Prevention of venous thromboembolism

See the related separate articles on Thrombophilia, Pulmonary Embolism, and Deep Vein Thrombosis.

Clinicians are frequently asked to advise patients on prophylactic measures to minimise the risk of venous thromboembolism (VTE). The National Institute for Health and Care Excellence (NICE) has produced guidelines to assist in reducing the risk.¹

The following surgical procedures are high-risk:

• Orthopaedic surgery (for example, total surgery for hip fracture).

• Major general surgery.

• Major gynaecological surgery (but not caesarean).

• Urological surgery (including major or open urological procedures).

• Neurosurgery.

• Cardiothoracic surgery.

• Major peripheral vascular surgery.

Assessing the risk for venous thromboembolism¹

Lifestyle risk factors that increase the risk of unprovoked VTE include obesity, physical inactivity, current smoking and Western diet.²

Patients should be assessed individually, both considering any existing risk factors for VTE, and their risk of bleeding. A decision can then be made as to whether VTE prevention should be offered and, if so, whether this should be pharmacological, mechanical or both. For patients with increased risk, the balance of risk versus benefits of treatment should be reassessed at regular intervals. For patients in hospital this should be 24 hours after admission or whenever there is a change in the clinical situation.

Risk factors for VTE¹

• Active cancer or cancer treatment.

• Age over 60 years.

• Critical care admission.

• Dehydration.

• Known thrombophilia.

• Obesity (body mass index (BMI) over 30 kg/m²).

• One or more significant medical comorbidities (eg, heart disease, metabolic, endocrine or respiratory illness, acute infectious diseases, inflammatory conditions).

• Personal history or a first-degree relative with a history of VTE.

• Use of hormone replacement therapy (HRT) or oestrogen-containing contraceptive therapy.

• Varicose veins with phlebitis.

• Women who are pregnant or have given birth within the previous six weeks.

Admissions to hospital¹

Assess all patients on admission to hospital to identify those who are at increased risk of VTE. Regard medical patients as being at increased risk of VTE if they:

• Have had or are expected to have significantly reduced mobility for three days or more; or

• Are expected to have ongoing reduced mobility relative to their normal state and have one or more of the risk factors shown above.

Regard surgical patients and patients with trauma as being at increased risk of VTE if they meet one of the following criteria:

• Surgical procedure with a total anaesthetic and surgical time of more than 90 minutes, or 60 minutes if the surgery involves the pelvis or lower limb.

• Acute surgical admission with inflammatory or intra-abdominal condition.

• Expected significant reduction in mobility.

• One or more of the risk factors shown above.

Prevention of venous thromboembolism¹

Always refer to local or regional guidelines when available.

All patients

• Avoid dehydration unless there is a specific clinical reason.

• Encourage early mobilisation.

• Aspirin or antiplatelet agents should not be considered adequate prophylaxis.

• There are no randomised controlled trials or controlled clinical trials that have assessed the benefit(s) of testing for thrombophilia on the risk of recurrent VTE.³

Choice of prophylaxis

Mechanical
Several methods are available:

• Graduated compression stockings are effective in decreasing the risk of DVT, either alone or in combination with pharmacological prophylaxis in high-risk patients. Thigh-length graduated compression/anti-embolism stockings can be used unless contra-indicated (see below). Graduated compression stockings should be used routinely for surgical inpatients. If thigh-length stockings are not appropriate (for reasons of fit or compliance) knee-length stockings may be used instead:⁴

• Anti-embolism stockings should not be offered to people who have:
  

  • Suspected or proven peripheral arterial disease.

  • Peripheral arterial bypass grafting.

  • Peripheral neuropathy or other causes of sensory impairment.

  • Any local conditions in which anti-embolism stockings may cause damage, eg, fragile skin, dermatitis, gangrene or recent skin graft.

  • Known allergy to material of manufacture.

  • Severe leg oedema.

  • Major limb deformity or unusual leg size or shape preventing correct fit.

• Intermittent pneumatic compression or foot impulse devices may be used instead of, or as well as, graduated compression stockings while patients are in hospital. They should be used for as long as practical prior to surgery.

Pharmacological
Choice should depend on comorbidities (eg, chronic kidney disease), a patient's wishes and local policies. Options include:

• Fondaparinux sodium.

