Lucid discussion on the risk factors, clinical presentation and prevention of deep venous thrombosis in surgical patients

1. DEEP VENOUS THROMBOSIS
DR ITAMAN, USIFOH
surgery registrar
Presented 0n 30/6/2019 to the Department of
Surgery, ISTH, as part of the requirements for the
Part 1 Post-graduate Training Programme in
Surgery

2. OUTLINE
• Introduction
• Relevant anatomy and physiology
• Epidemiology
• Risk factors
• Classification
• Pathogenesis
• Clinical features
• Diagnosis
• Prevention
• Treatment
• Complications
• Conclusion

3. INTRODUCTION
• Venous thromboembolism (VTE) is a spectrum of
clinical manifestations that includes deep venous
thrombosis (DVT) and pulmonary embolism (PE)
• Thrombosis is the formation of a clot (thrombus)
from blood constituents within the vessels of a
living body.
• When this phenomenon occurs in the deep veins,
it is called DVT
• Results from imbalance between the pro
coagulant and anticoagulant factors .

4. • Commonly occurs in the deep veins of the
lower limbs but can occur in the pelvic,
subclavian/axillary .
• It is a preventable cause of morbidity and
mortality .
• Clinical diagnosis is insufficient

5. HISTORICAL BACKGROUND:
• 1644, Schenk first observed venous thrombosis
• 1819, Laennec described PE
• 1846, Virchow recognized the association btw DVT in
the leg and PE
• 1877, first embolectomy by Trendelenburg
• 1937, Heparin was introduced
• 1948 Warfarin was synthesized by Karl Link
• 1976 First IVC filter (Mobin-Uddin) approved for use
• 2010 Rivarobaxan
• 2014 Dabigatran

6. RELEVANT ANATOMY

8. VASCULAR PHYSIOLOGY
Haemostasis:
 Keeps blood within the blood vessels
 Achieved by
 Vessel wall contraction
 Platelets adhesion & aggregation
 Coagulation activation

11. Anticoagulation process
 Prevents excessive coagulation
 Antithrombin III
 Thrombomodulin
 Protein C & S(inactivate factors Va and VIIIa)
Fibrinolysis
 Fibrinolysins
 Inactivate Va & VIIIa
 Lysis clot deposits
 Recanalization
• Equilibrium between these processes maintains blood in the fluid state
within the vessels

12. EPIDEMIOLOGY
Exact incidence is unknown;
• About 80 cases per 100,000 population annually
• In US, DVT accounts for 600,000
hospitalizaton/ yr
• M:F – 1.2:1
• Age >40yrs
• Less common in the pediatric population; about
1 in 100,000 people

13. EPIDEMIOLOGY cont’d
• Clinically recognised disease accounts for 1 in
20 deaths in patients above 50 years
• Autopsy shows that ≈ 80% DVT & PE are
undiagnosed
• Prevalence highest in
–Hospitalised patients
–Post operative and traumatized patients
–Severe co-existing illness

14. RISK FACTORS

16. IMMEDIATE PERIOP RISK FACTORS
• Nature and duration of operation
• The anaesthetic technique used
• The degree and duration of immobility
• Dehydration or sepsis
• Surgery
–70% after non-elective hip surgery
–48% after elective hip surgery
–12% after elective general surgery

17. CLASSIFICATION
1. Based on location
• Proximal
• Distal
Proximal versus distal (70%)
2. Based on etiology
• Primary (idiopathic)
• Secondary

18. PATHOGENESIS
 Activation of Clotting cascade in a vessel leads to thrombus formation.
• Virchow’s Triad – stasis
- hypercoagulability
- vascular endothelial injury
 Contrasting pathogenesis of Arterial & Venous thrombus
 Unlike with arterial thrombus where endothelial damage initiates the
clot, venous clots mostly occur without any endothelial injury.
 Low flow + Tissue factor !!

