Mechanical thrombectomy for acute stroke in pregnancy

Abstract

Several recent randomised control trials have shown adjunctive endovascular mechanical thrombectomy to be an effective and safe treatment for acute stroke superior to medical therapy alone. Despite this, questions remain over certain groups of patients that have been excluded from these studies, such as pregnant women. We believe this is a topic of increasing clinical significance with minimal data in the literature. In this article we discuss stroke in pregnancy and highlight the important technical considerations of endovascular mechanical thrombectomy, including minimising radiation exposure to the mother and fetus.

Introduction

Large vessel acute ischaemic stroke in pregnancy is one of the leading causes of neurological disability, morbidity and mortality in developed countries.¹ The risk of suffering stroke in pregnancy is approximately three times higher than the general young adult population, affecting 30 per 100,000 pregnancies.² Despite recent advances in stroke treatment, reported mortality rate in this cohort of pregnant patients remains relatively high at 10–13%.^3,4 The case fatality rate is reported to be approximately 20%; whilst 45% of those who survive are discharged with significant disabilities. A further 30% will require transfer to rehabilitation facilities.⁵ Therefore, early identification of stroke in pregnancy is crucial in order to initiate urgent and effective management.

Stroke in pregnancy

Pregnancy is a hypercoagulable state confounded principally by two major processes: an increased production of endogenous clotting factors and a significantly reduced proportion of naturally occurring anticoagulants. The combination of these two factors leads to reduced fibrinolytic ability, thus increasing the risk of thrombotic events, including thromboembolic stroke.⁶ Regarding the time course of pregnancy, the risk of stroke appears to be highest in the postpartum period. Furthermore the risk of stroke in pregnancy is known to increase with higher age and in certain ethnicities, particularly those over the age of 35 years and of African American descent.⁵

While ischaemic stroke is more common than haemorrhagic stroke in pregnancy, the latter also occurs with higher incidence than in an age-matched non-pregnant population (40% versus 22%).⁵

Investigations for stroke must be carried out promptly in pregnant women presenting with new neurological deficit, whilst taking fetal risk into consideration. In cases where angiography or venography is required, adequate hydration status of the mother and fetal radiation dose are two of the major factors that should be considered.⁷

Current stroke management in pregnancy

Current international recommendations are to treat acute ischaemic stroke in an acute stroke unit where specialist services are available.⁸ There is currently no consensus on the use of thrombolytics in acute ischaemic stroke in pregnancy. However, outside pregnancy, this is the recommended treatment of choice, alongside mechanical thrombectomy.^9,10 The most commonly used thrombolytic agent is alteplase, a fibrin-specific tissue plasminogen activator (tPA). However, the effectiveness and safety profile of thrombolytic agents in the treatment of acute ischaemic stroke in pregnancy is not well known, as pregnant women have historically been systematically excluded from randomised controlled trials investigating acute stroke reperfusion therapies.¹¹

Therefore a concern for potential adverse effects on the mother and fetus often serve as a basis for reluctant use of thrombolysis. For the mother these complications include intracranial and extracranial haemorrhage, intra-abdominal/intramuscular haematoma and death (6.1–6.3% case fatality rate), whilst fetal complications include miscarriage, placental abruption and stillbirth.¹²

Support for thrombectomy in a younger childbearing population

Outside pregnancy, endovascular mechanical thrombectomy is emerging as a promising therapeutic option for large vessel acute ischaemic stroke.^8,13–25

Older patients, however, have shown to have a suboptimal benefit from mechanical thrombectomy, often due to reduced recanalisation success secondary to tortuous atherosclerotic vasculature.^26,27

When looking at patients of a younger population, Mocco et al. first brought together a study comprising seven patients under 35 years of age who all underwent endovascular stroke intervention.²⁸ Five out of seven regained independent function at time of discharge, whilst the remaining two were found to have regained functional independence by the time of follow-up at 25 months.

Chalouhi et al. and Zanaty et al. demonstrated successful recanalisation in 93% in a cohort of 45 patients aged 55 or younger, with a satisfactory 90-day outcome (modified Rankin scale (MRS) scale 0–3) achieved in 90%.^29,30 Favourable outcomes (MRS scale of 0–2) were 77.5% for all patients; however, in those aged 35 or less, favourable outcomes increased to 89%, highlighting the increased benefits of endovascular intervention in the younger population.

On a larger scale, the HERMES study, a meta-analysis of five randomised controlled trials, showed that in a total study population of 1287 patients, good functional outcomes at 90 days were 46% with mechanical thrombectomy versus 26.5% with best medical therapy alone.²⁵

When specifically looking at the 18–49 year patient subgroup, that is the cohort paralleling that of the pregnant population, thrombectomy was shown to be significantly effective when assessing MRS at 90 days, displaying the lowest MRS of any patient cohort at 90 days post-thrombectomy. Whilst in this analysis we did not know each patient’s individual initial National Institutes of Health Stroke Score, there is significant support that those in younger cohorts have better functional recovery than their older, treatment-matched counterparts (see Figure 1).^31–33

Figure 1.

Modified Rankin scale (MRS) scores at 90 days.²⁵ Demonstrates the distribution of scores at 90 days in the intervention and control groups in both the overall trial population, and for patients treated with or without intravenous alteplase. Significantly lower MRS scores were seen in the interventional groups irrespective of whether intravenous thrombolysis was given.