• Low molecular weight heparin (LMWH) - synthetic alternatives may be more acceptable to patients who want a non-animal based product.

• If using pharmacological VTE prophylaxis for people with renal impairment, choose either LMWH or unfractionated heparin (UFH), but, if needed, reduce the dose of LMWH or UFH. Always refer to local or regional guidelines.

If pharmacological VTE prophylaxis is indicated, start as soon as possible after risk assessment. Always also consider the risk of bleeding. Risk factors for bleeding include:¹

• Active bleeding.

• Acquired bleeding disorders (eg, acute liver failure).

• Concurrent use of anticoagulants known to increase the risk of bleeding (such as warfarin with international normalised ratio (INR) higher than 2).

• Lumbar puncture/epidural/spinal anaesthesia expected within the next 12 hours.

• Lumbar puncture/epidural/spinal anaesthesia within the previous 4 hours.

• Acute stroke.

• Thrombocytopenia (platelets less than 75 x 10⁹/L).

• Uncontrolled systolic hypertension (230/120 mm Hg or higher).

• Untreated inherited bleeding disorders (eg, haemophilia, von Willebrand's disease).

High-risk patients

High-risk patients (eg, multiple risk factors, especially previous DVT/PE) should be offered:

Mechanical prophylaxis
Several methods are available:

• Graduated compression stockings are effective in decreasing the risk of DVT, either alone or in combination with pharmacological prophylaxis in high-risk patients. Thigh-length graduated compression/anti-embolism stockings can be used unless contra-indicated (eg, in patients with established peripheral arterial disease or diabetic neuropathy).

• Patients should be encouraged to wear stockings from admission until they return to their normal level of mobility.

• Intermittent pneumatic compression or foot impulse devices may be used instead of, or as well as, graduated compression stockings while patients are in hospital. They should be used for as long as practical prior to surgery.

Pharmacological prophylaxis⁵

• Patients with high risk and those having orthopaedic surgery should also be offered LMWH. Fondaparinux, within its licensed indications, is an effective and safe alternative.

• The direct oral anticoagulants (DOACs) apixaban, dabigatran etexilate, and rivaroxaban are licensed for thromboprophylaxis following hip or knee replacement surgery (see above).

• Consideration should be given to the risks and benefits of stopping pre-existing anticoagulation or antiplatelet therapy before surgery.

• Pharmacological prophylaxis may need to be stopped if regional anaesthesia is employed in order to minimise the risk of haematoma.⁶

Other options

• Patients should be encouraged to maintain their fluid intake and not become dehydrated during their stay in hospital.

• Regional anaesthesia is to be preferred if possible as it is less of a risk for VTE than general anaesthesia.

• Patients should be encouraged to mobilise, or leg exercises should be arranged if they are immobile, as soon as possible after surgery.

Prophylactic inferior vena cava (IVC) filters⁷
Prophylactic IVC filters are sometimes inserted in patients at high risk of developing venous thromboembolism, especially if there is a contraindication to anticoagulation.

However, a systematic review and meta-analysis of the published reports on the efficacy and safety of IVC filters concluded that:

• There were very few prospective controlled studies, with limited quality of evidence, regarding the efficacy and safety of IVC filters.

• Overall, filters appear to reduce the risk of subsequent PE, increase the risk for DVT, and have no significant effect on overall mortality.

Patients with no risk factors

Patients having hip replacement, surgical treatment of hip fractures and other kinds of major orthopaedic surgery should be offered mechanical and pharmacological prophylaxis. Otherwise, only mechanical prophylaxis is required.

Specific clinical scenarios

Details of the management of various clinical scenarios can be found in the NICE clinical guideline 'Venous thromboembolism in over 16s'. See reference link below.

Patients having elective surgery

• Oral contraceptives or HRT containing oestrogen should be stopped four weeks before surgery.

• For patients on antiplatelet therapy, balance the risks versus benefits of stopping one week before surgery (involve other clinical colleagues as necessary).

• Regional anaesthesia carries less risk than general; consider the patient's wishes, suitability and any other planned methods of VTE prophylaxis.

• If using regional anaesthesia consider timing of pharmacological prophylaxis to minimise risk of epidural haematoma; refer to standard product characteristics for the optimum timing of antiplatelet or anticoagulant prophylaxis with regard to regional anaesthesia.

