Professor Samuel Machin discusses the implications for primary care of NICE recommendations on long-term prophylaxis for venous thromboembolism after hip surgery


The NICE clinical guideline on Venous thromboembolism was published in April 2007.1,2 It advises that, in addition to mechanical methods, patients at increased risk of venous thromboembolism (VTE) (see Box 1), as well as those having orthopaedic surgery, should be offered daily prophylaxis with low molecular weight heparin (LMWH).1,2 Within its licensed indications, fondaparinux, a factor Xa inhibitor, may be used as an alternative to LMWH.1,2

Box 1: Patient-related risk factors for venous thromboembolism

  • Active cancer or cancer treatment
  • Active heart or respiratory failure
  • Acute medical illness
  • Age over 60 years
  • Antiphospholipid syndrome
  • Behcet’s disease
  • Central venous catheter in situ
  • Continuous travel of >3 hours approximately 4 weeks before or after surgery
  • Immobility (for example, paralysis or limb in plaster)
  • Inflammatory bowel disease (for example, Crohn’s disease or ulcerative colitis)
  • Myeloproliferative diseases
  • Nephrotic syndrome
  • Obesity (body mass index ?30 kg/m2)
  • Paraproteinaemia
  • Paroxysmal nocturnal haemoglobinuria
  • Personal or family history of VTE
  • Pregnancy or puerperium
  • Recent myocardial infarction or stroke
  • Severe infection
  • Use of oral contraceptives or hormonal replacement therapy
  • Varicose veins with associated phlebitis
  • Inherited thrombophilias, for example:
      • high levels of coagulation factors (for example, Factor VIII)
      • hyperhomocysteinaemia
      • low activated protein C resistance (for example, Factor V Leiden)
      • protein C, S and antithrombin deficiencies
      • prothrombin 2021A gene mutation
 

VTE=venous thromboembolism
National Institute for Health and Care Excellence (NICE) (2007) CG 46 Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. London: NICE. Reproduced with permission.
Available from www.nice.org.uk.

Implications for primary care

The important recommendation in the guideline with respect to primary care is that daily subcutaneous injections of LMWH or fondaparinux prophylaxis should be routinely continued for 4 weeks after hip replacement and hip fracture surgery, where there is one or more patient-related risk factor (as listed in Box 1). This advice was not specifically listed for other orthopaedic procedures with a high incidence of VTE, particularly knee-replacement surgery, ankle surgery, and major trauma to the pelvis and lower limbs, but may need to be considered for patients who have undergone those procedures.

Hip replacement surgery

Deep vein thrombosis (DVT), which is diagnosed using contrast venography, occurs in up to 20% of patients who have undergone hip replacement surgery, even after routine treatment for 5–11 days with LMWH.3,4 The absolute rate of symptomatic VTE in these patients is about 3–5%, symptomatic pulmonary embolism (PE) 1%, and fatal PE 0.2–0.4%.5 The usual peak incidence of post-operative VTE occurs 5–11 days after surgery, which follows the maximum time of thrombin generation that occurs during surgery. However there is a second increased peak of VTE 1–2 weeks after the patient has been discharged home, and this is probably associated with prolonged immobility and venous stasis.6

It is now accepted that the risk of symptomatic clinical DVT and also that of fatal and major PE can be further reduced by continuing treatment with LMWH and fondaparinux for a month after surgery. At present most patients do not continue LMWH prophylaxis after discharge from hospital. As the duration of hospital stay is continually falling and is now about 4–6 days, only a few patients receive even the minimum 5–11 days of treatment.

Many orthopaedic surgeons previously prescribed low-dose oral aspirin on discharge, but this has now been shown to be largely ineffective and increases the rate of post-operative bleeding episodes. For these reasons NICE does not recommend aspirin as a method of prophylaxis.2

Post-discharge therapy

Prior to the operation, hospital healthcare professionals in the UK are now required to give patients verbal and written information 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.1,2 NICE has produced a booklet, Reducing the risk of a blood clot from surgery, which is for use by patients.

Following discharge home from hospital, the recommended policy of long-term (up to 4 weeks) LMWH prophylaxis, which has to be given by subcutaneous injection once to twice daily, will have significant implications on general practice time and resources.2 Many patients undergoing hip surgery are elderly and it may not be possible to teach them to inject themselves or there may not be a carer readily available on a daily basis to fulfil this task. These patients will need to be visited by the community nurse or cared for in a convalescent home.

Compression stockings

The guideline from NICE recommends the use of graduated compression stockings. The usual long-term post-surgical therapy will include using fitted graded compression stockings and the NICE guideline states that thigh-length stockings are more effective than those reaching to below the knee.2 However the guideline does allow for using these shorter stockings in the case of difficulties in compliance or fit.

Although compression stockings reduce the incidence of asymptomatic calf vein thrombosis and proximal thigh vein thrombosis, and therefore lessen the incidence of post-phlebitic limb syndrome, they do not reduce the incidence of major or fatal PE.

