Introduction
VTE risk assessment
Risk of bleeding
Modes of prophylaxis
Patient information
Pharmacological prophylaxis
Mechanical prophylaxis
Medical patients
Surgical patients
Orthopaedic patients
Discharge planning
Governance
Conclusion
References


Introduction

Venous thromboembolism (VTE) is an important cause of mortality for hospital in-patients.1,2,3 Clinicians are required to assess for the risk of VTE and bleeding on admission and then prescribe appropriate prophylaxis.1,3 Following this initial assessment, the risk of VTE and bleeding needs to be reassessed. Many patients may be discharged from hospital with a plan to continue VTE prophylaxis in the community; therefore, VTE prophylaxis is of importance in both hospital and community settings. 

VTE risk assessment

All patients admitted to hospital require an assessment of the risk of venous thromboembolism and the risk of bleeding complications.4 This includes short duration hospital admissions, for example, day surgery. Risk factors for VTE include age greater than 60 years,2 medical comorbidities, acute surgical admission, cancer and immobility.(Box 1) Clinicians need to complete this assessment and then prescribe and administer appropriate VTE prophylaxis.

Box 1 Risk factors for VTE

  • Age greater than 60
  • Active cancer or cancer treatment
  • Dehydration
  • Obesity
  • Personal history or first degree relative with a history of DVT
  • Significantly reduced mobility for three days or more
  • Hip or knee replacement
  • Hip fracture
  • Critical care admission
  • Surgery: total anaesthetic time and surgical time >90 minutes
  • Surgery involving pelvis or lower limb with a total anaesthetic + surgical time >60 minutes

In view of the importance of VTE risk assessments, NHS England is collecting data from hospital trusts regarding the percentage of patients that have VTE risk assessment on admission. Trusts have introduced various measures to improve the rate of VTE risk assessments. This includes reminder emails to clinicians, posters, nursing staff reminding trainee doctors and champions.6 With the increasing use of electronic prescribing, it is possible to send an alert to the clinical teams if VTE assessment has not been completed.7

Following admission, the VTE risk assessment should be completed as soon as possible. Thereafter, VTE reassessment should be undertaken on subsequent consultant ward rounds or if clinical condition changes.1 The importance of reassessment may be illustrated by this example. A patient is admitted with a suspected upper GI bleed therefore pharmacological prophylaxis is omitted. Following reassessment a few days later the consultant balances risk of VTE with risk of bleeding; consequently, pharmacological prophylaxis is restarted.

Risk of bleeding

Thrombocytopenia and bleeding diathesis are risk factors for bleeding (box 2). Thrombocytopenia may be due to drugs or sepsis; thereby pharmacological prophylaxis may be cautioned. However, if the platelet count returns to acceptable levels, prophylactic LMW heparin may be commenced. This further illustrates the importance of reassessment of VTE and bleeding risk on ward rounds.

Box 2 Risks of bleeding

  • Active bleeding
  • Thrombocytopaenia (platelets <75x109/l)
  • Acquired and inherited bleeding disorders
  • Concurrent use of anticoagulants, for example warfarin (with INR greater than 2) or
  • Direct Acting Oral anticoagulants (DOACs)
  • Uncontrolled hypertension

Patients may be taking oral anticoagulates pre-admission for reasons including atrial fibrillation, mechanical heart valve or prior VTE. For such patients there is usually no need for prescribing additional pharmacological prophylaxis as bleeding risk will increase. However, anticoagulation may be interrupted for several reasons. For example, consider a patient with Parkinson’s disease and atrial fibrillation (AF) that is usually taking a DOAC. If the patient develops aspiration pneumonia oral anticoagulation may need to be omitted. For such patients, bridging anticoagulation with LMW heparin may be considered. For patients taking warfarin, bridging therapy with LMW heparin may be considered if INR is subtherapeutic.

Patient information

It is important to discuss the risk and benefits of VTE prophylaxis to the patient and carers. Many of our patients may lack mental capacity due to dementia or delirium; therefore, decisions need to be taken in best interest. Information may be provided verbally or in writing; in-patient information leaflets are provided to patients.

Modes of prophylaxis

Virchow’s Triad describes the pathological processes involved in development of VTE; that is vascular endothelial damage, stasis of blood flow and hypercoagulability.8 The agents used in VTE prophylaxis act by reducing the impact of one or more of these processes.

