ABSTRACT NUMBER: ESOC2026A1342 DOES DORNASE ALPHA POTENTIATE CLOT LYSIS WITH TENECTEPLASE? INSIGHTS FROM EX-VIVO LYSIS OF THROMBECTOMY CLOTS

Abstract Background and aims Dornase-alpha, a recombinant human deoxyribonuclease-I, can potentiate alteplase-mediated clot lysis via breakdown of neutrophil extracellular traps in stroke clots. We aimed to determine if dornase potentiates clot lysis in combination with tenecteplase ex-vivo in thrombectomy clots retrieved from stroke patients. Methods Forty-two thrombectomy clots were divided and suspended in buffer, pooled citrated or heparinised plasma and incubated with 15nM tenecteplase or in combination with either 10U/ml or 100U/ml of dornase. Clot weight was measured over 120-minutes, and treated clots underwent immunofluorescence. Statistical significance was assessed using linear mixed-effects modelling. Results Addition of tenecteplase to retrieved clots in buffer resulted in a median percentage reduction to 40.7% (IQR:17.0-53.7%) of the initial clot weight after 120-minutes. The addition of 100U/ml of dornase led to significant clot weight reduction to 17.5% (IQR:8.8-27.2%) while the addition of 10U/ml of dornase led to a non-significant reduction to 28.0% (IQR:7.4-45.7%) compared to tenecteplase alone. Further, incubation in citrated and heparinised plasma resulted in a clot weight reduction to 55.7% (IQR:21.6-70.7) and 58.5% (IQR:45.3-73.2) in the presence of tenecteplase respectively, with a non-statistically significant reduction with addition of Dornase. However, there was a significant attenuation in clot weight reduction in plasma compared to buffer in clots treated with tenecteplase and Dornase. Conclusions 100U/ml dornase potentiated ex-vivo tenecteplase mediated clot lysis in buffer but was less effective at lower doses and in plasma. Further studies need to assess ex-vivo lytic activity in plasma to allow for greater clinical translation. Conflict of interest Oshi Swarup: nothing to disclose, Joanne Chia: nothing to disclose, Zikou Liu: nothing to disclose, Tammy Lam: nothing to disclose, Anna Balabanski: nothing to disclose, Geoffrey Cloud: nothing to disclose, Bruce Campbell: nothing to disclose, Robert Medcalf: nothing to disclose