The dilemma of thromboprophylaxis in stroke patients

Abstract

Acute stroke is one of the leading causes of mortality worldwide, with venous thromboembolism (VTE) representing a significant yet under-recognised complication. The risk of VTE is highest in the early post-stroke period, driven by factors encapsulated by Virchow’s triad. However, the risk of haemorrhagic transformation following ischaemic stroke, and haematoma development and expansion after haemorrhagic stroke complicate the routine use of pharmacological VTE prophylaxis. In this review, we discuss the epidemiology and aetiology of VTE post-stroke, haemorrhagic transformation after acute ischaemic events, and the available evidence supporting mechanical and pharmacological approaches to VTE prophylaxis in these patients. Finally, we discuss the recommendations provided by the current international consensus guidelines and reasons underpinning the heterogeneous management of patients in routine clinical practice, including the need for well-designed, large-scale clinical trials to better define thromboprophylaxis strategies for patients following acute stroke.

Graphical Abstract

Introduction

Worldwide, stroke was the third leading cause of mortality in 2021, accounting for around 7 million deaths.¹ The number of hospital admissions each year due to stroke is rising, and the age of presentation is falling, with a significant increase in cases under the age of 50 years noted.2, 3, 4 The majority of strokes are ischaemic in nature (approximately 65.3% globally as of 2025), and their rate is higher in higher-income countries, for example the USA where prevalence was 87%.5, 6 These are mostly caused by atherosclerosis and cardioembolic events, with the rising incidence attributable to an ageing population and increasing rates of cardiovascular risk factors such as hypertension, diabetes and obesity.⁷ Venous thromboembolism (VTE) is not an uncommon complication of stroke. However, guidelines regarding the use of thromboprophylaxis in this situation are not well defined. In this review, we consider the epidemiology of VTE post-stroke, the evidence for VTE prophylaxis and guideline recommendations, and provide practical suggestions for clinicians treating these patients.

Methods

PubMed and Google Scholar were utilised to identify relevant articles concerning the pathophysiology and incidence of VTE post-ischaemic and haemorrhagic stroke, and evidence supporting VTE prophylaxis post-stroke (randomised controlled trials and meta-analyses). The current American, British, Canadian and European guidelines on VTE prophylaxis were gathered from the respective national guidelines.

VTE post-ischaemic stroke

VTE is a common complication of ischaemic stroke. The risk of VTE may be up to 20-fold higher, compared to an age-matched healthy population during the initial month following an ischaemic stroke (HR 19.7, 95% CI 10.1–38.5), up to 10-fold higher during the first 3 months post-stroke (HR 10.6, 95% CI 5–22.5), and two-fold higher for the first year (RR 2.19, 95% CI 1.85–2.60).8, 9, 10 A Norwegian study found the incidence of stroke in the general population to be 1.43 per 1,000 (CI 1.33–1.54).¹¹ Without the use of heparin prophylaxis, the incidence of deep vein thrombosis (DVT), usually asymptomatic, below-knee DVT, is around 50% in the first 2 weeks following an acute stroke, with a peak incidence during days 2–7.12, 13 This risk persists into the rehabilitation phase, with DVT rates of one-third reported in patients admitted to a rehabilitation unit, on average 9 weeks post-stroke.¹⁴ The main risk posed by an asymptomatic DVT is that of a subsequent pulmonary embolism (PE). PEs tend to present after the first week of stroke and have been shown to contribute to 7–30% of mortality post-stroke.15, 16, 17 Non-fatal PEs can also cause significant morbidity, impacting on cardiorespiratory reserve and quality of life.¹⁸

Virchow’s triad, comprising damage to blood vessel endothelium, circulatory stasis and a hypercoagulable state, forms the foundation of thrombus formation in VTE.¹⁹ Risks for VTE post-stroke include immobilisation, infection, presence of indwelling lines, cancer, obesity, stroke severity, length of hospital stay and the requirement for rehabilitation, which all impact on Virchow’s triad.20, 21, 22 In addition, ischaemic stroke is a thrombo-inflammatory condition,²³ characterised by platelet activation, oxidative stress and the presence of increased numbers of proinflammatory neutrophils and neutrophil extracellular traps, which may further promote VTE.24, 25

