Abstract
Intravenous recombinant tissue plasminogen activator (rtPA) is, besides mechanical thrombectomy, the highest class evidence based reperfusion treatment of acute ischemic stroke (AIS). The biggest concern of the therapy is symptomatic intracranial hemorrhage (sICH), which occurs in 3–7% of all treated patients, and is associated with worse functional outcome. Finding a method of the powerful identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research. To address this problem, we designed a complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of rtPA-associated ICH. In this paper we present results of blood proteomic and peptide analysis of pilot 41 AIS patients before rtPA administration (the test ICH group, n = 9 or the controls, without ICH, n = 32). We demonstrated that pre-treatment blood profiles of 15 proteins differ depending on whether the patients develop rtPA-associated ICH or not. SWATH-MS quantification of serum or plasma proteins might allow for robust selection of blood biomarkers to increase the prospective assessment of rtPA-associated ICH over that based solely on clinical and neuroimaging characteristics.
Highlights
Intravenous recombinant tissue plasminogen activator is, besides mechanical thrombectomy, the highest class evidence based reperfusion treatment of acute ischemic stroke (AIS)
The former is defined as intracerebral hemorrhage classified as local or remote Parenchymal hematoma type 2 (PH2) within 24–36 h after recombinant tissue plasminogen activator (rtPA) bolus administration with the clinically important deterioration of neurological status, whereas the latter is defined as any hemorrhage with clinical deterioration of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) score
The main enriched Reactome pathways consisted of: integrin signaling, platelet aggregation (FGB, FGG), and response to elevated platelet cytosolic C a2+ (FGB, FGG, ITIH3). In this pilot study we demonstrate that pre-treatment blood proteomic profiles of ischemic stroke patients differ depending on whether the patients develop rtPA-associated intracranial hemorrhage (ICH) or not
Summary
Intravenous recombinant tissue plasminogen activator (rtPA) is, besides mechanical thrombectomy, the highest class evidence based reperfusion treatment of acute ischemic stroke (AIS). Finding a method of the powerful identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research To address this problem, we designed a complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of rtPA-associated ICH. Any homogenous hyperdensity located beyond the borders of the infarct zone quantify the neurological deterioration due to rtPA-related sICH include SITS-MOST (The Safe Implementation of Thrombolysis in Stroke-Monitoring Study) and ECASS III3 The former is defined as intracerebral hemorrhage classified as local or remote PH2 within 24–36 h after rtPA bolus administration with the clinically important deterioration of neurological status, whereas the latter is defined as any hemorrhage with clinical deterioration of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) score
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