What are the risk factors?
Risk factors can be divided into three types: increased stasis, reducing venous circulation; hypercoagulable states that alter normal blood haemostasis; and trauma to tissue or blood vessels causing coagulation and thrombus formation.
What can patients do before hospital admission?
Patients who are obese should try to reach a healthy BMI before an elective hospital admission. Women on the combined oral contraceptive pill or HRT should stop therapy four weeks before surgery.
What can community pharmacists do?
Pharmacists should familiarise themselves with VTE prevention and treatment, and ask local hospitals for a copy of their policies. Recently discharged patients who are prescribed VTE prophylaxis should receive an MUR to ensure the risk of VTE is minimised.
Venous thrombosis is a condition where a blood clot (thrombus) forms in a vein. The clot may restrict blood flow through the affected vein, giving rise to swelling and pain, or may be asymptomatic.
The most common sites for thrombus formation are the deep veins within muscle, typically of the calf or the thigh. This is known as deep vein thrombosis (DVT).
The thrombus may dislodge and travel in the blood to the lung, which is known as pulmonary embolism (PE). Collectively, DVT and PE are known as venous thromboembolism (VTE).
A survey performed in two hospitals in 2005 found 71 per cent of patients who were assessed to be at moderate to high risk of VTE did not receive VTE prophylaxis.1 It was estimated that VTE caused in excess of 25,000 preventable hospital deaths each year in the UK.2
Documented risk assessment and subsequent appropriate thromboprophylaxis to prevent an occurrence of VTE is likely to reduce morbidity associated with long-term vascular effects and mortality, as well as lead to cost savings, primarily due to the reduced need for hospital readmissions.
Causes and risk factors
There are multiple causes and risk factors for DVT. Excessive stasis of the venous circulation is a risk factor for the formation of clots. General anaesthesia, prolonged immobility and some medical conditions such as malignancy and heart disease can increase stasis. Surgery and some medical conditions, such as cancer and some chronic inflammatory conditions, can produce a response that results in hypercoagulable states that alter normal blood haemostasis systems. Trauma to tissue or blood vessel walls can expose blood to tissue factor, triggering the coagulation cascade and thrombus formation. Any one of these three factors, known as Virchow’s triad, increases the risk of formation of a thrombus.
While the risk of developing DVT is as high as 45-51 per cent in patients undergoing orthopaedic surgery if they are not provided with thromboprophylaxis, the majority of hospitalised patients who experience VTE are medical patients, primarily due to immobilisation. Current guidelines therefore recommend VTE risk assessment for all patients admitted to hospital.4
Some patient-related risk factors, such as a high BMI, are part of the vascular risk assessment conducted by community pharmacists. Helping patients who are obese achieve a healthy BMI before an elective hospital admission can reduce the individual’s risk of developing VTE.
Nice advises temporarily stopping the combined oral contraceptive pill or HRT four weeks before surgery. Aspirin and other antiplatelet drugs do not offer sufficient protection against a possible DVT, and may increase the risk of bleeding during surgery.
Five treatment options
Patients in hospital who are deemed to be at risk of VTE may be offered anti-embolism stockings or an intermittent pneumatic compression device to help keep the blood in their legs circulating. They may also be prescribed pharmacological thromboprophylaxis to prevent blood clots forming.
Before being offered any of these, patients should be given advice and a leaflet on the risks of DVT, what might happen if they develop DVT, how to use stockings or devices to help prevent DVT and how they can reduce their risk of DVT (eg hydration and, if possible, exercising).
Heparin acts as an anticoagulant by binding and accelerating the action of antithrombin, a naturally occurring inhibitor of thrombin and other coagulation enzymes. It is administered by continuous or intermittent intravenous infusion or subcutaneous injection. Heparin can bind to circulating proteins, forming a complex that has the potential to induce thrombus formation and ischaemia. This is referred to as heparin-induced thrombocytopenia (HIT) and is a serious complication of heparin therapy, which may result in amputation or death.
Several preparations of low molecular weight heparin (LMWH) are available that bind less avidly to other heparin binding proteins and therefore have a more predictable dose response and greater safety, due to a lower incidence of HIT, than unfractionated heparin. LMWHs are administered subcutaneously once or twice daily. LMWH may be used in patients at high risk of VTE, usually starting six hours post-operatively. For some patients, LMWH may be administered after discharge by the patient, following training, or by a community nurse. Arrangements for sharps disposal must be provided prior to discharge. Dalteparin, enoxaparin and tinzaparin are all LMWHs.
