderate risk patients
Discordant findings – low pretest – pos CT or high pretest – neg CT need more testing.

25. V/Q scanning Look for evidence of ventilation perfusion mismatch
Can only really be done if pt has normal CXR
Normal scan virtually excludes PE even if pretest clinical probability was felt to be high.
If a patient with intermediate clinical probability of PE has an intermediate scan then need further testing

26. A 60-year-old man with asthma is evaluated in the emergency department because of the acute onset of chest pain while lifting a heavy object. The pain is sharp and accentuated by deep breathing and by movement of the upper extremities. It is located over the left precordium.
The physical examination and chest x-ray are normal. A ventilation-perfusion lung scan shows matched areas of perfusion and ventilation.
Which one of the following is the correct interpretation of the ventilation-perfusion lung scan?
( A ) Normal ( B ) Low probability ( C ) Indeterminate ( D ) High probability

27. Correct Answer = A
The lung scan is normal, with matched perfusion and ventilation. This lung scan rules out a pulmonary embolism, and another source for the chest pain should be sought. Often asthma does complicate the interpretation of the lung scan, but the problem relates to matched defects in which the airway obstruction decreases the ventilation to an area of the lung. The consequent hypoxia in that area leads to reduction in blood flow in the same area. These areas are rarely segmental.

28. Spiral CT/CT angiogram
Used if CXR not normal
Picks up large central emboli but is less sensitive for the smaller peripheral emboli.
True pulmonary angiography rarely used now, though can do direct thrombolysis in massive PE.

30. Echo
More than 80% of pts with PE will have abnormalities of RV size or function, or TR.
McConnells sign – regional wall motion abnormalities that spare the R ventricular apex are very suggestive of PE
BUT echo is only really used for Dx of massive lifethreatening PE’s when rapid diagnosis is needed to determine whether thrombolysis should be given.

31. Treatment
Identify any contraindications to anticoagulations – if yes then IVC filter
Inquire about h/o HIT
If yes, then use direct thrombin inhibitor
Assess need for hospitalization
Extensive iliofemoral DVT with circ compromise
Increased risk of bleeding
Limited cardioresp reserve
Poor compliance
CI to LMW heparin

32. Treatment Administer LMW heparin or unfractionated heparin
Goal x PTT in first 24 hours
Check platelet count on day 3-5
Treat at least five days and until patient’s INR is >2 on coumadin for two consecutive days
Start coumadin on day 1

33. Treatment Duration 3-6 months in most patients Indefinite treatment:
>1 spontaneous event
One spontaneous life threatening event
Antiphospholipid syndrome
Antithrombin deficiency
>1 genetic allelic abnormality
Homozygote for Factor V Leiden or prothrombin gene mutation
Heterozygote for both
Protein C/S deficiency
Continuing RF especially active advanced CA

34. Contraindications to Anticoagulation
Absolute
Active bleeding
Severe bleeding diathesis
Platelet count <20
Neurosurgery, ocular surgery or intracranial bleeding within the past 10 days

35. Contraindications to Anticoagulation
Relative
Mild/moderate bleeding diathesis or thrombocytopenia
Brain mets
Major abdominal surgery within 2 days
GI or GU bleeding within 14 days
Endocarditis
Severe HTN (SBP >200, DBP > 120)

36. Inferior Vena Cava Filter
Reduce risk of PE but carry increased risk of DVT
Use in pts with DVT who cannot take anticoagulation e.g. due to bleeding risk
Also used with or without anticoagulation in patients with high risk of death should further PE occur.

37. Hypercoagulation Workup
Test all patients for unprovoked VT for antiphospholipid ab syndrome and hyperhomocysteinemia

38. Hypercoagulation Workup
Test for Factor V Leiden, prothrombin gene mutation and deficiencies of antithrombin, protein C/S in the following patients:
Family h/o VT
VT before the age of 50
Recurrent VT
Thrombosis in an unusual site (mesenteric, renal, cerebral, hepatic)
Heparin resistance (antithrombin deficiency)
Warfarin induced skin necrosis (protein C/S def)
Neonatal purpura fulminans

39. Hypercoagulation Workup
Wait to check for deficiency in antithrombin, protein C or S until 2 weeks after anticoagulation rx is completed

40. VTE – Prevention Underutilized
DVT-FREE prospective registry of 5,451 patients at 183 US hospitals
Only 32% of medical patients with DVT received DVT prophylaxis

41. VTE – Prophylaxis in Medical Patients
Indications
CHF or severe respiratory disease
Bedrest with additional risk factor
Cancer
Prior VTE
Most ICU patients
Options
Low dose unfractionated heparin or LMWH
Sequential compression devices
Graduated compression stockings
Acute neurologic disease
Inflammatory bowel disease