Venothromboembolism

1. Venous Thromboembolism
Dr. Nasib Al shibli
Surgical Specialist
MRCS (Ireland)
Arab Board (ABHS.GS)
Syrian Board (G.S)
10..Dec.2016 1

2. Venous Thromboembolism
• Two major clinical manifestations
– deep venous thrombosis (DVT)
– pulmonary embolism (PE)
– 30% DVT pts develop symptomatic PE
50%-60% DVT pts develop asymptomatic PE
• VTE affects 1/1000 persons yearly
• PE causes 50,000 death in the U.S. yearly
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3. DVT - Risk factors and Prevalence
DVT most often originates in the deep
veins of the major calf muscles
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• venous stasis
• trauma
• surgery
• childbirth
• increasing age
• all cancers

4. Thrombophilia
Definition
recurrent venous or arterial thrombosis
from inherited or acquired causes
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5. Inherited Thrombophilic States
Prevalence (%)
Patients with VTE
1st
Event
Activated protein C resistance 3-4 20 50 3-7
Hyperhomocysteinemia - 15 - -
Protein C deficiency 0.2-0.4 3 1-9 5-12
Protein S deficiency 0.1 2 1-13 4-11
Antithrombin deficiency 0.02 1 0.5-7 15-20
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General
Population Recurrence RR*
* Relative Risk for recurrent VTE. Relative to an index case no inherited thrombophillia.
Am J Respir Crit Care Med. Vol 159: 1-14; 1999

6. Activated Protein C Resistance
• Inheritated abnormality known as factor V Leiden
• involves a point mutation (adenine for guanine) that
results in the substitution of glutamine for arginine at
position 506 on factor V
• activated protein-C becomes resistant to degradation
• the heterozygous state (5% of Caucasians) carries a 3 to
5 fold increased risk for VTE
• Factor V Leiden can be identified in 20% of patients with
one episode and 50% of those with recurrent VTE
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7. Prevention of Venous Thromboembolism
Without Prophylaxis (%) Recommended With Prophylaxis (%)
Risk Group Prox DVT Fatal PE Prophylaxis Prox DVT Fatal PE
Hip replacement 20-30 2-4 WAR, LMWH 5 0.1-0.2
Knee replacement 20-30 2-4 WAR, LMWH, IPC 5 0.1-0.2
Hip fracture 25-35 2-4 WAR, LMWH 10 0.2-0.4
Major trauma 20 0.5-1.0 LMWH, IPC 10 <0.1
Abdominal or pelvic
cancer surgery 20 0.5-1.0 LMWH, IPC, WAR 10 <0.1
Abdominal surgery,
coronary artery 5-7 0.5 UF, LMWH, IPC <1 <0.1
bypass graft WAR, ES
Medical patients
>40, immobilized 5 <0.5 UF, ES, LMWH <1 <0.1
10..Dec.2016 Am J Respir Crit Care Med. Vol 159: 1-14; 1999
ES = elastic stockings; IPC = intermittent pneumatic compression; UF = unfractionated heparin

8. Prevention
• Anticoagulation and other antithrombotics form the
basis for prophylaxis
• Drugs are continued for 5-7 d for high-risk; 7-10 d
for orthopedic procedure on the lower extremity
• No prophylactic technique is completely effective
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9. Vena Caval Filters
prophylactic device for pulmonary embolism
• patient with proximal DVT
– who cannot receive anticoagulants
– who has failed anticoagulants
• patient undergoing pulmonary embolectomy
• patient undergoing pulmonary endarterectomy for
chronic thromboembolic pulmonary hypertension
• filters appear to prevent PE within the following 2
wks but did not affect short or long-term mortality
10..Dec.2016

10. Diagnosis
• Of patients with suspected DVT, only one in four will
prove to have DVT
• Differential diagnosis:
– cellulitis, heart failure with edema, ruptured Baker’s cyst,
chronic venous insufficiency
• Diagnostic tests:
– ultrasound with manual compression
– contrast venography
– fibrin degradation product D-dimer
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11. Diagnostic Approach to DVT
S U S P E C T D V T ?
S t i l l s u s p i c i o u s ?
R e p e a t U / S i n 2 - 3 d
W i h t h o l d t r e a t m e n t
- U / S
l o w c l i n i c a l s u s p e c i o n
C o n t i n u e h e p a r i n I V ,
s t a r t w a r f a r i n
+ U /S
f o r p r o x i m a l D V T
C o n t r a s t v e n o g r a m
U / S
e q u i v o c a l
G i v e h e p a r i n a n d o r d e r U l t r a s o u n d
10..Dec.2016 11Am J Respir Crit Care Med. Vol 159: 1-14; 1999