2. Factor Xa inhibitors
Factor Xa inhibitors fall into two main categories: direct or indirect. Fondaparinux is an indirect Factor Xa inhibitor. It acts by potentiating the antithrombin inhibition of Factor Xa. It has a long half-life (17 hours), which allows for once-daily dosing and is administered subcutaneously. Bleeding is a potential side effect. Fondaparinux is contraindicated in patients with creatinine clearance <30ml/min. It is licensed for prevention of VTE in a range of adult patients. Protamine may be administered to reverse its effects.
Rivaroxaban is a direct Factor Xa inhibitor, which may be administered orally. Inhibition of Factor Xa interrupts both thrombin formation and development of thrombi. Rivaroxaban must be used with caution in patients with renal impairment and is contraindicated in patients with a creatinine clearance of <15ml/min. It is also contraindicated in patients taking ketoconazole, itraconazole, ritonavir and rifampicin. Current Nice guidelines recommend rivaroxaban for patients undergoing hip or knee replacement, with a duration of 28-35 days for hip fracture or replacement and 10-14 days for patients after knee replacement. Data on long-term safety is pending.
Dabigatran is a potent reversible direct thrombin inhibitor. After oral administration, dabigatran exilate is rapidly absorbed and converted to dabigatran in the plasma and liver. It acts on Factor 11a to inhibit the conversion of fibrinogen to fibrin and inhibits free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregration. It should be used with caution in patients with renal impairment and is contraindicated in patients with a creatinine clearance of <15ml/min. The dose is adjusted downwards for patients over 75 years, or patients with a creatinine clearance of 30-50ml/min. Dose adjustment is required for patients taking amiodarone or verapamil. It is contraindicated in patients taking quinidine, ketoconazole or rifampicin. Some patients taking dabigatran may develop symptoms of gastric irritation and should be advised this generally resolves without the need to stop treatment, and may be avoided by taking the medicine with food. Nice recommends dabigatran etexilate as an option for VTE prophylaxis after total hip or knee replacement surgery. Data on long-term safety is pending.
Warfarin is a coumarin derivative and vitamin K antagonist. It is administered orally at adjusted variable doses to achieve a therapeutic level as estimated by an international normalised ratio (INR) specific to the patient’s condition. It has significant potential for drug-drug, drug-food and drug-disease interactions and therefore requires therapeutic monitoring. Some patients may be converted to warfarin dosing and monitored in the community or in hospital outpatient settings.
Manufacturers advise caution when using rivaroxaban or dabigatran with non-steroidal anti-inflammatory drugs (NSAIDs) because of a potentially increased risk of bleeding, but the combination is not contraindicated. Local guidelines for rivaroxaban, such as those developed at University College London Hospital, recommend avoiding the use of NSAIDs for post-operative analgesia where possible. However, where use of an NSAID is essential, a drug with a shorter half-life and reduced gastrointestinal and cardiovascular side effect profile should be used, such as ibuprofen. Routine gastrointestinal prophylaxis with a proton pump inhibitor or ranitidine is not warranted unless the patient is at high risk from NSAID therapy.6
Community pharmacists can help patients reduce their risk of VTE by providing MURs for patients following hospital discharge. To provide this service, it will be necessary to be familiar with aspects of VTE prevention and treatment and have access to local hospital policies for VTE prevention. Private hospitals may also have different VTE prevention policies.
Post-discharge care can include advising on skin care for patients with anti-embolism stockings, or who experience discomfort or develop an allergic reaction to the material of manufacture and ensuring concordance with thromboprophylaxis regimens for patients discharged on medications. Knowing when to refer patients for assessment and urgent monitoring by other members of the healthcare team is also key. It is useful to reinforce the information provided to patients in written information leaflets about the importance of avoiding dehydration and encouraging exercise.
For key facts about VTE, further reading and references, see the full version of this article atwww.chemistanddruggist.co.uk/update
Doreen Cochrane is an independent clinical pharmacist and has provided anticoagulation clinics in primary care
Download a CPD log sheet that helps you complete your CPD entry when you successfully complete the 5 Minute Test for this Update article online (details on p20).
