QB-2022-001544 - [2025] EWHC 2597 (KB)

I now turn to what would have happened if thrombolysis had been given to Mr Hakmi. I am struck that the clinical position, agreed by Dr Baldwin and Dr Hassan, is that there is an absence of evidence in the literature as to the extent to which thrombolysis is effective with a lacunar stroke, however, it remains recommended.

The agreed starting point is that thrombolysis should not be given if the NIHSS score is less than 4. The process is that thrombolysis unblocks the thrombus, thinning the blood. It is agreed that there is a significant risk of bleeding with thrombolysis which should not be given lightly.

Dr Baldwin considers that the cause of Mr Hakmi’s lacunar stroke was a clot. Dr Hassan’s view is that there is no evidence that thrombolysis would have altered the natural history of Mr Hakmi’s stroke because the stroke was not due to clot but due to atheromatous plaque disease in the middle cerebral artery stem, the evidence is lacking that thrombolysis is effective in this type of stroke.

Dr Baldwin, in his report, states that all people with suspected stroke should be admitted directly to a specialist acute stroke unit. Thrombolysis with Actilyse should be offered within the product licence. In 2016 the maximum time between symptom onset and treatment was 4.5 hours. If thrombolysis is not given then Aspirin 300 mg should be given within 24 hours and after 24 hours if the patient received thrombolysis. For those treated within 3 hours the benefit was even greater. Dr Baldwin referred to an alternative approach to assessing the outcome of intravenous thrombolysis which was used by Whiteley. They assessed the outcome based on the presenting NIHSS score. Figure 3 taken from their paper outlines the modified Rankin score for the different NIHSS. It can be seen that the benefit of thrombolysis is much better for subjects with a lower NIHSS.

The extent of Mr Hakmi’s disability is not agreed. Dr Baldwin considers that on the Modified Rankin Scale (mRS) the score is 3. He scored him at 3 in 2022 and again in 2024. Dr Hassan and Dr Santullo consider it is 2. Dr Baldwin did, however, accept in cross-examination that there is a range of assessment that could be 2 or 3. He believes that Mr Hakmi’s mRS was recorded at 2 on 23 December 2016 because of the treatment he was receiving at the Danesbury Rehabilitation Centre. He attributed the score to the extent of the rehabilitation he received. Dr Hassan considers that the disability has to be quite marked to take it up to category 3. In his view, assistance must be essential and required to manage life.

Dr Baldwin was shown a structured tick-box questionnaire produced by Dr Santullo. His view is that it is reductive and not capable of building in the nuances of disability that is found as a result of his methodology of video training based upon a series of cases. The questionnaire, he believes, cannot include all the activities that are required to be considered in a qualitative approach. He also considers that the questionnaire is of limited use because it has been validated by a small number of people. It has not been directly compared to the conventional approach to the Modified Rankin Scale.

It is common ground that the Emberson paper was trying to establish the benefit of giving thrombolysis, depending on the number of hours that had elapsed after the onset of symptoms. In his report Dr Baldwin considered that the window is 3 ½ hours from the onset of the stroke and that if thrombolysis is given within this time there would probably be a good outcome. In his report and Part 35 answers, he agrees that after 3 ½ hours the outcome would probably be the same because the effect of thrombolysis reduces over time. In his report Dr Baldwin relied on the papers by Emberson and Whitely, to show that on the balance of probabilities, the thrombolysis would have prevented the disability associated with the second stroke. His reliance, however, on the Emberson paper fell away in cross-examination by Mr de Bono. He accepted the difference in principle between an odds ratio, which is a way to compare the relative odds of an event happening in two groups, and the probability of an event occurring. Indeed, the Emberson paper refers itself to thrombolysis “increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit.”

In the Emberson paper the proportion of patients treated with thrombolysis was greater than those who had not been treated with it. The example put by Mr de Bono in cross-examination of Dr Baldwin was that if out of 100 patients, 33 had a better outcome with thrombolysis within 3 hours than 23 who had not been treated with it, then it could not be said that, on the balance of probabilities, Mr Hakmi would have had a better outcome. Dr Baldwin accepted that he could not say, based on the Emberson paper, that Mr Hakmi would probably have had a good outcome had he been treated with thrombolysis. The most that he could say is that he lost the chance of a better outcome. He also agreed that the paper did not distinguish between different types of stroke. Lacunar strokes affect small vessels deep in the brain. He accepted that the Whiteley paper did not take the case further as it was concerned primarily with the risk of intracerebral haemorrhage.

Dr Baldwin relied upon the DRAGON score, developed in Finland. The DRAGON score was developed to try and predict what a patient’s outcome would be if they had thrombolysis by comparing people who had a good outcome with those who had a miserable outcome, respectively 0-2 and 5-6 on the Modified Rankin Score.

He believes that the Mr Hakmi’s DRAGON score would have been 2 which predicts a 96% likelihood of good outcome (mRS 0-2) and a 2% likelihood of a miserable outcome (mRS 5- 6). In his opinion, based on the DRAGON score Mr Hakmi would have survived with a Modified Rankin Score in the range of 0 to 2 with the result that at worst he would have a slight disability.

Dr Hassan considers that the DRAGON score shows no more than that Mr Hakmi would have ended up in same position whether he had had thrombolysis or the not, if he has a score of 0-2. It does not compare what happens if a patient was given thrombolysis or not given thrombolysis. It helps to predict the outcome for individual patients. If Mr Hakmi had been given thrombolysis, he would have ended up with a Modified Rankin Scale of somewhere between 0 and 2, which is the assessment when he left Danesbury. He relied on a paper by Wardlaw which concluded that it was uncertain whether current treatment or prevention approaches are best suited for treatment in lacunar ischaemic stroke. His view is that there is no good evidence to show whether it helps patients with lacunar stroke to give them thrombolysis but the cautious recommendation is that treatment should continue. He also referred to the European Stroke Organisation in 2024, which said that the data on alteplase in lacunar ischaemic stroke is very limited.

Dr Hassan does not consider that the DRAGON score is used in a clinical context. His view was that the main factors in the DRAGON score would equally apply to patients who had not received thrombolysis and probably predict the same outcomes.

They disagree as to whether Mr Hakmi’s NIHSS score was less than 4 and whether he should have been offered thrombolysis. Dr Baldwin considers that if Mr Hakmi was presenting with right hemiparesis, right hemisensory loss, right facial weakness and slurred speech, them his score was likely to be 4.

Dr Baldwin accepts that the policy in place at the Lister Hospital, that a stroke within the previous three months was an absolute contra-indication because the risk of symptomatic haemorrhagic transformation is too high, was within the range of reasonable practice in 2016. At Dr Metcalf’s Trust the policy was that it was a relative contraindication for the use of thrombolysis. The experts are agreed that a stroke 3 months before is a relative not an absolute contradiction for treatment with thrombolysis.