Tackling venous thromboembolism

Each year in England, 25,000 people die from venous thromboembolism (VTE), a term used to describe deep vein thrombosis and pulmonary embolism.

VTE is the formation of a blood clot (thrombus) in a vein that may dislodge from its site of origin to cause an embolism. Most thrombi occur in the deep veins of the legs – this is called deep vein thrombosis (DVT). Dislodged thrombi may travel to the lungs – this is called a pulmonary embolism (PE), and can be fatal.

Thrombi can also cause long-term morbidity due to venous insufficiency and post-thrombotic syndrome, potentially leading to venous ulceration.

The formation of thrombi is associated with inactivity and surgical procedures. The risk rises with the duration of the operation and period of immobility. Potentially a killer, DVT occurs in about 30% of surgical patients. The condition can lead to sudden death due to the resulting pulmonary embolism (the cause of death in 10% of patients who die in hospital), or can cause long-termillness due to venous ulceration and the development of a postthrombotic limb.

The NICE guidelines examine the risk of VTE in inpatients undergoing various surgical procedures and include the measures that should be adopted, as follows:

• Elective orthopaedic surgery (for example, total hip or knee replacement): Patients should be offered mechanical prophylaxis and either low molecular weight heparin (LMWH) or fondaparinux. Those having hip replacement surgery with one or more risk factors (see Fig. 1) should have their LMWH or fondaparinux therapy continued for four weeks after surgery.

• Hip fracture surgery: Patients should be offered mechanical prophylaxis and either LMWH or fondaparinux. LMWH or fondaparinux therapy should be continued for four weeks after surgery.

• General surgery: Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and either LMWH or fondaparinux.

• Gynaecological surgery (excluding Caesarean section): Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH.

• Cardiac surgery: Patients should be offered mechanical prophylaxis. Those who are not otherwise receiving anticoagulation therapy and who have one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH.

• Thoracic surgery: Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH.

• Urological surgery: Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH.

• Neurosurgery (including spinal surgery): Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH. Patients with ruptured cranial or spinal vascular malformations (e.g. brain aneurysms) should not be offered pharmacological prophylaxis until the lesion has been secured.

• Vascular surgery: Patients should be offered mechanical prophylaxis. Those with one or more risk factors of VTE should be offered mechanical prophylaxis and LMWH.

N.B. The term mechanical prophylaxis covers graduated compression/antiembolism stockings, intermittent pneumatic compression devices and foot impulse devices.

Healthcare professionals are advised to exercise their clinical judgement when making decisions on the appropriateness of VTE prophylaxis in relation to other surgical procedures that require an inpatient stay.

The guidelines do not cover patients aged under 18 years or adult patients who are at a high risk of developing VTE but are not undergoing surgery. For example, the following circumstances and patients are excluded from the guideline, unless patients are undergoing one of the surgical procedures listed above:

• Patients with acute myocardial infarction.
• Patients who have had an acute stroke.
• Patients with cancer, including those being treated with chemotherapy.
• Pregnancy and the puerperium.
• Use of oral contraceptives and hormone replacement therapy.
• Long-distance travel.

PATIENT-CENTRED CARE

The guidelines recommend that treatment and care should take into account patients’ needs and preferences. People undergoing surgery that requires an inpatient stay should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. If patients do not have the capacity to make decisions, healthcare professionals should follow the Department of Health guidelines: ‘Reference guide to consent for examination or treatment’ (2001).

Good communication between healthcare professionals and patients is described as being essential. It should be supported by evidence-based written information tailored to the patient’s needs. Treatment and care, and the information patients are given about it, should be culturally appropriate. It should also be accessible to people with additional needs such as physical, sensory or learning disabilities, and to people who do not speak or read English. Furthermore, carers and relatives should have the opportunity to be involved in decisions about the patient’s care and treatment, unless the patient specifically excludes them. Carers and relatives should also be given the information and support they need.