Haemorrhagic transformation of ischaemic stroke

Haemorrhagic transformation (HT) following acute ischaemic stroke occurs due to disruption of the blood–brain barrier (BBB) and reperfusion injury.26, 27 Acute HT occurs within 18 h of stroke onset, and delayed HT occurs after 18 h.²⁶ Matrix-metalloproteinases (MMP), in particular MMP-9, play a key role in the development of HT. In the acute phase, this is mostly released from activated neutrophils in the peripheral blood, whereas in delayed HT, it is primarily sourced from microglia and astrocytes.28, 29 An increased neutrophil:lymphocyte ratio was shown to be associated with risk of HT in over 1,000 patients with acute ischaemic stroke.³⁰

Fibrinolysis initiated by exogenous tissue plasminogen activator (tPA) causes a consumptive coagulopathy, with prolongation of the prothrombin and partial thromboplastin times, which may last more than 24 h post-infusion.31, 32, 33 This coagulopathy is driven primarily by marked reductions in fibrinogen levels, which correspond with the risk of subsequent HT and parenchymal haematoma formation.³⁴ Alongside causing clot lysis, tPA promotes MMP-9 release from neutrophils and activates an agonist of platelet-derived growth factor receptor alpha, which further promotes disruption of the BBB.35, 36 A meta-analysis of all completed phase 3 randomised controlled trials of alteplase reported HT in 6.8% of alteplase-treated participants, with an OR of 5.55 (95% CI 4.01–7.7) compared with placebo.³⁷ Overall, rates of intracranial haemorrhage (ICH) related to thrombolysis use have been reported at 2–7% in post-marketing evaluation.38, 39

Antiplatelet therapy may potentially further increase the risk of HT. Dual antiplatelet therapy (DAPT) is recommended for patients following a minor stroke or high-risk transient ischaemic attack (TIA) with only a minor impact on the risk of ICH noted in clinical trials, compared with aspirin monotherapy (rates of HT <0.5% for monotherapy or DAPT with aspirin and clopidogrel or ticagrelor). 40, 41, 42

In summary, acute ischaemic stroke carries a risk of HT, which is exacerbated by thrombolysis and potentially also by antiplatelet medications required in the initial management of these patients.

Development of VTE post-ICH

Worryingly, VTE is more prevalent following ICH than ischaemic stroke. Risk of DVT is approximately four times greater, with in-hospital VTE rates of 1–7% reported, the majority of which occur within the first week after presentation.43, 44, 45, 46

Severity of haemorrhage, age, prolonged hospitalisation, functional impairment post-stroke (especially immobility) and comorbidities such as the presence of cancer, pulmonary circulation disease, infection and coagulopathy have been identified as risk factors for VTE post-ICH.47, 48, 49 A number of authors have created risk prediction models for in-hospital DVT, although none have reached clinical practice.50, 51 One group created a nomogram to predict VTE based on only three variables: NIHSS score at presentation, Glasgow coma scale score on admission and D-dimer level. A simple tool to identify high-risk patients is attractive; however, this score was derived from a reasonably modest sample size of 369 patients, with a high rate of VTE (22.5%) observed, and limited information provided regarding implementation of thromboprophylaxis.⁵⁰ Another group produced a risk assessment model based on age, haematoma volume, presence of extension into the subarachnoid space, pneumonia, gastrointestinal bleeding and length of stay, termed the ICH-VTE score. This was derived from a cohort of over 1,300 patients and validated in nearly 1,000 more.⁵¹ However, whether higher-risk patients benefit from a different management strategy is not known.

The size of the haematoma itself is capable of causing secondary brain injury, which would warrant an inflammatory response. The complement cascade is activated as inflammatory markers are raised, increasing the patient’s risk of developing a clot.⁵² Another factor contributing to this inflammation is raised intracranial pressure and midline shift. In response to the bleed, the immune system tries to compensate by releasing inflammatory cytokines (IL-6 and TNF-α),⁵³ which propagate the production and release of fibrinogen and von Willebrand factor from the liver.

