A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis

Abstract

The outcome of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only favorable in ≈ 40% of acute ischemic stroke (AIS) patients. Moreover, in ≈ 6–8% of cases, intracerebral hemorrhage (ICH) develops. We tested whether a modification of clot lysis assay (CLA), might predict therapy outcomes and safety. In this prospective observational study, blood samples of 231 AIS patients, all receiving intravenous rt-PA, were taken before thrombolysis. Cell-free DNA (cfDNA), CLA and CLA supplemented with cfDNA and histones (mCLA) were determined from the blood samples. Stroke severity was determined by NIHSS on admission. ICH was classified according to ECASSII. Short- and long-term outcomes were defined at 7 and 90 days post-event according to ΔNIHSS and by the modified Rankin Scale, respectively. Stroke severity demonstrated a step-wise positive association with cfDNA levels, while a negative association was found with the time to reach 50% lysis (50%CLT) parameter of CLA and mCLA. ROC analysis showed improved diagnostic performance of the mCLA. Logistic regression analysis proved that 50%CLT is a predictor of short-term therapy failure, while the AUC parameter predicts ICH occurrence. A modified CLA, supplemented with cfDNA and histones, might be a promising tool to predict short-term AIS outcomes and post-lysis ICH.

Intravenous Thrombolysis Combined with Arterial Thrombolysis (Bridging Therapy) Effectively Improves Vascular Recanalization Rate in Patients with Cerebral Infarction

“…Intravenous thrombolysis is currently the main method to open blood vessels in the early stage of cerebral infarction, which can promote local blood circulation through drug dissolution, thus alleviating the ischemia and hypoxia state of brain tissue at the lesion site. Meanwhile, it can speed up the fibrinolysis process and reduce the number of stents used for thrombectomy and the frequency of microvascular thrombus regeneration [ 17 ]. However, intravenous thrombolysis alone can easily lead to a low vascular patency rate and a high risk of vascular reocclusion after thrombolysis, which may eventually result in bleeding [ 9 ].…”

A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers

“…In acute ischemic stroke cases, the advanced treatment is recombinant tissue plasminogen activator (rt-PA), by intravenously drug delivery to dissolve the blood clot (<4.5 hr) after the onset of the symptoms [2,4]. Despite the fact that around a quarter of ischemic stroke patients arrive at the hospital within the therapeutic time window, only 40% of these patients receive thrombolytic therapy with rt-PA [5,6]. This is due to the inability to accurately predict who will beneficiate from the treatment without suffering severe side effects, like hemorrhagic transformation (HT), which causes significant morbidity and mortality in stroke patients.…”

“…A set of protein biomarkers present in blood at certain concentrations have revealed the potential to predict the right candidates for rt-PA treatment [2,7]. Cellular fibronectin (c-Fn) and matrix metallopeptidase 9 (MMP9) are biomarkers associated with the acute cases and relevant for patient stratification [5][6][7][8][9]. Besides recently, we performed a clinical study using a magnetoresistive (MR) biochip platform that has proven to detect within the clinical and relevant dynamic range those biomarkers [10]; the sample preparation is still a crucial step and very time-consuming.…”

Predicting 1-Hour Thrombolysis Effect of r-tPA in Patients With Acute Ischemic Stroke Using Machine Learning Algorithm

“…Nevertheless, not all patients can benefit from this therapeutic regimen. Only approximately 40% of the treated patients show improvement, whereas other patients still experience a low recanalization rate ( Orban-Kalmandi et al, 2021 ). Thus, predicting the intravenous thrombolytic effect at an early stage is important for both the clinician and patient.…”