Abstract

Rationale: More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success.Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early.Methods: This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders.Outcomes: The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study.Discussion: If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.

Highlights

  • Despite the increasing use of mechanical thrombectomy (MT), thrombolysis with recombinant tissue-type plasminogen activator remains a cornerstone of acute ischaemic stroke treatment

  • Samples from patients who received thrombolysis and underwent transcranial doppler (TCD) before thrombolysis, and at least once within 6 h after thrombolysis will be included in the primary analysis

  • Samples from patients who received thrombolysis and underwent angiography, either computed tomography (CT) or magnetic resonance imaging (MRI), before and 24-h post-thrombolysis will be included in secondary analyses

Read more

Summary

Introduction

Despite the increasing use of mechanical thrombectomy (MT), thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) remains a cornerstone of acute ischaemic stroke treatment. While great strides have been made with regard to selecting patients who are likely to have a favorable clinical outcome after thrombolysis [4,5,6], the reasons some patients fail to recanalize remain largely unknown. Previous studies have examined baseline levels of individual fibrinolysis markers in acute ischemic stroke patients [7] but this approach is limited as the potency of thrombolysis depends on the net capacity of a patient’s plasma to generate plasmin from plasminogen in response to rt-PA and this may not necessarily correlate with baseline levels of individual fibrinolysis markers. We aim to examine association between net plasmin generation in the presence of rt-PA and clinical outcomes, time to recanalization

Objectives
Methods
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call