General considerations

Early mobilisation and adequate hydration reduce the risk of VTE.13 For example, following hip fracture surgery or stroke, patients require mobilisation as soon as possibly by the rehabilitation team. On ward rounds doctors should view the fluid balance charts and ensure patients are receiving appropriate hydration.

Pharmacological prophylaxis

Aspirin

There is evidence that aspirin reduces the risk of VTE however this is not recommended as a sole agent in prophylaxis.3

Heparin

Low molecular weight heparin is preferable compared to unfractionated heparin due to more robust evidence, lower risk of bleeding3 and lower risk of heparin induced thrombocytopenia. An example of LMW heparin used for the purpose of prophylaxis in medical patients is enoxaparin 40mg subcutaneously once a day. In other hospital trusts, tinzaparin and dalteparin are used.

Fondaparinex

The synthetic pentasaccharide fondaparinux is a highly selective, indirect inhibitor of factor Xa. It is licensed for use in prophylaxis of VTE if for patient is intolerant of LMW heparin.1

Mechanical prophylaxis

Intermittent pneumatic compression device (IPCD)

In addition to improvement of venous return, IPCD have been shown to increase fibrinolytic activity.9 Poor compliance rates may be related to patients reporting discomfort in wearing the device.8,10 Moreover, some devices require an external power source therefore limiting patient mobility; this is a cause for concern for patients that require mobilisation.10 Battery operated devices are available; however, these are not in widespread use.10 Units may have insufficient or poorly functioning devices10 limiting usage. The main contraindication to IPCs is allergy to the sleeves.11

Anti-embolic stockings (AES)

AES increase blood flow in the venous circulation thereby reducing venous stasis (SIGN). In a cochrane review, AES decrease risk of DVT in orthopaedic and general surgical patients.13 AES offer advantages compared to pharmacological prophylaxis for example lack of risk of bleeding. Disadvantages of AES include difficulties in applying the stockings and pain and discomfort.11 This may lead to suboptimal compliance or patients declining their application.11 Adverse effects of AES include blistering, skin discolouration, allergic reactions and abrasions.11

There are several cautions in use of AES for example severe leg oedema, leg deformity, dermatitis, fragile skin, peripheral vascular disease or peripheral neuropathy.1 Clinicians should assess for the presence of peripheral pulses and integrity of the skin before applying AES.

On ward rounds, clinicians need to ensure the VTE prophylaxis has been administered by nursing staff. It is important to ascertain reasons for patients declining AES; for example, patients may state that AES are uncomfortable or complain of bruising at the injection site of LMW heparin. The ward round is an ideal opportunity to discuss concerns with the patient.1 Patients concerned about risk of bruising and bleeding may be reassured once the risks and benefits are explained. 

Medical patients

For acutely ill medical patients prophylactic LMW heparin and unfractionated heparin reduces risk of VTE. LMW heparins are renally excreted and are therefore cautioned in renal impairment. If creatinine clearance is between 15 and 30ml/min then reduction of the dose to 20mg once a day is recommended.15 If creatinine clearance is less than 15ml/hour, enoxaparin is not recommended; in such situations, unfractionated heparin at dose of 5000units twice a day should be considered.15

Renal function may fluctuate during a hospital stay. For example, if a patient is admitted with community acquired pneumonia and creatinine clearance of 20ml/hour then the 20mg dose of enoxaparin is recommended.15 However, if creatinine clearance improves to 50ml/hour then the dose may be increased to 40mg once a day.  This underscores the importance of reassessment of the risk of VTE and bleeding whilst on the ward round. Patients with low body weight (woman <45 kg; men <57kg) usually require a reduction of the dose to 20mg sc once a day.15

A frequently asked question is duration of prophylaxis in medical patients. In fact, there is no evidence of benefit beyond 7-14 days.11,14 Therefore, clinicians need to use clinical judgement if pharmacological prophylaxis is administered beyond 14 days.

In the past, AES were to be considered if there were contraindications to LMW heparins. However, in view of the risks of use of AES as described above, and the lack of evidence supporting AES,1,3,13 the current NICE guidelines does not support the use of AES in medical patient. The attending physician may decide to administer AES based upon clinical judgement taking risks and benefits into account (NICE).