• Prophylaxis is unnecessary in patients having local anaesthesia by local infiltration if there is no restriction in mobility.

• Choice of prophylaxis will depend on the type of surgery, suitability for the patient, and local policy.

• Apixaban, rivaroxaban and dabigatran are recommended by NICE as options for the prevention of venous thromboembolism in adults after elective hip or knee replacement surgery.^{8 9 10}

• Elective hip replacement:

  • Thromboprophylaxis with either a LMWH for 10 days followed by low-dose aspirin for a further 28 days, or a LMWH for 28 days in combination with anti-embolism stockings until discharge, or rivaroxaban.

  • If these options are unsuitable, apixaban or dabigatran can be considered as alternatives. If pharmacological prophylaxis is contra-indicated, anti-embolism stockings can be used until discharge.

• Elective knee replacement:

  • Thromboprophylaxis with either low-dose aspirin for 14 days, or a LMWH for 14 days in combination with anti-embolism stockings until discharge, or rivaroxaban.

  • If these options are unsuitable, apixaban or dabigatran etexilate can be considered as alternatives. If pharmacological prophylaxis is contra-indicated, intermittent pneumatic compression can be used until the patient is mobile.

Patients being discharged from hospital
Verbal and written information should be given to the patient/carer on:

• Signs and symptoms of DVT and PE.

• Correct use of prophylaxis at home.

• Implications of not using prophylaxis correctly.

Patients already having antiplatelet or anticoagulant therapy to treat other conditions

• Offer prophylaxis (pharmacological or mechanical) if the risk of thrombosis outweighs the risk of bleeding.

• Prophylaxis should not be offered to patients taking vitamin K antagonists (who are within therapeutic range) or DOACs, providing anticoagulant therapy is continued.

• Patients on full anticoagulant therapy should not be offered additional prophylaxis - pharmacological or mechanical.

People with cancer

• Do not offer VTE prophylaxis to people with cancer who are receiving cancer-modifying treatments such as radiotherapy, chemotherapy or immunotherapy and who are mobile, except as outlined below, unless they are also at increased risk of VTE because of something other than the cancer.

• Consider pharmacological VTE prophylaxis for people with myeloma who are receiving chemotherapy with thalidomide, pomalidomide or lenalidomide with steroids. Choose either aspirin (75 mg or 150 mg) or LMWH.

• Consider pharmacological VTE prophylaxis with LMWH for people with pancreatic cancer who are receiving chemotherapy.

• If giving VTE prophylaxis to people with cancer, continue for as long as they are receiving chemotherapy.

People having palliative care

• Consider pharmacological VTE prophylaxis for people who are having palliative care. Take into account temporary increases in thrombotic risk factors, risk of bleeding, likely life expectancy and the views of the person and their family members or carers.

• Use LMWH as first-line treatment. If LMWH is contraindicated, use fondaparinux sodium.

• Do not offer VTE prophylaxis to people in the last days of life.

• Review VTE prophylaxis daily for people who are having palliative care, taking into account the views of the person, their family members or carers and the multidisciplinary team.

Acute stroke

• Anti-embolism stockings should not be offered.

• If risk of bleeding is low, consider intermittent pneumatic compression for VTE prophylaxis for people who are immobile and admitted with acute stroke. Start it within 3 days of acute stroke.

• If risk factors suggest high risk of VTE (eg, significant restriction to mobility, previous history of VTE, malignancy) and haemorrhagic stroke has been excluded, consider LMWH or UFH.

• If there is low risk of VTE, reassess in 24 hours.

Pregnancy¹¹
See also the article Venous Thromboembolism in Pregnancy.

• Pre-pregnancy counselling and a management plan should be offered to all women who are at high risk of VTE.

• All pregnant women should have their risk factors assessed and documented.

• This assessment should be repeated if there is a hospital admission for any reason or if complications develop.

• Thrombophilia should be excluded in women with a previous non-oestrogen-related VTE which has been provoked by a minor risk factor.

• LMWH is the prophylaxis of choice, being safer and equally effective as UFH.

Details of risk assessment and when prophylaxis should start and end (dependent on risk factors) is included within the RCOG guideline 'Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium' (see references for link).

Travel-related deep vein thrombosis¹²

Assessing risk

The absolute risk of an individual developing a travel-related DVT remains low even if they are at high risk. In addition to travel itself, risk factors include:

• Active malignancy.

