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• Venous thrombosis is significant cause of morbidity and mortality
• Pulmonary embolus accounts for 10 - 25 % of hospital deaths
• At least 20% patients with a DVT develop a post-thrombotic limb
• Most calf DVTs are clinically silent
• 80% of calf DVTs lyse spontaneously without treatment
• 20% of calf DVTs propagate to the thigh and have increased risk of PE

Pathophysiology

• Thrombus formation and propagation depends on the presence of Virchow's triad
  • Venous stasis
  • Hypercoagulable state
  • Endothelial damage
• Immobility contributes to venous stasis
• Endothelial damage can result from external compression
• A hypercoagulable state can be due to drugs or malignancy

Risk factors for venous thrombosis

• It is estimated that about 1:250 of the population have a congenital thrombophilia
• Potential for venous thrombosis can be investigated by a thrombophilia screen
  • FBC and blood film
  • >Clotting studies - APPT / PT / TT
  • Reptilase test
  • Protein C & S and Antithrombin III assay
  • Lupus anticoagulant

Epidemiology of DVT and pulmonary embolus

Risk of venous thrombosis during surgery

• Low risk
  • Minor surgery (<30 min) + no risk factors other than age
  • Major surgery (> 30 min) , age <40 yrs + no other risk factors
  • Minor trauma or medical illness
• Moderate risk
  • Major general, urological, gynaecological, cardiothoracic, vascular or neurological surgery + age >40 yrs or other risk factor
  • Major medical illness or malignancy
  • Major trauma or burn
  • Minor surgery, trauma or illness in patients with previous DVT, PE or thrombophilia
• High risk
  • Fracture or major orthopaedic surgery of pelvis, hip or lower limb
  • Major pelvic or abdominal surgery for cancer
  • Major surgery, trauma or illness in patient with previous DVT, PE or thrombophilia
  • Major lower limb amputation

Prevention of thromboembolism

Prevention of stasis

• Early mobilisation
• Graduate compression stockings
• Intermittent pneumatic compression (e.g. Flowtron boots)

Pharmacologically reduce hypercoagulable state

Heparin

• Acidic mucopolysaccharide
• Unfractionated heparin  (MW = 15 kDa)
• Low Molecular Weight Heparin  (MW = 5 kDa)
• Both potentiate Antithrombin III by inactivating activated clotting factors
• Unfractionated heparin  anti-Xa activity = anti IIa activity
• Low Molecular Weight Heparin  anti-Xa activity 4x > than anti IIa activity
• Does not have significant effect on APPT
• Side effects of unfractionated Heparin
  • Osteoporosis
  • Idiosyncratic thrombocytopenia

Warfarin

• Coumarin derivative & vitamin K antagonist
• Inhibits vitamin K dependent post translational carboxylation of factors II, VII, IX & X
• Graduated compression stockings reduce incidence of DVT by 50%
• No proven benefit of thigh-length compared to calf-length stockings
• Unfractionated and low molecular weight heparin are equally effective
• Reduce DVTs by 70% and PEs by 50%
• Unfractionated heparin usually given 5000u 3x daily
• Low Molecular Weight Heparin - Enoxaparin 20 or 40 mg daily

New drugs

• New drugs useful in DVT prophylaxis include
  • Thrombin inhibitors (e.g. hirudin)
  • Specific factor Xa inhibitors (e.g. fondaparinux)
• Factor Xa inhibitors may be more effective than LMWH

THRIFT recommendations

Current recommendations for DVT prophylaxis

• All hospital inpatients
• Should be assessed for clinical risk factors and overall risk of thromboembolism
• Should receive prophylaxis according to degree of risk
• Prophylaxis should continue until discharge
• Low risk patients should be mobilised early
• Moderate risk patients should receive specific prophylaxis

NICE Guidelines (2007)

Information and assessment

• Assess patients for individual risk of venous thromboembolism
• Advice patients to stop taking OCP for 4 weeks prior to elective surgery
• Inform patients that immobility (travel of more than 3 hours) in the 4 weeks before or after surgery increases risk
• Before surgery give verbal and written information on:
  • Risk of DVT
  • Effectiveness of prophylaxis
• As part of each patient's discharge plan give information on
  • Signs and symptoms of DVT
  • Correct use of prophylaxis at home
  • Implications of not using prophylaxis

Mechanical prophylaxis

• Unless contraindicated, offer all inpatients thigh-length compressions stockings
• The stocking profile should be
  • 18 mmHg at the ankle
  • 14 mmHg at the mid-calf
  • 8 mmHg at the upper thigh
• Staff should be trained in the use and fitting of the stockings
• Stockings should be worn from the time of admission until the resumption of normal mobility
• Intermittent pneumatic compression devices should also be used

Pharmacological prophylaxis

• Patients at increased risk of DVT should be offered LMWH
• The risks and benefits of stopping anticoagulation or anti-platelet therapy should be considered
• Careful planning of the timing of prophylaxis should be given in those undergoing regional anaesthesia

Other strategies

• Do not allow patients to become dehydrated whilst in hospital
• Consider regional anaesthesia if appropriate
• Consider vena caval filters if patient has existing or recent DVT
• Encourage early mobilisation

Clinical features of DVT

• Clinical presentation of a DVT can be very non-specific
• Many are asymptomatic
• Clinical features depends on site of venous occlusion
• Classical clinical features of a calf DVT are:
  • Calf pain and tenderness
  • Pyrexia
  • Persistent tachycardia
• Homan's sign = pain on passive dorsiflexion of the ankle is a non-specific sign
• Occlusion of the ileo-femoral vein can result in venous gangrene (phlegmasia cerulea dolens)