Surgical patients

General considerations

Regional anaesthesia carries less risk of VTE compared to general anaesthesia; for example nerve block or epidural anaesthesia may be considered following discussion of risks and benefits with the patient.1 Four weeks before elective surgery, patients are advised to stop oestrogen containing medication.1

Orthopaedic patients

Orthopaedic patients are at high risk of VTE.8 The mode and duration of VTE prophylaxis does differ depending on the nature of the surgery.

Elective hip replacement

Orthogeriatricians work in collaboration with orthopaedic surgeons in caring for elderly patients. It is acknowledged that patients with fractured neck of femur are cared for by a MDT, with input from geriatrician and therapy staff.17 VTE risk assessment is included in fractured neck of femur pathways.18 For patients undergoing surgery for neck of femur or pelvic fracture, prophylactic LMW heparin should be administered 6-12 hours following surgery.1

IPCs reduce risk of VTE10 following hip fracture surgery (HFS) and may be applied if patients have contraindications to LMW heparin.10 NICE11 does not recommend AES for patients following fractured neck of femur due to lack of evidence and risks of applying the stockings. Despite the recommendation from NICE, many orthopaedic wards in the region do not apply IPCs; this is mainly due to lack of availability of devices (personal discussion with neighbouring units).10 

Elective hip replacement

There are several options for VTE prophylaxis. There is evidence that extended prophylaxis reduces the risk of VTE19 therefore guidelines suggest a course of LMW heparin for 28 days or longer.8,10 Moreover, AES are recommended in combination with AES until discharge. Other measures used for VTE prophylaxis are LMW heparin for 10 days followed by aspirin for a further 28 days or rivaroxaban.20

Elective knee replacement

NICE describes three options for VTE prophylaxis. Aspirin for 14 days, LMW heparin for 14 days and AES until discharge or Rivaroxaban.1

Abdominal surgery

For patients at risk of VTE, undergoing abdominal surgery, AES or IPCD is recommended. The surgeon is required to balance the risk of bleeding and risk of VTE before prescribing pharmacological prophylaxis. For cancer surgery, consider continued prophylaxis for 28 days (NICE).

Critical care/trauma

For patients admitted to critical care with major trauma, IPCD should be considered.1 In contrast to some medical and surgical wards, IPCD are readily available in critical care units (personal observation/discussion with neighbouring Trusts). For patients with traumatic brain injury, there is concern that LMW heparin may cause extension of intracranial haemorrhage. The risk of VTE and bleeding should be reviewed on a daily basis; LMW heparin may be prescribed once the risk of bleeding is reduced. The optimal timing of initiation of pharmacological prophylaxis is debated; however, studies indicate that initiation within 72 hours may be safe.21

Acute stroke

The incidence of stroke rises with age. Previous trials have shown no evidence of benefit with AES; however, the CLOTS 3 trial showed that intermittent pneumatic devises 23 reduced the incidence of DVT.22 As a result of this data, the Royal College of Physicians recommend IPCD for patients that are unable to mobilise to the toilet without the help of another person.23 Ideally, IPCDs should be applied within three days of admission and usually be continued for 30 days unless patient is discharged, or mobility is restored.

For patients with ischaemic stroke, LMW heparin may be used as a prophylactic agent; however, there is a risk of haemorrhagic transformation of the infarct. Stroke physicians should balance risk of VTE and bleeding before prescribing LMW heparin. 

Discharge planning

As stated above, VTE prophylaxis may continue after discharge. It is necessary for clinicians to include instructions on the discharge summary for primary care and community services. Many of our patients may have difficulty in self administration of LMW heparin and application of AES due to cognitive impairment or physical disabilities. Therefore, ward staff need to ensure provision and training of caregivers. As an example, caregivers may need training to inspect the skin for abrasions in patients wearing AES. Patients and caregivers need to be provided with contact numbers in case of queries or difficulties.1

Governance

NICE1 does provide an audit tool. Clinical audit standards include VTE and bleeding risk assessment on admission, reassessment by consultant and appropriate administration of pharmacological and mechanical prophylaxis.