14. Natural History of DVT
• Untreated proximal DVT
– clinical PE occurs in 1/3 to 1/2 of patients
– sub-clinical PE occurs in another 1/3
– untreated PE tends to recur in days to weeks
• Post-phlebitic syndrome (10-30% of DVT)
– pain, edema, skin discoloration, and ulceration
associated with chronic venous insufficiency
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15. Pulmonary Embolism
Three major clinical presentations:
1. dyspnea with or without pleuritic chest pain and
hemoptysis
2. hemodynamic instability and syncope (usually
associated with massive pulmonary embolism)
3. mimicking indolent pneumonia or heart failure,
especially in the elderly
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16. Common symptoms of Acute PE
• PIOPED study found
– Dyspnea
– Pleuritic chest pain
– Tachypnea (resp rate ≥ 20 / min)
in 97% of patients with angiographic proven PE
• The absence of this triad reduces the clinical
probability of PE
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17. Estimating Clinical Probability of
Pulmonary Embolism
High Risk factor present
(80-100% probable) Otherwise unexplained dyspnea, tachypnea, or pleuritic
chest pain
Otherwise unexplained radiographic or gas exchange
abnormality
Intermediate Neither high nor low clinical probability
(20-79% probable)
Low Risk factor not present
(1-19% probable) Dyspnea, tachypnea, or pleuritic pain possibly present
but unexplained by another condition
Radiographic or gas exchange abnormality possibly
present but explainable by another condition
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Am J Respir Crit Care Med. Vol 159: 1-14; 1999

18. Diagnostic Test
• Ventilation-perfusion lung scan
≥ 2 moderate-to-large perfusion defects (>25% of a lung segment)
with intact ventilation in a clear chest x-ray in the involved area
• Widened (A-a) O2 gradient
– low PO2, low PCO2
• Chest x-ray
– central pulmonary artery engorgement, paucity of peripheral vessels
(Westermark sign)
• Electrocardiogram
– nonspecific ST-T changes, right-axis, S1-Q3-T3, P-pulmonale
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19. Suspect Pulmonary Embolism ?
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Give heparin IV and order V/Q scan
Low V/Q probability,
low clinical probability
High V/Q probability +
high clinical probability
Intermediate V/Q probability,
Low or high V/Q prob with
discordant clinical probability
Probability
V/Q Clinical
1. Low Mid
2. Mid Low
No treatment
Probability
V/Q Clinical
3. Low High
4. Mid Mid / High
5. High Low / Mid
Leg Ultrasound Treat
_
Pulmonary
Angiography
+
+
Am J Respir Crit Care Med. Vol 159: 1-14; 1999

20. CTPH
Chronic Thromboembolic Pulmonary Hypertension
• Result of recurrent or unresolved PE
• Occurs in 1% of patients with PE
• Sx: increasing dyspnea, exertion → constant
• Diagnosis:
– diagnosis should be considered in any one with
unexplained dyspnea on exercise
– V/Q scan shows multiple large defects
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21. Outcomes
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Close to 30% of patients who have an acute DVT develop the PTS by year
8 following their initial episode. Most develop signs and symptoms of this
condition within 2 years of their acute event, and nearly 25% develop a
chronic venous stasis ulcer.
Of the approximately 300, 000 Americans who have a fatal PE each year,
as many as 15% to 25% present with sudden death or die within 30 days
of their diagnosis.The majority of patients die because of a failure in
diagnosis rather than inadequate therapy.
In fact, the mortality rate for PE without treatment is approximately 30%,
whereas it is only 2 to 8% with adequate therapy. In addition, nearly 4% of
all PE patients develop CTPH by the second year following their event.

22. LMWH- Products and Doses:
Prophylaxis
•Dalteparin (Fragmin)- 5000 U SC
daily
•Tinzaparin (Innohep)- 3500 -4500 U
SC daily
•Enoxaparin (Clexane)- 30 mg BID –
40 mg daily SC

23. Low–Molecular-Weight Heparin (LMWH)
Advantages
 Efficacious
 Fixed dosing
— Once-daily dosing available
 Monitoring rarely required
 More easily used in long-term
outpatient use
 Risk of HIT<UFH
Disadvantages
 Subcutaneous (sc) injections may be
difficult for some patients (home care)
— Requires education
 Not fully reversible
 May be difficult to monitor in weight-
extreme individuals
 May be difficult to dose in patients
with renal insufficiency
 Cost issues

24. 24
Factor Xa Inhibitors
Fondaparinux is an indirect factor Xa inhibitor that can be used as VTE
prophylaxis in medical patients, those undergoing orthopedic procedures (total hip
and knee arthroplasty), and those undergoing abdominal surgery. It is also
approved as treatment for acute DVT and PE when used in combination with a
VKA. Its efficacy and safety in comparison to LMWH for the treatment of acute
DVT and in comparison with IV UFH for the treatment of PE has been shown in
large randomized, controlled trials.
Fondaparinux is administered as a once-daily subcutaneous injection of 2.5 mg for
DVT prophylaxis and 5 mg, 7.5 mg, or 10 mg based on body weight (<50 kg, 50-
100 kg, >100 kg, respectively) for the treatment of DVT or PE. Fondaparinux is
contraindicated in patients with severe renal impairment (creatinine clearance
<30 mL/min) and bacterial endocarditis