The results of this HERMES analysis went on to calculate that for mechanical thrombectomy, the number needed to treat (NNT) was 2.6. This is a remarkable number given that, by comparison, cardiac angioplasty has an NNT of approximately 14–26,³⁴ truly highlighting the significance that thrombectomy holds for future stroke therapy.

In general, endovascular interventions are further optimised in younger patients by the principle that they will typically have less atherosclerotic and tortuous vessels as compared with an older counterpart, thereby facilitating a higher theoretical likelihood of successful recanalisation. Therefore, when combining the supporting data of successful recanalisation, low post-stroke morbidity and the significant recovery of independent function, endovascular stroke treatment should be a highly recommended treatment option for younger patients.

The recommended practice for management of acute stroke was initially updated to advise thrombectomy for patients presenting within 4.5 h with a proximal vessel occlusion, aiming to undergo the procedure before the 6-h mark.³⁵ However, it is now recommended that thrombectomy should be performed beyond the 6-h timeframe, moving to a timeframe closer to that of 16 h, with some cases suitable up to 24 h after onset of symptoms.⁸

This move has come in large part from the emergence of the DEFUSE 3 and DAWN trials, which demonstrated that in select patients undergoing stroke treatment beyond 6 h of symptom onset, thrombectomy combined with medical therapy was five times more likely than medical therapy alone to result in 90-day functional independence, with no significant difference in 90-day mortality.^36–38

Whilst complication can include bleeding and vessel perforation, there has been no established increased risk of haemorrhage or serious adverse events when performing mechanical thrombectomy in combination with intravenous tPA, whilst stent retrieval devices are also deemed to be safe.³⁹

Regarding cost effectiveness, a study was performed in 2015 using five randomised controlled trials, which calculated that thrombectomy gained a £7061 cost per quality-adjusted life year (QALY) over 20 years.⁴⁰ This value is well below the current £30,000 per QALY threshold that the National Institute for Health and Care Excellence use to qualify cost–efficacy of new treatment options.

The National Health Service has also issued a formal statement of intent to provide a substantial increase in the provision of thrombectomy services in the coming years (see Figure 2).⁴¹

Figure 2.

National Health Service (NHS) agenda for stroke management.⁴¹ Highlighting the vision of the NHS to increase the number of thrombectomy providers to ultimately deliver one of the best rates in Europe by 2025.

Application of thrombectomy in pregnancy

Despite substantial evidence, questions remain over certain groups of patients excluded from thrombectomy trials, including pregnant women. Experience with this procedure in pregnancy has been limited due to concerns over radiation exposure and risk of arterial dissection, particularly in late pregnancy.⁴² As a result no clear guidelines currently exist for the management of acute stroke in pregnant patients. To date, few cases of pregnant patients undergoing mechanical thrombectomy have been reported. Aaron et al. in 2016 first reported a two case series using aspiration thrombectomy for two women in the third trimester who recovered successfully with good fetal outcomes.⁴³ Bhogal et al. in 2017 reported two cases treated successfully with mechanical thrombectomy in the third trimester with similarly positive outcomes for both mother and fetus.⁴⁴

Three further cases were reported in 2019, all with positive outcomes.^45–47 One of these cases by Blythe et al. reported of a pregnant patient who had developed thrombocytopaenia during pregnancy followed by a right middle cerebral artery stroke. Successful thrombectomy resulted in complete vessel recanalisation and delivery of a healthy newborn 5 days later. This case was of particular significance as; due to the co-existing thrombocytopaenia on this occasion, unlike other cases, no adjunctive thrombolytic therapy was given due to the posed risk of bleeding.

In clinical practice there has been reluctance to perform this procedure in pregnancy due to the perceived risks of radiation exposure to both mother and fetus, arterial dissection, and possible association with adverse physiological changes to the cardiovascular system. Any potential risk of exposing the fetus to the effects of ionising radiation can be minimised using several methods that are also used in many paediatric interventional radiology procedures. These include the use of lead shielding, pulsed as opposed to continuous fluoroscopy, narrow collimation, selective magnification and reducing radiation scatter by minimising the air gap between the flat panel detector and patient.⁴⁸ Adjustments of fluoroscopic parameters, however, come with a caveat with the need to provide satisfactory image quality with which to work.⁴⁸

Regarding dose, the typical dose threshold for fetal radiation is in the range of 50–100 mGy. A computed tomography head dose to the uterus is measured at 0 mGy as the true value is so small.^49,50

A recent study of three cases of mechanical thrombectomy performed in pregnancy resulted in a mean estimated effective fetal dose of 0.024 (±0.018) µGy.⁵¹ A general consensus has emerged that when the fetal radiation dose is less than 50 mGy the non-carcinogenic risk, which includes abortion or fetal malformation, is negligible compared with the other risks encountered in pregnancy.⁵¹

In conclusion, ischaemic stroke in pregnancy is associated with significant morbidity and mortality to the mother and fetus. Mechanical thrombectomy has shown to be a treatment that has remarkable outcomes, which improve furthermore in the younger cohort, correlating with the age bracket of females in pregnancy.

With collaborative multidisciplinary management and liaison with specialist stroke services, mechanical thrombectomy has the potential to emerge as an attractive, cost-effective and safe alternative for women with acute ischaemic stroke in pregnancy.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

Not applicable.

ORCID iD

Saminderjit Kularhttps://orcid.org/0000-0003-3437-0918