An Update on Venous Thromboembolism Prophylaxis in Hospitalised Patients

Britney Lergessner, Epic Pharmacy Northern Beaches

Introduction

Hospital associated venous thromboembolism (HA-VTE) represents a significant danger to hospitalised patients, occurring in 9.7 per 1,000 admissions in Australia at a rate that is 100 times higher than among the Australian general population.1, 2 It is estimated to cost the Australian Health System $1.72 billion annually.3-5 Mortality from HA-VTE is estimated to be as high as 1 in 10 and account for 7% of all deaths in Australian hospitals despite being the leading cause of preventable deaths.

There has been significant progress over the past decade with reductions in rates of VTE in Australia with a new clinical care standard released in 2020.6,7

Risk Assessment and contraindications to prophylaxis

Hospital inpatients commonly have significant risk factors for VTE but also for bleeding, especially in critically ill patients.8, 9 Assessing VTE risk is challenging and has led to numerous VTE Risk Assessment Tools designed to predict VTE risk during hospitalisation.

The ‘IMPROVE’ and ‘Geneva’ risk score are the preferred tools by clinicians.9, 10 Patients with cancer, thrombophilia, pregnancy, and those who are critically unwell are at heightened risk of VTE and should be risk assessed accordingly.

Contraindications to chemical VTE prophylaxis include: patients with active bleeding, those planned for imminent surgery, those with moderate-tosevere coagulopathies and severe thrombocytopenia (< 50x109/L).11

Methods of VTE Prophylaxis

Patients who can mobilise early, i.e. within 24 hours and adhere to mechanical prophylaxis have been shown to have a lower risk of VTE. Mechanical VTE includes intermittent pneumatic compression (SCUDS – Sequential Compression Devices), venous foot pumps, and thigh or knee-length graduated compression stockings (TEDS - Thrombo-Embolus Deterrent Stockings). While they are considered relatively safe, the efficacy of mechanical compression is less than anticoagulation.6 Mechanical prophylaxis is also employed among patients in whom anticoagulation is contraindicated. The commonly used evidence-based pharmacological treatments are low molecular weight heparin (LMWH) eg. enoxaparin and unfractionated heparin (UFH). Some data suggests LMWH is superior to UFH in regard to both reduction in VTE and bleeding rates.12, 13 Platelet count should be monitored regularly during treatment for prevention or early intervention of Heparin Induced Thrombocytopenia Syndrome (HITS) (Table 1). If left untreated, HITS can lead to thrombosis in up to 50% of patients with a mortality rate of 5-10%.14

Subcutaneous dosing for enoxaparin is 40mg daily which can be reduced to 20mg daily in renal impairment, and for UFH 5,000 units twice daily. While there is limited evidence on dosing in obesity, the American College of Chest Physicians recommend weight based dosing of 0.5mg/kg for patients with a BMI >40kg/m2 and the International Society on Thrombosis and Haemostasis suggests that rivaroxaban or apixaban can be considered in this population.16, 17

Rivaroxaban 10mg daily presents an alternative oral anticoagulation option and together with fondaparinux 2.5mg daily has evidence to suggest it is non-inferior to LMWH or UFH in acute medical inpatients, though with limited comparative evidence to LMWH/UFH, it is rarely used.18, 19 Currently, only rivaroxaban, apixaban and fondaparinux is PBS approved as VTE prophylaxis for patients undergoing total hip or knee replacement. Duration of anticoagulation is typically restricted to length of hospitalisation as extended duration is associated with increased bleeding without changing rates of VTE.20, 21

There is substantial evidence to suggest that aspirin should not be used as VTE prophylaxis.22 This was best demonstrated in the ‘CRISTAL’ trial, an Australian multicentre study of patients undergoing hip or knee arthroplasty which demonstrated inferiority of aspirin compared to LMWH

(Figure 1).23 Despite this, an Australian national survey of orthopaedic surgeons suggested that over 50% use aspirin as part of the VTE prophylaxis strategy.7 There is, however, evidence that low dose aspirin daily can be used as extended thromboprophylaxis after an initial 5-10 day course of anticoagulation.24

Special Populations

Some patient populations require a more tailored approach to anticoagulation. The most common of these is patients with severe renal failure in whom UFH would be preferred over LMWH, or those with morbid obesity in which a dose increase may be required, though the evidence to support this is currently limited. In patients with extreme obesity it may be reasonable to monitor serum Anti-Xa levels which can predict dosing efficacy.25 Patients with evidence of HITS are recommended treatment with danaparoid, bivalirudin or fondaparinux.

Among patients with severe renal impairment argatroban is a suitable alternative though availability is limited.

Conclusion

Australian guidelines reinforce the importance not just of pharmacological prophylaxis but of mechanical prophylaxis, early ambulation, adequate hydration and partnering with patients/carers.6

Partnering with patients with the goal to improve compliance and achieve earlier ambulation has shown to significantly reduce post-operative VTE.27

Research has shown the successful implementation of alerts, doctorpharmacist collaborative approaches and nurse-led interventions to improve adherence.28-30 Solid evidence supports the effectiveness of a multidisciplinary approach from health professionals to reduce rates of VTE and VTE-related mortality and morbidity.

Interpretation:

≤3 points: low probability for HIT (≤5% in original study)

4-5 points: intermediate probability (~14% probability of HIT)

6-8 points: high probability (~64% probability of HIT)