KEY PRIORITIES FOR IMPLEMENTATION

• Patients should be assessed to identify their risk factors for developing venous thromboembolism (see Fig. 1). They should also be given verbal and written information, before surgery, about the risks of VTE and the effectiveness of prophylaxis.

• Inpatients having surgery should be offered thigh-length graduated compression/anti-embolism stockings from the time of admission to hospital unless contraindicated (for example, in patients with established peripheral arterial disease or diabetic neuropathy).

If thigh-length stockings are inappropriate for a particular patient for reasons of compliance or fit, knee-length stockings may be used as a suitable alternative.

• The stocking compression profile should be equivalent to the Sigel profile, and approximately 18 mmHg at the ankle, 14 mmHg at the mid-calf and 8 mmHg at the upper thigh.

• Patients using graduated compression/ anti-embolism stockings should be shown how to wear them correctly and the use of the stockings should be monitored and assistance provided if they are not being worn correctly.

• Intermittent pneumatic compression or foot impulse devices may be used as alternatives or in addition to graduated compression/anti-embolism stockings while surgical patients are in hospital.

• In addition to mechanical prophylaxis, patients at increased risk of VTE because they have individual risk factors (see Fig. 1) and patients having orthopaedic surgery should be offered LMWH. Fondaparinux, within its licensed indications, may be used as an alternative to LMWH.

• Regional anaesthesia reduces the risk of VTE compared with general anaesthesia. Its suitability for an individual patient and procedure should be considered, along with the patient’s preferences, in addition to any other planned method of thromboprophylaxis.

• Patients should be encouraged to mobilise as soon as possible after surgery.

Healthcare professionals are advised to give patients verbal and written information, before surgery, about the risks of VTE and the effectiveness of prophylaxis. They should also inform patients that the immobility associated with continuous travel of more than three hours in the four weeks before or after surgery may increase the risk of VTE. Relevant patients should also be asked to consider stopping combined oral contraceptive use four weeks before elective surgery and further verbal and written information should be given to all patients as part of their discharge plan. Advice should be given on the signs and symptoms of DVT and PE, the correct use of prophylaxis at home, and the implications of not using the prophylaxis correctly.

IMPLEMENTATION IN THE NHS

NICE has developed a set of tools to help organisations implement their guidelines.

These are available on its website, and can be found at: www.nice.org.uk/CG046 .

They include:

• Slides highlighting key messages for local discussion.

• Costing tools

• Implementation advice on how to put the guidance into practice and national initiatives that support this locally.

• Audit criteria to monitor local practice.

FUTURE RESEARCH RECOMMENDATIONS

There are three different areas that NICE recommends for further research in order to improve its guidance and patient care in the future.

The first of these relates to the incidence of clinical deep vein thrombosis, confirmed pulmonary embolism, major bleeding, and other post-operative adverse outcomes in modern surgical practice. The aim should be to recruit patients undergoing a range of surgical procedures with different levels of expected risk of VTE, ensuring coverage of the common operations currently performed in the NHS. Baseline evaluation would aim to identify risk factors for VTE and for other adverse outcomes (for example, bleeding and occlusive vascular events). The study would also record any in-hospital drug treatment and discharge medication. It is important to note, however, that this would be a large observational cohort study and would not be appropriate for determining the effects of treatment, because moderate effects cannot be assessed reliably by such studies. The control (reference) group will be defined for each parameter (for example, age) by a category of patients at low risk of VTE (for example, age younger than 30 years).

This research is considered important because the chief difficulty faced when formulating the present guideline was the absence of accurate estimates of VTE risk in the modern era. Although it was possible to estimate the relative risk reductions associated with particular interventions, it was not possible to estimate their associated absolute benefits. It is possible that the modern risks of VTE are much lower than is represented by the available trial evidence because of changes in anaesthetic practice and earlier mobilisation. Information on absolute risks of VTE (and other post-operative complications) needs to be obtained in order to assess cost effectiveness reliably. Information from this study would help surgical teams to provide their patients with accurate information about the balance of benefit and risk associated with particular interventions.