20. Diagnosis
• Risk assessment
• Clinical presentation
• Investigations

21. RISK ASSESSMENT
• Wells
• Rogers
• Caprini
• Padua
• VTE-BLEED score
• IMPROVE risk assessment model

22. RISK ASSESSMENT

23. CLINICAL PRESENTATION
Two-third are asymptomatic
Symptomatic patients present with:
• Fever
• Unilateral leg swelling
• Leg Pain
• Phlegmasia alba dolens
• Phlegmasia cerulea dolens
• Symptoms of PE

24. EXAMINATION
-Stretched and shiny skin
-Differential warmth positive
-Tense and tender limb swelling
-Unilateral pitting oedema (usually below the point of obstruction. )
-Superficial venous dilatation(varicose vein) may be observed
-Signs:
Homan’s sign
Moses sign
Neuhof
Lowenberg
These signs are non-specific and largely condemned.

26. INVESTIGATION
• Diagnostic; Invasive/ non invasive
Duplex USS,
Venography
CT, MRI
Intravascular USS
I125 Fibrinogen uptake
• D- dimer
• Clotting profile: PT, aPPT, INR
• FBC+ absolute Platelet count
• Assay: Protein c, Protein S, ATIII, Factor V.
• CXR in view of PE

27. D-DIMER ASSAY
Degradation product of fibrin
Measured via: ELISA, LLA, SimpliRED
Highly sensitive > 95%
Poor specificity

28. VENOUS ULTRASONOGRAPHY
- DVT likely patient
- Non invasive ,safe, available and inexpensive
- There are 3 types:
Compression ultrasound (B mode imaging)
Duplex ultrasound (doppler wave form analysis)
Colour doppler imaging
-Limitations

30. CONTRAST VENOGRAPHY
Definitive diagnostic test for DVT
-cannulation of pedal vein with
injection of a contrast medium
-Identifies location, extent and
attachment of a clot
-constant intraluminal filling
defect evident in 2 or more
views and abrupt cut off of
deep veins
-Abrupt cut off of a deep vein
-Limitations

31. IMPEDANCE PLETHYSMOGRAHY
Rate of change in impedance between 2
electrodes on the calf when a venous occlusion
cuff is deflated
- Delay in outflow of venous blood leads to a
more gradual change in the presence of DVT
-Its safe and non invasive
-Limitation: Not sensitive to small proximal
thrombi

32. MRI VENOGRAPHY
CT VENOGRAPHY

33. Diagnosis algorithm

34. DIFFERENTIAL DIGNOSIS

35. PREVENTION OF DVT
PRE-OP
• General measures
– Identify patient at risk
– Reduce weight before surgery
– Stop oral contraceptives 4 weeks before elective surgery
– Stop smoking
– Short pre-op hosp stay (< 72hrs)
– Deep breathing exercises
– Adequate hydration
• Mechanical
– Graduated compression stockings
– Intermittent pneumatic compression of calf
– Electrical calf muscle stimulation
• Chemical- drugs (high risk pts)
– Anticoagulation eg subcut Clexane

36. INTRA OP
• Pad pressure points
• Anaesthesia: Epidural
• Electrical stimulation of calf muscles
• External passive leg exercise using foot
paddling machine
• Adequate hydration

37. POST OP
• General measures
– Adequate hydration
– Deep breathing exercises
– Adequate analgesia
– Early mobilization
• Mechanical
– Graded elastic compression stockings
– Intermittent pneumatic leg compression
• Chemical- drugs
– Heparin- unfractionated, LMWH
– Warfarin; Fondaparinux
– Aspirin; Dextran

38. Unfractionated heparin (UFH)
 Natural; porcine intestine & bovine lung mucosa.
 Enhances Antithrombin III activity
-inactivates Xa, IIa, IXa, XIIa, antiplatelet activity, HIT
 Dose 5000units SC 8HRLY
• Monitoring with aPTT required; target 1.5× control.
 reversed with protamine sulphate(1mg/100units)
 Heparin prophylaxis is usually given for at least five days (the
minimum duration of prophylaxis in RCTs) or until hospital
discharge if earlier.
 safe throughout pregnancy & renal failure.