If there are concerns regarding VTE prophylaxis, it is important to alert patient safety; hospital trusts usually have Patient Safety Incident Management system. A root cause analysis may be undertaken; learning points are disseminated to clinicians.

Conclusion

Clinicians do need to realise the importance in VTE prophylaxis for our patients. Prescription and application of VTE prophylaxis may prevent your patient developing a VTE. The examples in this article highlight the importance in assessment and reassessment of the risk of VTE and bleeding; VTE prophylaxis may be adjusted following review by clinicians. Balancing the risk of VTE and bleeding is, at times, difficult; therefore, advice from a senior doctor may be needed.

Authors

Dr Elliot Epstein, Consultant Physician in elderly care, Manor Hospital, Walsall

Dr Korah Shalan, Consultant Physician, Manor Hospital, Walsall

References

1. NICE Venous thromboembolism over 16s: reducing the risk of hospital-acquired reducing the risk of hospital-acquired deep vein thrombosis or pulmonary vein thrombosis. NICE; 2018 nice.org.uk/guidance/ng89

2. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14. doi:10.1007/s11239-015-1311-6

3. Scottish Intercollegiate Guidelines Network (SIGN). Prevention and management of venous thromboembolism. Edinburgh: SIGN; 2010. (SIGN publication no. 122). Accessed May 2019. Available from URL: http://www.sign.ac.uk

4. Department of Health. Risk assessment for Venous thromboembolism. DOH; 2010. Last accessed June 2019. Available from: https://www.nice.org.uk/guidance/ng89/resources/department-of-health-vte-risk-assessment-tool-pdf-4787149213

5. NHS England Venous Thromboembolism (VTE) Risk Assessment NHS England. England: 2018 https://www.england.nhs.uk/statistics/statistical-work-areas/vte/

6. Watts L, Grant D. Venous thromboembolism (VTE) risk assessment and prophylaxis in acute orthopaedic admissions: improving compliance with national guidelines. BMJ Open Quality 2013;2:u202229.w1118. doi: 10.1136/bmjquality.u202229.w1118

7. Nwulu U, Brooks H, Richardson S, McFarland L, Coleman J. Electronic risk assessment for venous thromboembolism: investigating physicians' rationale for bypassing clinical decision support recommendations. BMJ Open 2014; 4(9)

8. Flevas D, Megaloikonomos P, Dimopoulos L, et al. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev 2018;3: 130-142

9. Comerota A. The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis. Ann Surg. 1997; 226(3): 306–314

10. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S–e325S. doi:10.1378/chest.11-2404

11. NICE Venous thromboembolism in over 16s. Methods, evidence and recommendation. NICE; 2018

13. Sachdeva  A, Dalton  M, Lees  T. Graduated compression stockings for prevention of deep vein thrombosis. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD001484. DOI: 10.1002/14651858.CD001484.pub4

14. Samama, M Cohen A, Darmon, J et al.  Comparison of Enoxaparin with Placebo for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patient. N Engl J Med 1999; 341:793-800

15. EMC. AROVI 10,000 IU (100mg/1ml) pre-filled syringe with safety device https://www.medicines.org.uk/emc/product/9329/smpc#PHARMACOKINETIC_PROPS

16. NICE

17. NICE Hip fracture: management NICE 2017https://www.nice.org.uk/guidance/cg124/chapter/Recommendations

18. Walsall NHS Trust. Fractured neck of femur pathway. Walsall NHS Trust: Walsall; 2018

19. Hull RD, Pineo GF, Stein PD, et al. Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty: A Systematic Review. Ann Intern Med. 2001;135:858–869. doi: 10.7326/0003-4819-135-10-200111200-00006

20. Eriksson B, Borris L, Friedman R, Haas S, Huisman M. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Hip Arthroplasty N Engl J Med 2008; 358:2765-2775 DOI: 10.1056/NEJMoa0800374

21. Byrne J, Mason S, Gomez D, et al. Timing of Pharmacologic Venous Thromboembolism Prophylaxis in Severe Traumatic Brain Injury: A Propensity-Matched Cohort Study Journal of the American College of Surgeons. 223, Issue 4, 2016 223 (4)  621-631.e5

22. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial Lancet 382, 516-524, 2013

23. Royal College of Physicians. National Clinical Guidelines for Stroke Fifth Edition RCP: London. 2016