This study could be performed easily if the design elements were kept simple, with one-sided forms that could be completed by junior staff at discharge, and follow-up through mailed questionnaires and tracking of mortality via the Office of National Statistics.

The second area of study concerns the timing of administration of low molecular weight heparin.

What is the effectiveness of low molecular weight heparin (LMWH) started pre-operatively compared with LMWH started post-operatively, in reducing the risk of (objectively diagnosed) DVT or PE in adult patients undergoing inpatient surgical procedures?

All patients should be screened for the presence of DVT and/or PE. Secondary outcomes of interest are costs, quality of life and other adverse events (for example, myocardial infarction, stroke, extracranial or intracranial bleeding).

NICE considers this research to be important because the currently available randomised evidence is too limited to determine whether giving LMWH can be safely delayed until after surgery, or whether it must be given pre-operatively. The current guidelines recommend that LMWH is used for many patients at risk of VTE and is therefore non-specific about timing. This is a major gap in the evidence.

Although there may be only small differences in safety and efficacy between these two strategies, a policy of giving LMWH post-operatively may reduce the time that patients need to be in hospital before surgery and therefore have major benefits for patients.

As there is uncertainty around this question, it should be possible to find surgeons willing to randomise between these two strategies. The principal practical difficulty with this randomised trial would be the need for a very large sample size (with possibly more than 10,000 patients), because the likely differences in DVT/PE and bleeding rates are small.

Finally, the effectiveness of combining methods of mechanical prophylaxis is considered to be another important area that merits further research. What is the effectiveness of graduated compression/anti-embolism stockings and either an intermittent pneumatic compression (IPC) device or a foot pump device, compared with graduated compression/anti-embolism stockings alone, in reducing the risk of (objectively diagnosed) DVT and/or PE in adult inpatients undergoing surgery? Patients may be at risk of VTE because of the procedure (for example, hip fracture), or because they have risk factors for such disease (for example, thrombophilia or age over 60 years).

All patients should be screened for the presence of DVT and/or PE.

Randomisation would be stratified into two groups: patients in whom pharmacological prophylaxis is contraindicated (for example, because of an increased risk of bleeding); and patients in whom pharmacological prophylaxis is indicated, but the risk of VTE is very high.

Secondary outcomes would be costs, quality of life, skin problems, myocardial infarction, stroke and other adverse events (for example, bleeding).

This research is important because only a small number of randomised controlled trials have evaluated a combination of mechanical methods. These studies have shown promising results, but have involved small numbers of patients, and the large effect sizes observed in some of these studies suggest bias.

This trial would also inform the management of two specific groups of patients in whom the available treatment options are restricted: patients at high risk of VTE who cannot have LMWH because they are at increased risk of bleeding; and patients at very high risk of VTE who can be given pharmacological prophylaxis and who might benefit from combination mechanical thromboprophylaxis.

This trial would help extend the current NICE recommendations. There may be cost savings if the addition of a second mechanical method results in further risk reduction of VTE.

The proposed research is feasible but depends on the extent to which surgeons are certain about the value of combining two mechanical methods of thromboprophylaxis, because this would determine their willingness to randomise. Before any trial this issue would need to be explored in detail, possibly via a questionnaire.

FURTHER INFORMATION

1 The full guideline, Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery contains details of the methods and evidence used to develop the guidelines. It is published by the National Collaborating Centre for Acute Care, and is available from: www.rcseng.ac.uk/ surgical_research_units/nccac, the NICE website at: www.nice.org.uk/ CG046fullguideline, and the National Library for Health (www.nlh.nhs.uk).

2 A quick reference guide for healthcare professionals is also available from: www.nice.org/CG046quickrefguide For printed copies, phone the NHS Response Line on 0870 1555 455 (quote reference number N1216).