• Family history of DVT or pulmonary embolism (PE) in a close family member.

• Aged over 60 years.

• Extremes of height: people taller than 1.90 metres or shorter than 1.60 metres.

• Inherited blood-clotting abnormalities.

• Large varicose veins or chronic venous insufficiency.

• Limited mobility.

• Obesity.

• Polycythaemia.

• Pregnancy, or up to six weeks postpartum.

• Previous DVT or PE.

• Recent surgery or trauma, particularly to the abdomen, pelvic region, or legs.

• Thrombophilia (such as factor V Leiden mutation or antiphospholipid syndrome), or other thrombotic states (eg, heart failure, recent myocardial infarction, severe infection, inflammatory bowel disease).

• Use of oestrogens, such as oral contraceptives or hormone replacement therapy.

For continuous journeys lasting more than six hours, the risk of travel-related DVT can be considered as:

• High risk of travel-related DVT if they have:

  • An active malignancy.

  • Undergone recent major surgery (within the previous 4 weeks).

  • Had a previous unprovoked venous thromboembolism (VTE).

  • Had a previous travel-related DVT with no associated temporary risk factor.

  • More than one risk factor for DVT.

• Moderate risk if they have one risk factor and are not considered at high risk.

• Low risk if they have no pre-existing risk factors.

Management

General advice

• Avoid periods of prolonged immobility; take occasional short walks around the cabin whilst the aircraft is cruising at altitude.

• Wear loose-fitting clothing. Sit comfortably in the seat and recline as much as possible.

• While seated, bend and straighten legs, feet, and toes every 30 minutes during the flight. Press the balls of the feet down hard against the floor or footrest to increase the blood flow in the legs and reduce clotting. Do upper body and breathing exercises to further improve circulation.

• Maintain a normal fluid intake and avoid excessive alcohol. Avoid taking sleeping pills.

• Seek urgent medical advice if they develop the following after the trip: swollen, painful legs, especially where one is more affected than the other, and/or breathing difficulties

• For people assessed as having relatively moderate or high risk (see below), advise the use of graduated compression stockings. Advise the use of below-knee graduated stockings with an appropriate compression.

• Aspirin is not recommended for the prevention of travel-related DVT. People already taking aspirin should not increase their dose.

People at low risk: advice on general measures to reduce the risk of travel-related DVT. No specific treatment is required.

People at moderate risk
Provide advice on general measures to reduce the risk of travel-related DVT. Advise graduated compression stockings: class 1 stockings or proprietary flight socks are generally sufficient. Measure the ankle-brachial pressure index (ABPI) if the person has symptoms of arterial disease. If the ABPI is less than 0.8, compression stockings should not be worn.

People at high risk
Assess the person's suitability for long-distance travel. Consider seeking specialist advice, or recommend delaying or cancelling the trip (eg, postpone a long-haul flight for three months after a hip or knee replacement). If travelling is unavoidable and involves continuous travel lasting more than six hours:

• Provide general advice on general measures and the use of graduated compression stockings as for people at moderate risk.

• Seek specialist advice from a haematologist regarding whether the use of LMWH is indicated:
  

  • LMWH should be administered before departure.

  • Provide the person with a letter that explains why they have to carry needles and syringes while travelling, to show to security, immigration, and customs officials. Warn about the increased risk of bleeding and bruising.

  • Advise the person to seek urgent medical advice if there is uncontrolled or excessive bleeding or bruising, or if they have a sudden severe headache or gastrointestinal pain.

• DOACs may also be used on the recommendation of a haematologist. There are no trials evaluating the use of DOACs for travel-related VTE prophylaxis. However, it has been argued that, since DOAC-only treatment (without LMWH) is now commonly used for the treatment of VTE, a DOAC could replace LMWH in this situation.¹³

Joint replacement or fracture
Advise to postpone long-haul flights until three months after surgery.

Fracture
Advise people with a plaster cast to have this changed to a split cast to reduce the risk of compression.

Recent DVT

• If the person has a new diagnosis (within two weeks) of DVT or PE, seek specialist advice.

• If the person has been taking anticoagulants for two weeks or more: reassure that they are at low-risk of developing a further thrombosis. Provide advice on general measures to reduce the risk of travel-related DVT. Consider prescribing graduated compression stockings.