COVID-19- associated hemostasis alterations and outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

ABSTRACT

Background: Coronavirus disease-2019 (COVID-19) increases the risk of acute ischemic stroke (AIS). Hemostasis alterations and outcomes of reperfusion therapy (thrombolysis or thrombectomy) in COVID-19- positive AIS patients are not well studied, as yet. (Figure Presented) Aims: We aimed to test hemostasis alterations in COVID-19- positive AIS patients receiving intravenous (i.v.) thrombolysis as compared to non-infected AIS patients and to correlate results with therapy outcomes and safety. Method(s) In this prospective observational study, 110 AIS patients receiving i.v. thrombolysis (recombinant tissue plasminogen activator) with/without thrombectomy were enrolled (April 2020-December 2021). Blood samples were taken on admission (within 4.5h of symptom onset), at 1h and 24h post-event. SARS-CoV- 2 RT-PCR test performed on admission confirmed acute infection in 9 cases (COVID-19+ group). Anti-SARS- CoV- 2 antibody test proved convalescence and/or vaccination in 48 patients (post-COVID/ post-vaccination group). Markers of inflammation (CRP, ferritin, IL-6), D-dimer, fibrinogen, von Willebrand factor (VWF) antigen, factor VIII (FVIII) and factor XIII (FXIII) activity, clot-lysis assay, thrombin generation, ROTEM and angiotensin convertase enzyme (ACE)1, ACE2 activities were analyzed. Stroke severity was determined by NIHSS. Therapy-associated intracerebral hemorrhage was classified according to ECASSII criteria. Short-and long-term outcomes were defined at 7 days and 3 months post-event according to the change in NIHSS and the modified Rankin Scale, respectively. Result(s) Stroke severity was significantly greater in the COVID-19+ group. VWF antigen levels were markedly elevated in the COVID-19+ group as compared to non-infected and post-COVID/ post-vaccination groups (323 +/- 72% vs. 248 +/- 75% and 222 +/- 80%, respectively, p = 0.006). FVIII levels were parallel to VWF levels and showed significant elevation in the COVID-19+ group. Short-term outcomes of therapy and the occurrence of hemorrhagic transformation did not differ between groups. Conclusion(s) Elevated FVIII and VWF levels in COVID-19- associated AIS seem to be linked to endothelial cell injury and are associated with more severe stroke. Efficacy of thrombolysis in COVID-19+ AIS patients was similar to non-infected patients in this cohort.