Unfortunately, compliance and documentation of daily stocking use is very poor, and after discharge home there is often a requirement to amend the correct size of stocking as a result of changes in leg circumference. Ideally the compression stockings should continue to be worn until the patient returns to his or her usual level of mobility.1,2 In addition, the guideline advises that healthcare professionals should encourage patients to mobilise as soon as possible after surgery.1,2

Heparin-induced thrombocytopenia

Patients who have undergone hip replacement therapy and who are receiving prophylaxis with LMWH are at risk of developing heparin-induced thrombocytopenia (HIT), which has an associated 40–50% risk of development, paradoxically, of venous or arterial thrombosis.7 The British Committee for Standards in Haematology recommends that platelet counts should be performed for all at-risk patients every 2–4 days from day 4 to day 14 of LMWH prophylaxis.7 If the platelet count falls by 50% or more, or if it falls below the laboratory normal range and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration, a diagnosis of HIT should be considered. A full clinical assessment should be carried out and treatment with LMWH should be stopped and other means of anticoagulant therapy initiated.

As patients after hip replacement surgery are generally discharged home around day 6 after surgery, they will therefore require one or two further platelet counts before they have received heparin for 14 days, by which time, if none of the clinical features of HIT have developed, the risk of it occurring is virtually eliminated. This represents a logistical nightmare for general practice. Primary healthcare professionals would, theoretically, be responsible for measuring the platelet count and comparing it to the pre-operative or immediate post-operative platelet count to see whether there has been a drop of 50% or more. How this is done will vary according to the local GP facilities. Usually the GP will send the blood sample to the local hospital laboratory.

The incidence of the development of HIT in patients receiving LMWH is probably only 0.5–0.8%.7 However, although the risk is relatively small, if HIT develops, thrombosis, which occurs in approximately 40–50% of these patients,7 may be extensive and potentially life threatening. Therefore, many doctors and healthcare professionals in primary care will have difficulty in fulfilling these requirements due to the time pressures of organising the blood count and checking the result.

Upcoming therapies

Within the next 12 months, new licensed preparations are expected to become available that are oral direct inhibitors of either thrombin (dabigatran) or factor Xa (rivaroxaban). These should be suitable for long-term prophylaxis of VTE, do not require laboratory monitoring, and, apparently, do not carry the risk of patients developing HIT with associated thrombosis.8 These oral, fixed-dose compounds will obviously be much easier to administer than daily subcutaneous injections of LMWH. However, there are costing implications of prescribing such oral treatment for 28 days after surgery, as they will undoubtedly be more expensive than LMWH prophylaxis.

Heparin therapy for other surgical procedures

In addition to use after hip replacement and hip fracture surgery, there is some evidence that extended heparin prophylaxis, as outlined above, may also be indicated in other post-surgical orthopaedic procedures. In particular, it may be suggested for patients with multiple associated risk factors. These include the following patients:

  • the elderly
  • those who are overweight
  • individuals who are relatively immobile after discharge home
  • those who have associated medical or known thrombophilia conditions (present in approximately 10–15% of the UK population) that would further predispose them to develop VTE after post-surgical discharge home. Similar problems will obviously apply to other major surgical procedures.

Uptake and implementation of the guideline

There is now recognition by the Government and the Department of Health of the need to reduce the incidence of VTE following major surgery.9 To reduce the burden of thrombotic disease, particularly following high-risk orthopaedic surgery, it is essential that the primary care team becomes involved when a patient is discharged from hospital. In order to achieve this, continual assessment and implementation of the guideline is needed. Unfortunately, at present it is difficult for primary care to implement the recommendations, and the guideline is apparently proving to have a relatively low uptake.

Further updates from NICE and the American College of Chest Physicians are expected in the near future, and the practicality and uptake of their recommendations need to be carefully considered.

 

  • NICE guidance on VTE places a heavy burden on primary care
  • As yet this guidance is hard for primary care to implement
  • PBC commissioners will need to develop a care pathway with secondary care clinicians and community nursing teams to effect implementation
  • Rapid, prompt, and accurate discharge information from secondary care, which is often lacking at present, will be essential
  • Agreement needs to be reached on who bears the cost of LMWH prophylaxis (e.g. is this part of the tariff price?)
  • LMWH heparin costs approximately £20/week for drug costs (NICE costing templatea) excluding administration costs
  1. National Institute for Health and Care Excellence. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. Clinical Guideline 46. London: NICE, 2007.
    www.nice.org.uk/CG046.
  2. National Collaborating Centre for Acute Care. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. London: Royal College of Surgeons of England, 2007.
  3. Geerts W, Pineo G, Heit J. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 Suppl): 338S–400S.
  4. Eriksson B, Dahl O, Rosencher N et al; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370 (9591): 949–956.
  5. Murray D, Britton A, Bulstrode C. Thromboprophylaxis and death after total hip replacement. J Bone Joint Surg Br 1996; 78 (6): 863–870.
  6. Planes A, Vochelle N, Darmon J et al. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348 (9022): 224–228.
  7. Keeling D, Davidson S, Watson H; Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The management of heparin-induced thrombocytopenia. Br J Haematol 2006; 133 (3): 259–269.
  8. Weitz J, Bates S. New anticoagulants. J Thromb Haemost 2005; 3 (8): 1843–1853.
  9. Department of Health. Report of the independent expert working group on the prevention of venous thromboembolism in hospitalised patients. A report to Sir Liam Donaldson Chief Medical Officer. London: DH, 2007.G