Picture provided by Chris Malkin, Leeds General Infirmary, Leeds, United kingdom

Investigation of suspected DVT

• Less than 50% of those suspected of having DVT have clot identified on imaging

D-dimers

• A fibrin degradation product that can be assayed in plasma
• Levels raised in the presence of recent thrombus
• A negative result almost excludes the presence of venous thrombosis
• Decision to proceed to venography or ultrasound often based on D-dimer result

Venography

• Gold standard
• Will identify both calf vein and proximal thrombus
• Painful and time consuming investigation.
• 2-3% of patients develop contrast reaction

Ultrasound

• Technique has three components - all operator dependent.
  • Venous compressibility
  • Detection of Doppler flow
  • Visualisation of clot
• In femoro-popliteal segment - sensitivity = 94%. specificity = 100%
• In calf veins - sensitivity = 73%. specificity = 86%
• Able to exclude femoro-popliteal or major calf DVT in symptomatic patients

Treatment of venous thrombosis

• Aims of treatment:
  • Prevention of pulmonary embolus
  • Restore venous and valvular function to prevent the post thrombotic limb
• Few aspects of treatment submitted to RCTs

Anticoagulation

• Main component of treatment
• Initially with unfractionated or low molecular weight heparin
• Followed by oral anticoagulation
• LMWHs have increased bioavailability and linear kinetics
• The treatment of isolated calf DVTs is of unproven benefit
• Optimal duration of treatment unknown
• No proof that treatment beyond 3-6 months is required

Surgical thrombectomy

• Considered in massive ileo-femoral thrombosis associated with phlegmasia cerulea dolens
• Good early results with 62% complete and 38% partial clearance of ileo-femoral segment
• Unfortunately re-occlusion common
• Thrombolysis of unproven benefit

Pulmonary embolism

• Accounts for 3% of hospital inpatients deaths
• Untreated has a mortality of 30%
• Treated mortality reduced to about 2%
• Only 10% have clinical signs of a DVT

Clinical presentation

Investigations of possible pulmonary embolus

• Arterial blood gases - hypoxia, hypocarbia but may be normal
• ECG - Signs of right heart strain - classically S₁Q₃T₃
• CXR - Show oligaemia and central pulmonary markings and excludes other pathologies
• Ventilation / Perfusion scanning - May confirm or refute diagnosis
• Pulmonary angiography and echocardiography useful if haemodynamic instability
• Spiral CT might replace pulmonary angiography
• Lower limb investigations for DVT as above

Management of pulmonary embolus

• Depends on degree of suspicion and haemodynamic stability
• If high degree of suspicion but stable:
• Anti-coagulate with heparin or LMWH
• Oxygen, analgesia, colloid to increase CVP
• Warfarinise for at least 3 months
• If haemodynamically unstable:
• Consider pulmonary thrombolysis via pulmonary artery catheter
• If thrombolysis contraindicated consider pulmonary embolectomy

Inferior vena caval filters

• Inserted percutaneously usually via femoral vein
• Present a physical barrier to emboli
• Indicated if:
  • Recurrent pulmonary emboli despite adequate anti-coagulation
  • Extensive proximal venous thrombosis and anticoagulation is contraindicated

Bibliography

Agu O,  Hamilton G,  Baker D.  Graduated compression stockings in the prevention of venous thromboembolism.  Br J Surg 1999;  86:  992-1004.

Bergqvist D.  Lowe molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery.  Br J Surg 2004;  91:  965-974.

Bergqvist D.  Prevention of venous thromboembolism after surgery: a review of enoxaparin.  Br J Surg 1992; 79:  495-498.

Grace R,  Hunt B J.  Thromboprophylaxis.  Br J Hosp Med 1993; 49: 720-726.

Goldhaber S Z.  Pulmonary embolism.  Lancet 2004;  363:  1295-1305

Hampton K K.  Pathophysiology of venous thromboembolism. Hosp Med 2001;  62:  675-672.

Jorgensen L N,  Willie-Jorgensen P, Hauch O.  Prophylaxis of postoperative thromboembolism with low molecular weight heparins.  Br J Surg 1993; 80:  689-704.

Lensing A W A,  Prandoni P,  Prins M H,  Buller H R.  Deep vein thrombosis.  Lancet 1999;  353:  479-485.

Menon K V,  Insall R L,  Ignotus P I.  Inferior vena caval filter:  an overview of current use.  Hosp Med 1998;  59:  224-226.

Mills T D,  Chan O,  Matson M.  The use of vena caval filters.  Hosp Med 2001;  62: 327-331.

Mismetti P,  Laporte S,  Darmon J-Y,  Buchmuller A,  Decousus H.  Meta-analysis of low molecular heparin in the prevention of venous thromboembolism in general surgery.  Br J Surg 2001;  88:  913-930.

Sissons G R J.  Investigation of suspected lower limb venous thrombosis.  Ann R Coll Surg Eng 1998;  80:  49 –54.

Tai N R M,  Atwal A S,  Hamilton G.  Modern management of pulmonary embolism.  Br J Surg 1999;  86:  853-868.

Thromboembolic Risk Factors (THRIFT) Consensus Group.  Risk of and prophylaxis for venous thromboembolism in hospital patients.  Br Med J  1992; 305:  567-574.

Turpie A G G,  Chin B S P, Lip G Y H.  Venous thromboembolism:  pathophysiology, clinical features and prevention.  Br Med J 2002:  325:  887-890.

Walker I D,  Greaves M,  Preston F E.  Guidelines:  Investigation and management of heritable thrombophilia.  Br J Haematol 2001;  114:  512-528.

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Last updated: 05 January 2008

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