VTE prophylaxis after ischaemic stroke

Non‐pharmacological prophylaxis

Intermitted pneumatic compression stockings (IPCs) have been identified as a means of reducing the risk of DVT in hospitalised surgical patients. A meta-analysis that analysed over 16,000 patients from 70 RCTs reported a rate of 7.3% in patients wearing IPCs versus 16.7% in those with no intervention (p < 0.001).⁵⁴ To investigate whether this is applicable to hospitalised stroke patients, another study examined graduated compression stockings (GCS) and IPCs in 2,615 and 177 acute ischaemic stroke patients respectively. Although IPCs did not have a significantly improved outcome, there was a trend in reduction of DVTs versus control groups of providing ‘best medical intervention only’ (OR 0.45, CI 0.37–2.89).⁵⁵ The Clots in Legs Or sTockings after Stroke (CLOTS3) Trials reviewed 2,876 patients across 76 centres in the UK, reporting an absolute risk reduction of DVT by 3.6% associated with use of IPCs.⁵⁶ Out of 1,438 control patients 12.1% had a DVT, whereas in those given IPCs the rate was 8.5% (CI 1.4–5.8). IPCs have also been identified as a valuable method for prophylaxis when pharmacological intervention is contraindicated; however, complications of these devices include skin irritation, puritus and, rarely, tissue damage and infection, which may limit their value.⁵⁷

Another non-pharmacological intervention is the geko™ electronic stimulation device.⁵⁸ This device sits below the knee and stimulates the common peroneal nerve to contract the calf muscle, providing an imitation of walking. By increasing venous return and reducing stasis, the geko™ device is able to improve circulation and theoretically prevent clots from forming. The geko™ was utilised in six stroke patients, with DVT rates compared to 35 controls allocated IPCs. The rate of DVT was lower in the group receiving the novel device (22.9% versus 50%) in this small audit report.⁵⁹ This device may be more tolerable from a patient perspective than IPCs, but larger well-designed clinical studies are required to determine its role in clinical practice.

Pharmacological prophylaxis

The value of pharmacologic VTE prophylaxis in hospital inpatients is essentially universally accepted. However, although there is clearly a high risk of VTE following a stroke, the data supporting the routine use of VTE prophylaxis in these patients are less clear. The International Stroke Trial (IST) randomised 19,435 patients post-ischaemic stroke to up to 14 days of unfractionated heparin (UFH) (5,000 or 12,000 IU twice daily) compared with ‘no heparin’. PEs occurred in 0.5% of the heparin arm and 0.8% of the no heparin arm within 14 days, whereas HT was more common in patients receiving anticoagulation (1.2% vs. 0.4%).⁶⁰ 312 patients were randomised to high-dose nadroparin (4,100 IU twice daily), low-dose nadroparin (4,100 IU once daily) or placebo for 10 days, with the first dose received within 48 h of presentation. HT on routine CT scan at day 10 was present in 6.2%, 8.6% and 12% of patients receiving high-dose LMWH, low-dose LMWH or placebo respectively. No patients receiving LMWH developed a DVT, versus one patient in the placebo arm.⁶¹ The PROTECT (prophylaxis of thrombotic and embolic events in acute ischaemic stroke with the LMWH certoparin) trial randomised 545 patients within 24 h of stroke onset to certoparin (3,000 IU once daily) or UFH (5,000 IU three times daily) for 12–16 days. The primary endpoint of proximal DVT, PE or death due to VTE occurred in 6.6% and 8.8% of the LMWH and UFH arms, respectively, and similarly proximal DVT occurred in 6.6% and 8.4%. The trial concluded that certoparin was non-inferior to UFH.⁶² The PREVAIL (efficacy and safety of enoxaparin versus UFH for the prevention of VTE after acute ischaemic stroke) study randomised 1,762 patients with acute ischaemic stroke within 48 h of symptom onset to 40 mg enoxaparin once daily or 5,000 IU UFH twice daily for 10 days. Significantly more patients in the UFH arm developed VTE (18% vs. 10%, p = 0.0001), which was primarily driven by an increased rate of asymptomatic DVT (17% vs. 10%, p < 0.0001). ICH occurred in 1% in both arms, and bleeding rates overall were similar.⁶³

A number of meta-analyses have been published in this area. Analysis of eight randomised trials (15,405 patients), comparing heparin prophylaxis with no heparin, reported an increase in major bleeding events (OR 1.66, 95% CI 1.20–2.28), but no impact on death or rates of PE.⁶⁴ A more recent Cochrane review of nine RCTs (3,137 patients) comparing LMWH with UFH demonstrated a reduction in DVT risk in the LMWH group (OR 0.55, 95% CI 0.44–0.70) but no difference in risk of DVT, HT or mortality rate.⁶⁵

These data, while useful, have significant limitations. Patients with a history of ICH, uncontrolled hypertension, or severe stroke-related morbidity were excluded from the majority of randomised studies, hence generalisability is compromised. It is also not clear when the appropriate time to start VTE prophylaxis in all patients is, nor how long this should be continued for.

