SWATH-MS for prospective identification of protein blood biomarkers of rtPA-associated intracranial hemorrhage in acute ischemic stroke: a pilot study

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.