25. Warfarin
Advantages
 Efficacious
 Oral administration
 Appropriate for long-term
outpatient use
Disadvantages
 Requires frequent monitoring
and dose adjustments
 Slow to achieve full therapeutic effect
(~5 days)
 Numerous drug interactions
 Dietary precautions
 Inter/intrapatient variability

26. Intermittent Pneumatic Compression (IPC)
Advantages
 Effective for
DVT prophylaxis only
 No increased risk of hemorrhage
 May be combined with
pharmacologic agents
Disadvantages
 Not well studied
 Poor patient tolerability
— Poor compliance = poor efficacy
 Difficult for staff use
 Not convenient for outpatient
or long-term use
 Poor compliance

27. Graduated Elastic Compression Stockings (ECS)
Advantages
 Reduces distal DVT
 No increased risk of
hemmorhage
 May be combined with
pharmacologic agents
Disadvantages
 No data on proximal DVT, PE
 15% to 20% of patients cannot wear
them
 Appropriate for adjunctive therapy
only
 Poor compliance

28. Treatment
• iv heparin until the diagnosis is ruled out
• heparin - UFH or LMWH
• warfarin / coumarin derivatives
• adjunctive recommendations:
– bed rest until heparin is therapeutic
– elastic stockings until patient becomes
ambulatory (↓ post-thrombotic syndrome)
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29. Body Weight-Based Dosing
of Intravenous Heparin
• Initial dosing: Loading 80 U/kg → 18 U/kg/hg (APTT in 6 hrs)
APTT(s) Dose Change Additional Next APTT (h)
(x normal) (U/kg/h) Action
<35 (1.2 x) +4 Rebolus 80 U/kg 6
35-45 (1.2-1.5x) +2 Rebolus 40 U/kg 6
46-70 (1.5-2.3x) 0 0 6*
71-90 (2.3-3.0x) -2 0 6
>90 (<3x) -3 Stop infusion 1 h 6
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* During first 24 h, thereafter, once / day
Am J Respir Crit Care Med. Vol 159: 1-14; 1999

30. Low-Molecular-Weight Heparin
Drug Prophylactic Indication Treatment Dose
Ardeparin Knee arthroplasty 130 anti-Xa U/kg bid
(Normaiflo)
Dalteparin Abdominal surgery 120 anti-Xa U/kg bid
(Fragmin)
Enoxaparin Hip or knee arthroplasty, 1-1.5 mg/kg bid
(clexane) Abdominal surgery (1 mg ≈ 100 anti-Xa units)
Danaparoid Hip arthroplasty
(Orgaran)
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* LMWH < 5.6 kD, lose anti-IIa activity, cannot be reliably monitored with APTT
Am J Respir Crit Care Med. Vol 159: 1-14; 1999

31. Case No.1
• 28 yo man. MVA. Acute spinal cord injury
and multiple trauma victim.
– Risk of DVT
– what to do?

32. ASCI and Trauma
• Major trauma DVT rate is >50% (10-20%
proximal)
• 67-100% if acute SCI involved
• fatal PE up to 2%
• 3rd leading cause of death if pt survives
the first 24 hours

33. ASCI and Trauma
• RCT (trauma)
– UFH
• total DVT 44%, prox DVT 15%
– LMWH (enox 30 bid)
• total DVT 31%, prox DVT 6%
• RCT (ASCI subgroup)
– UFH
• total DVT 67%, prox DVT 13%
– LMWH (enox 30 bid)
•

34. ASCI and Trauma
• How long to Rx?
– The trauma studies used 14 days of Rx
– ASCI is different
• Chen et al. 1649 pts at 18 Rehab Units. 10%
developed DVT and 3% developed PE at Rehab
• Yelnik et al. 14% developed new DVT on venogram
within one month of starting rehab

35. ASCI and Trauma
• Bottom line:
– for trauma use LMWH
– studies used enoxaparin 30 bid for 14 days

36. Case No.2
• 62 yo man, post hemicolectomy for colon
CA. Previously well. No meds. No fam hx.
• What to do?

37. General Surgery Prophylaxis
• Pooled data for significant general
surgery suggests VTE rate is 19-25%
• 29% if pt has cancer
• most asympt below knee clots
• prox DVT 7%
• PE 1.6%
• fatal PE 0.9%

38. General Surgery Prophylaxis
• With UFH total DVT drops to 8%
• one meta-analysis suggests 5000 q8h
better than q12h
• little data compares UFH to LMWH
• likely equally effective
• maybe less bleeding with LMWH

39. General Surgery Prophylaxis
• What about extended Rx?
– NEJM March 28, 2002
– LMWH continued for 21 days after general
cancer surgery (compared to placebo at
home)
– all VTE 12% to 4.8%
– prox DVT 1.8% to 0.6%
– almost no symptomatic events occurred in
either group

40. Back to the case
• Basically for general surgery use LMWH
or UFH while immobile and while in
hospital
• Use q8h preferably
• if cancer related then consider extending
out Rx especially if very high risk and
ongoing immobility

41. CONCLUSIONS
• Use combo of clinical models, d-dimer,
and imaging to dx VTE
• be aggressive with DVT prophylaxis
– it is generally under-utilized

42. Thanks for your attentions !