Factor Xa inhibitors have not been trialled specifically in the stroke population, but provide an attractive oral option for longer-term prophylaxis than subcutaneous injections. The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post‐Discharge Venous Thrombo‐Embolism Risk) and MAGELLAN (Multicentre, randomised, parallel‐group efficacy and safety study for the prevention of venous thromboembolism in hospitalised medically ill patients comparing rivaroxaban with enoxaparin) studies reviewed the use of low-dose rivaroxaban (10 mg once daily) for 25–45 days after hospitalisation.66, 67 A composite outcome of symptomatic DVT, non-fatal PE, myocardial infarction and ischaemic stroke occurred in 1.8% of rivaroxaban-treated patients compared with 2.31% of the placebo cohort. Approximately 16% of each arm were in hospital due to an ischaemic stroke; however, no subgroup analysis has been provided.

Guideline recommendations

There are few guidelines specifically addressing the topic of VTE prophylaxis post-acute ischaemic stroke. The European Stroke Organisation (ESO) 2016 guidelines⁶⁸ and the American Society of Haematology 2018 guidelines suggest VTE prophylaxis for patients with stroke, but make no recommendations regarding timing, nor any distinction between patients receiving tPA or not.⁶⁹ Conversely, the National Clinical Guideline for stroke for the UK and Ireland recommends against routine LMWH thromboprophylaxis.⁷⁰ Guidelines are summarised in Table 1,68, 69, 70 and relevant interventional trials in Table 3.

Table 1.

Guidelines regarding pharmacological VTE prophylaxis in patients with ischaemic stroke.

Ischaemic stroke
Guideline	VTE prophylaxis	Recommendations
European Stroke Organisation (ESO) guidelines for prophylaxis for VTE in immobile patients with acute ischaemic stroke, 2016	UFH/LMWH	Consider VTE prophylaxis in immobile patients in whom the benefits of reducing the risk of VTE are high enough to offset the increased risk of ICH and extracranial bleeding associated with their use
American Society of Haematology 2018 guidelines for management of VTE: prophylaxis for hospitalised and non-hospitalised medical patients	LMWH/fondaparinux/UFH if the other options are not available	VTE prophylaxis recommended in acutely unwell medical patients including those with stroke
National Clinical Guideline for Stroke for the UK and Ireland, 2023		VTE prophylaxis should not be routinely given

Table 3.

Summary of key trials and findings in article.