39. LMWH
• Natural source
• Indirect inhibitor of Xa by ↑ antithrombin III
• Enoxaparin, certoparin, tinzaparin, dalteparin etc.
• No monitoring of aPTT or INR required
• Safe in pregnancy, ↓ dose in renal failure
• OD dosing, S.C
• No antiplatelet activity, less HIT
• Less bleeding compared to UFH
• Partial reversal by protamine sulphate. ≠ FFP !!
• Expensive, but cost effective.
• Meta-analyses of RCTs have shown that subcutaneous
LMWHs have similar prophylactic efficacy to UFH

40. Warfarin
• Oral, OD dosing, 5mg, synthetic.
• Inhibits synthesis of Vit. K – dependent factors.
• Absolute C/I: pregnancy, non-compliance to Px or INR monitoring
• First, establish baseline INR, Initial therapy, Monitoring frequency.
• Target 2.5 (range: 2-3)
• Diverse drug, food interaction.
 ↓ dosing in renal failure
• Slow onset; 3-5 days
• Reversal with Vit.K – 5mg i.v slowly; 6hr onset. (- FFP 15mls/kg; immediate
onset.)

41. Rivaroxaban
• 1st Direct Xa inhibitor, synthetic.
• Oral, O.D dosing, 10mg
• No lab monitoring required
• No reversal agent
• Cost of Enoxaparin
↓ dosing in renal failure

42. Dabigatran
• Direct thrombin inhibitor
• Oral, synthetic
• O.D dosing, 220mg
• No specific antidote
• Lab monitoring not reqd.
• ↓ dosing in renal failure
• Cost of Enoxaparin

43. Fondaparinux ( ULMWH )
• Synthetic pentasaccharide
• Indirect Xa inhibitor, by ↑ antithrombin III activity
• No monitoring reqd
• OD dosing, Start 6hrs post-op, S.C, 2.5mg
• 2× cost of Enoxaparin
• No reversal agent. FFP ineffective ! !
• ↓ dosing in renal failure
• More effective, more bleeding > LMWH

44. Antiplatelets
• Low dose aspirin etc.
• Inhibits platelet activation & aggregation
• Cheap, oral.
• Reversal with platelet concentrate
• Low risk of bleeding
• Lab monitoring not required
• Effect continues for 7-10 days
• ↓ risk of PE > DVT.
• POOR RESULTS V. LMWH
• NOT RECOMMENDED ALONE FOR VTE IN ANY PATIENT GROUP

45. Dextrans
• DEXTRAN-70, DEXTRAN –40
• Plasma expander, ↓ viscosity, ↓stasis, Antiplatelet
• No monitoring reqd
• Effective for medium risk patients
 Easy & convenient, effective during surgery
• Risk of anaphylaxis.

46. Early ambulation
• Traditional method
• Ambulation addresses
only one component of
Virchow's triad, namely
venous stasis.
• Although desirable, it is
by itself not an
adequate prophylactic
measure for patients at
moderate or high risk.

47. GRADUATED ELASTIC COMPRESSION STOCKING
• Among the simplest of physical measures used.
• Properly fitted ES increase the velocity of blood
flow through the femoral veins.
• Effective in reducing the incidence of venous
clots, but only for patients at low risk.
• Thigh-length stocking should be preferred to
knee-length, substantial DVT develop above the
knee.
• Should be used in the appropriate manner

49. INTERMITTENT PNEUMATIC COMPRESSION(IPC)
• Important means of DVT prophylaxis.
• Made up of inflatable garment for the limb and electrical
pneumatic pump that fills the garment with compressed
air.
• Compare favorably with low-dose heparin.
• Pooled data show an incidence of DVT in 10 percent of
patients protected with IPC, representing a risk reduction
of 60 percent
• Not practicable in patients with fractures, plaster casts or
external fixation devices.

51. Venous foot pumps
• Useful when IPC devices or
stockings cannot be worn e.g.
trauma pts.
• It flattens metatarsal arch and
empties the plantar venous
plexus,reproducing the effect
of a normal weight bearing.
• Pt compliance better than in
the IPC devices.
• Risk of vessel injury is less,
pumps differ in speed and
pressure.

