Relation of Serum Alpha 2-Antiplasmin to Clinical Response to Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Strokes without Large Vessel Occlusion

Abstract

Abstract Background Stroke is ranked as the second leading cause of death worldwide with an annual mortality rate of about 5.5 million. Not only does the burden of stroke lie in the high mortality but also the high morbidity. Recent studies revealed that up to 50% of survivors being chronically disabled in 2022. Thrombolysis has limited efficacy in the presence of large volume clots, thrombus ultrastructure, hemorrhagic transformation, high National Institutes Of Health Stroke Scale (NIHSS) prior to rtPA and thrombolysis resistance due to the presence of plasminogen activator inhibitor-1(PAI-1) and alpha 2-antiplasmin. Plasminogen is converted to plasmin by plasminogen activator and plasminogen activator can be inhibited by plasminogen activator inhibitors 1 and 2. On the other hand, plasmin itself is directly inhibited by alpha 2- antiplasmin, an ultrafast covalent inhibitor, which accounts for about 90% of plasmin inhibition in vivo and antagonizes the action of rtPA which consequently prolong clot lysis. Aim of the Work To identify the relationship between serum alpha 2-antiplasmin, various risk factors and clinical response to recombinant tissue plasminogen activator in ischemic cerebrovascular stroke. Patients and Methods This is prospective cohort study was conducted at Ain Shams University Hospitals on acute ischemic stroke patients who received thrombolysis, met the inclusion and exclusion criteria. A blood sample to measure serum alpha 2-antiplasmin was obtained before receiving thrombolysis and patients were followed up for 3 months. Results A study on 35 patients showed that there is significant correlation between atrial fibrillation and poor functional outcome in stroke patients who received thrombolysis with p- value=0.033. Also, it shows there is significant correlation between hypertriglyceridemia and poor outcome with p-value= 0.043. It also shows there is a significant correlation between serum alpha 2-antiplasmin level and resistance to thrombolysis with subsequent poor functional outcome with a cut-off point 493 ng /L with a sensitivity 100% and a specificity 81.8% (p-value=0.001). Conclusion This study shows that alpha 2-antiplasmin levels are correlated with cerebrovascular stroke outcome, high levels are associated with poor functional outcome and resistance to IV thrombolysis. Therefore, its inhibition may be crucial to improve the clinical outcome of stroke in the future.