Trial name	Study type and objectives	Key findings
53CLOTS 3 Trial: Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke	Multicentre RCT – Whether IPCs are effective in reducing DVT in immobile patients’ post-acute stroke (n = 2,876)	•Incidence of proximal lower limb DVT was lower in patients managed with an IPC (8.5% vs 12.1%, ARR 3.6%, 95% CI: 1.4–5.8%) •Reduced 30-day mortality in the IPC group (27.2% vs. 34.1%, p < 0.0001)
57The International Stroke Trial (IST)	RCT – Assessing mortality rates of patients given antithrombotic medication (aspirin, subcutaneous heparin, both or neither) post an ischaemic stroke (n = 19,435)	•No difference in mortality between groups given heparin versus no heparin (9.0% vs. 9.3%) •Recurrence of ischaemic stroke was reduced in heparin arms (2.9% vs. 3.8% p = 0.005) •HT was more frequent in patients receiving heparin (1.2% vs. 0.4% p < 0.00001) •Recurrence of ischaemic stroke was reduced in patients receiving aspirin (2.8% vs. 3.9% p < 0.001), without a significant increase in HT
58Low-molecular-weight heparin for the treatment of acute ischaemic stroke	RCT – Comparing high and low doses of LMWH with placebo in treatment of ischaemic stroke to look for better patient outcomes at 6 months (n = 312)	•HT at day 10 occurred in 6.2% (high-dose LMWH), 8.6% (low-dose LMWH) and 12% (placebo) •Patients receiving LMWH had a reduced rate of death/dependency compared with the placebo arm (RR for high-dose LMWH vs. placebo 0.69, 95% CI 0.54–0.9, RR for low-dose LMWH vs. placebo 0.81, 95% CI 0.64–1.02)
59PROTECT Trial	Multicentre RCT – comparing efficacy of LMWH to UFH as VTE prophylaxis in acute stroke patients (n = 545)	•Mortality from VTE occurred at similar rates in patients given LMWH and UFH (6.6% vs. 8.4%, p = 0.008) •The difference in HT in patients receiving LMWH or UFH (1.1% vs. 1.8%, unknown significance2222)
60PREVAIL Study	Open Label Randomised Comparison – Comparing the safety and efficacy of enoxaparin versus UFH, using NIHSS scoring, as VTE prophylaxis for acute stroke patients (n = 1,762)	•Enoxaparin was superior to UFH in preventing VTE development (10% vs 18%, 95% CI: 0.44–0.76, p = 0.0001) •Rate of HT was the same for both regimens (8%) •Enoxaparin appears to have greater benefit as a thromboprophylaxis than UFH
67MARINER Trial	RCT – Investigating the risk of symptomatic VTE in recently discharged patients given rivaroxaban versus placebo for thromboprophylaxis (n = 12,019)	•No significant difference in VTE rate in patients given rivaroxaban versus placebo (0.83% vs. 1.10%, p = 0.14) •The difference in HT rate comparing rivaroxaban and placebo was 0.28% vs. 0.15% respectively
66MAGELLAN Trial	Multicentre RCT – Evaluating the safety and efficacy of rivaroxaban versus enoxaparin versus placebo as thromboprophylaxis in acutely ill inpatients (n = 8,101)	•Significant reduction in VTE at day 35 in patients receiving rivaroxaban compared with placebo (4.4% vs 5.7%, p = 0.02) •Significantly more bleeding seen in the rivaroxaban arm (day 10: 2% vs. 1.2%, p < 0.0001; day 35: 4.1% vs. 1.7%, p < 0.0001)
68Prevention of deep vein thrombosis and pulmonary embolism in patients with acute intracerebral haemorrhage	RCT – Investigating the safety of low-dose LMWH in comparison to compression stockings in preventing a DVT and haematoma enlargement in patients with acute ICH (n = 75)	•No haematoma enlargement was noted in either arm of the study at 72 h, 7 or 21 days post-presentation
69PREVENTIHS Study	RCT– enoxaparin compared with placebo as thromboprophylaxis in ICH patients (n = 73)	•Non-significant reduction in VTE at 10 days in the enoxaparin arm (15.8% vs. 20.0%, RR 0.79, 95% CI: 0.29–2.12) •Non-significant reduction in HT in the enoxaparin arm (2.6% vs. 8.6%, RR 0.32, 95% CI: 0.03–2.82)

VTE prophylaxis after intracerebral haemorrhage

Pharmacological prophylaxis

There is an even greater paucity of large, randomised studies of pharmacologic VTE prophylaxis in patients with ICH compared with ischaemic stroke. One group randomised 75 patients to enoxaparin (40 mg once daily) versus compression stockings from 48 h after presentation. There was no evidence of haematoma enlargement at 72 h,7 days and 3 weeks in either group. Patients had planned doppler ultrasound and CT pulmonary angiography after 1 week. There were three asymptomatic DVTs in the LMWH group and one in the control arm, as well as one asymptomatic PE in either arm. One patient not allocated to LMWH sustained a symptomatic PE on day 17.⁷¹ The PREVENTIHS study (prevention of VTE in haemorrhagic stroke patients) was a phase 3 RCT comparing 40 mg enoxaparin once daily for 10 days versus placebo. Patients were enrolled 72 h after ICH, provided that a CT did not show further bleeding at that timeframe, and underwent Doppler ultrasonography after 10 days. DVT was detected in 16% of the LMWH group and 20% of the control group (RR 0.79, 95% CI 0.29–2.12), which was not statistically significant; however, the study was terminated early with only 73 patients enrolled due to poor recruitment.⁷²

Meta-analyses have also provided equivocal results. Review of four studies of 1,000 patients, in which heparin prophylaxis was commenced between 24 h and 6 days post-ICH, identified a significant reduction in PEs (1.7% vs. 2.9%, RR 0.37; 95% CI 0.17–0.8) in favour of VTE prophylaxis, and a non-significant reduction in mortality but increase in haematoma enlargement.⁷³ A more recent analysis of nine studies including those in the previous meta-analysis (n = 4,055), in which prophylactic heparin was implemented from 24 h to 7 days post-presentation, also showed no significant impact on haematoma extension, mortality or extracranial bleeding.⁷⁴