52. Inferior vena cava filters
• Inserted percutaneously under USS guidance
usually via the femoral vein.
• Placed in the IVC below the renal veins.
• Useful when anticoagulation is
contraindicated or pts who develop recurrent
VTE despite anticoagulation.
• Filters only prevent PE but do not halt the
thrombotic process.

54. Treatment
• Non operative:
-General measures
-Anticoagulation
-Thrombolysis (fribrinolysis)
• Operative:
-Minimally invasive
-Open venous thrombectomy

55. Non operative
• ANTI-COAGULATION
Heparin-Warfarin
Doses :
• Unfractionated Heparin 333units/kg subcut. followed by
250 units/kg twice daily
• Enoxaparin 1 mg/kg 12h hourly
• Enoxaparin 1.5 mg/kg daily
• Tinzaparin 175 IU/kg daily
• Dalteparin 100 IU/kg 12hourly
• Dalteparin 200 IU/kg daily

56. • FIBRINOLYSIS
– Now mainstay of therapy esp in early presentation
– However large thrombi and recent surgery are
unsuitable
– Two forms of recombinant tissue plasminogen
activator
• t-PA (alteplase)
• r-PA (reteplase)
– Urokinase
– Streptokinase

57. Operative
• Surgical Therapy
Preservation of patency AND valve function are the
main goals
 Minimally invasive
– Venous thrombectomy with Fogarty catheter
– Angioscopic thromboembolectomy
– Aspiration thromboembolectomy
– With/without adjunctive fibrinolytic infusion
 Open surgery

58. Fogarty catheter

60. Treatment timeline
Duration of therapy Indication
3-6months First event with reversible* or
time-limited risk factor
6 months or more Idiopathic venous
thromboembolism, first event
1 year to lifetime First event† with:
- Cancer, until resolved
- Anticardiolipin antibody
- Antithrombin deficiency
Recurrent event,
idiopathic or with
thrombophilia
* Surgery, trauma, immobilization, estrogen use.

61. Complications
• Pulmonary embolism
• Phlegmasia alba dolens
• Phlegmasia cerulea dolens
• Chronic Venous insufficiency
• Post phlebitic syndrome
• Recurrent DVT
• Varicose veins
• Complications of treatment

63. New trends
• M R A is being increasingly used to diagnose
DVT involving popliteal, common iliac and IVC
• Percutaneous retrievable IVC filters
• Newer agents : hirudin, lepirudin, idraparinux,
Bivalirudin, ximelagatran

64. Conclusion
• DVT is a common cause of morbidity and
mortality.
• Best prophylactic protocol for each patient
must be individualized, taking into account the
risk – benefit ratio.
• Even with optimal prophylaxis, VTE can & does
occur.
• VTE and DVT will remain a topical issue for
years to come.

65. References
• Brunicard F.C., Dana K.A., David L.D et al, 2015. Schwartz Principles Of Surgery .10th
Edn. McGraw Hill, New York.
• John L.C., Andrew M.C. , 2014. Current Surgical Therapy. 11th Edn, Elsevier Sanders,
Philadephia.
• E. Kesieme, C. Kesieme, E. Irekpita, A. Dongo. 2012. Deep Vein Thrombosis: A Clinical
Review , Journal of Blood Medicine 2012:2 .
https://www.researchgate.net/publication/221789439
• Kesieme E B, Arekhandia B J, Inuwa I M, Akpayak I C, Ekpe E E, Olawoye O A, Umar A,
Awunor N S, Amadi E C, Ofoegbu I J. 2016. Knowledge and practice of prophylaxis of
deep venous thrombosis: A survey among Nigerian surgeons. Niger J Clin Pract
2016;19:170-4
• Andre Biuckians; George H. Meier III. Treatment of Symptomatic Lower Extremity
Acute Deep Venous Thrombosis: Role of Mechanical Thrombectomy
http://www.medscape.com/viewarticle/567031_2

66. Thanks for listening