The role of alpha-1 antitrypsin in the prognosis of ischaemic stroke

Abstract

BACKGROUND: Ischaemic stroke is the second cause of death and the first cause of disability in Europe. Nowadays, the only available pharmacological treatment for acute ischaemic stroke is recombinant tissue plasminogen activator (rt-PA). However, it only achieves the reperfusion of the occluded vessel in 50% of the patients. Moreover, only 5-10% of the patients can receive this treatment due to its numerous contraindications. One of the possible complications of the treatment with rt-PA is the haemorrhagic transformation of the stroke. Although it only occurs in 2-7% of the patients, it worsens the recovery and prognosis of the patient. Another fact that might negatively influence in the outcome of the patient is alpha-1 antitrypsin (AAT) deficiency. AAT is the main antiprotease in bloodstream and its activity is crucial to maintain the balance between proteases and antiproteases in order to limit the proteolytic effect of proteases in tissues, for instance in blood-brain barrier (BBB). Thus, AAT deficiency might be related to BBB disruption, neuronal cell death and an increase and exacerbation of the inflammatory response after an ischaemic stroke, worsening the outcome of the patient. OBJECTIVE: To analyse AAT levels in blood samples of patients with acute ischaemic stroke treated with rt-PA, at admission, 2, 6, 24 and 72 hours, and correlate these levels with the functional outcome of the patient at 3 months (modified RANKIN scale). DESIGN AND PARTICIPANTS: The study will consist in a prospective cohort study including consecutive patients suffering from acute ischaemic stroke (independently of the aetiology of the stroke) treated with rt-PA in the Neurology Department of Hospital Dr. Josep Trueta, between 1 June 2020 and 31 November 2022.

METHODS: 5 blood samples will be extracted in the acute phase of stroke (at admission, 2, 6, 24 and 72 hours). Patients will be divided into two groups according to AAT levels at admission: normal levels of AAT (31-2 g/L) versus low levels of AAT (<1 g/L). 196 patients will be required in each group. 3 months after the stroke, the prognosis of the patient will be evaluated using the modified RANKIN scale. AAT levels in the acute phase of the stroke will be compared with levels at 3 months. Infarct volume and the presence of haemorrhagic transformation will be assessed with computed tomography (CT) scan at 24 hours of the stroke, and these variables will be correlated with AAT levels in the acute phase