In terms of the optimal time to commence VTE prophylaxis, one group allocated 126 patients to early (within 48 h) or late (after 48 h) LMWH prophylaxis, with no difference in haematoma expansion reported.⁷⁵ Another recent study compared enoxaparin (20 mg twice daily) given 24 (early) or 72 (late) hours after ICH in 139 patients, excluding those requiring neurosurgery. Patients underwent CT brain and Doppler ultrasound prior to discharge or as clinically indicated. Two patients in the early group and one in the late group developed DVT. Haematoma enlargement occurred in eight patients in each arm.⁷⁶

Guideline recommendations

Several guidelines make weak recommendations to consider VTE prophylaxis after 24–48 h in the absence of continued bleeding. These are summarised in Table 2;77, 78, 79, 80, 81 however, real-world practice differs significantly. Of 32,690 patients with ICH who survived to day 2 of hospitalisation, only 16.5% received any anticoagulation,⁸² and in a survey of UK stroke clinicians, 28% felt that anticoagulation should not be used at all, which rose to 38% for patients after a lobar bleed, likely due to concerns regarding re-bleeding from possible CAA.⁸³

Table 2.

Guidelines regarding pharmacological VTE prophylaxis in patients with haemorrhagic stroke.

Intracranial haemorrhage
Guideline	VTE prophylaxis	Recommendations
American Heart Association/American Stroke Association 2022 Guideline for the management of patients with spontaneous ICH	UFH/LMWH	Consider in non-ambulatory patients 24–48 h post-ICH
Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Haemorrhage, 7th Edition Update 2020	LMWH	May be given 48 h post-ICH provided documented evidence of haematoma stabilisation on neuroimaging
Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Evidence-Based Guideline: A Statement for Healthcare Professionals from the Neurocritical Care Society 2016	UFH/LMWH	Consider 48 h post-ICH in patients with stable haematomas
European Stroke Organization (ESO) 2014 Guidelines for the management of spontaneous intracerebral haemorrhage		Insufficient evidence available to make a recommendation
The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee 2006Recommendations for the management of intracranial haemorrhage - part I: spontaneous intracerebral haemorrhage	UFH/LMWH	Consider after 24 h, especially in patients at high VTE risk

A summary of available guideline recommendations is provided in Table 2. Where available, these essentially suggest commencing VTE prophylaxis 24–48 h post-ICH if feasible. Of note, no single guideline discusses both ischaemic and haemorrhagic stroke management. Relevant interventional trials are summarised in Table 3.60, 61, 62, 63, 66, 67, 71, 72, 84

Conclusion

Mortality due to stroke and its complications has become a growing concern in the developed world. Of the multiple complications a patient can develop, VTE is one of the more common ones, with a mortality rate of up to 30%.⁸⁵ The development of VTE appears to rely heavily on venous stasis, endothelial dysfunction and a thromboinflammatory state in both ischaemic and haemorrhagic stroke, with the highest risk of VTE occurring within the first 2 weeks. Evidence underpinning the importance of VTE prophylaxis post-stroke is impaired by small sample sizes and exclusion of patients at increased risk of both bleeding and thrombosis. Thrombolysis increases the risk of HT but wasn’t standard practice at the time of some of the VTE prophylaxis trials cited, and patients with ICH requiring neurosurgical intervention were generally excluded. These limitations in both the reported trials and guidelines are highlighted by variable real-world practices and poor use of pharmacological prophylaxis. Preclinical data suggest that targeting neutrophil activation, adhesion to the endothelium and interaction with platelets may reduce VTE risk; however, these approaches have yet to reach clinical trials. Future studies with appropriate inclusion criteria are still desperately needed to determine the best way to utilise VTE prophylaxis in these patients.

Future research

What is the optimal agent for VTE thromboprophylaxis after acute stroke – LMWH versus DOAC?

What is the optimal dose for VTE thromboprophylaxis?

When should VTE thromboprophylaxis be commenced after IS and ICH?

What is the role for non‐pharmacological agents and in which patients specifically?

Can anti-inflammatory strategies reduce VTE risk in patients?

CRediT authorship contribution statement

Jecko Thachil: Writing – review & editing, Visualization, Supervision. Dawn Swan: Writing – review & editing, Visualization, Resources, Data curation. Shiksha Guru: Writing – original draft, Resources, Investigation, Data curation, Conceptualization. Adrian Parry-Jones: Supervision.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.