Risk factors for VTE3
- Active cancer or cancer treatment
- Age over 60 years
- Critical care admission
- Known thrombophilias
- Obesity (BMI over 30kg/m2)
- One or more significant medical
- Personal history or first-degree relative
with a history of VTE
- Use of hormone replacement therapy
- Use of oestrogen-containing
- Varicose veins with phlebitis
- Women who are pregnant or have given birth within the previous six weeks
How can DVT present in community pharmacy?
A patient with DVT may present with symptoms of pain and swelling, changes in skin colour or temperature, vein distension at the skin surface, pitting oedema or tenderness. The most common clinical symptoms of PE are breathlessness, chest pain, and a cough. Tachycardia, tachypnoea or raised jugular venous pressure may occur, leading to the patient collapsing. Patients with suspected PE, and some patients at high risk for DVT, require urgent referral for same day assessment and management. The latter includes pregnant women and women who have given birth in the past six weeks.
Case Study: herbal preparations
A 50-year-old woman in a wheelchair enters the pharmacy. She explains she has had recent orthopaedic surgery and has been discharged with tinzaparin prescribed for 28 days. She used to work as a nurse and self-administers the dose subcutaneously. She would like advice about herbal hormone replacement treatments containing sage, which she had been using to prevent menopausal symptoms prior to her hospital admission.
How would you counsel the patient about the potential interaction of these treatments?
Due to lack of data the manufacturer cannot recommend concurrent use of herbal preparations and tinzaparin. Given the importance of compliance with DVT prophylaxis, the patient should be encouraged to complete the course of LMWH and re-start her herbal supplement about one day after her last dose of tinzaparin.
She would also like to know how to dispose of her sharps. What do you advise?
This depends if you have facilities in your pharmacy for disposal of a yellow bin. If you do not, you might advise her to return it to her general practice for disposal.
- Patient information leaflet on diagnosis and treatment www.thrombosis-charity.org.uk
- King’s Thrombosis Centre – patient and pharmacist information from exemplar siteswww.kingsthrobosiscentre.org.uk
- Interactive CPD resource for pharmacists www.linkupvte.com
1. Rashid S, Thursz M, Razvi N et al., Venous thromboembolism in UK medical inpatients. Journal of the Royal Society of Medicine 2005; 98: 507-12.
2. House of Commons Health Committee. The prevention of venous thromboembolism in hospitalised patients. London: The Stationary Office, 2005.
3. National Institute for Health and Clinical Excellence. Venous thromboembolism: reducing the risk-reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. Clinical Guideline 92. London NICE, 2010.
4. Department of Health. Venous thromboembolism (VTE) risk assessment. London: DH, 2010.
5. emc Summary of Product Characteristics for Fragmin, Clexane, Innohep, Arixtra, Xarelto, Pradaxa and warfarin. Accessed January, 2011.
6. Is it safe to prescribe NSAIDs with dabigatran etexilate and rivaroxaban? UKCPA (2010) Available atwww.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q–A/Is-it-safe-to-prescribe-NSAIDs-with-dabigatran-etexilate-and-rivaroxaban/
What are the risk factors for VTE? How are LMWHs administered? Which drugs interact with rivaroxaban? What are the side effects of dabigatran?
This article describes venous thromboembolism and includes information about causes, risk factors and symptoms. It also discusses the drugs used in prevention and treatment of VTE such as heparin, Factor Xa inhibitors, dabigatran and vitamin K agonists.
- Find out more about deep vein thrombosis and pulmonary embolism on the Patient UK website athttp://tinyurl.com/vte01 and http://tinyurl.com/vte01a.
- Revise your knowledge of the drugs used in VTE by reading section 2.8 Anticoagulants and protamine of the BNF.
- Think about the advice that you could give to patients who wear compression hosiery about compliance, aids for putting on stockings and skincare. Identify those who might benefit from an MUR.
- For further learning the CPPE has a programme on venous thromboembolism (ref 39960) available at www.cppe.ac.uk.
Are you now confident in your knowledge of VTE and its risk factors? Are you familiar with the drugs used in the treatment and prevention of VTE? Could you give advice to patients about compression hosiery and skincare?