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Decreased Clot Burden is Associated with Factor XIII Val34Leu Polymorphism and Better Functional Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

I. Szegedi1, R. Orbán-Kálmándi2, A. Nagy3, F. Sarkady2, N. Vasas4, M. Sik4, L. Lánczi4, E. Berényi4, L. Oláh1, L. Csiba5, Z. Bagoly6

1University of Debrecen, Faculty of Medicine, Department of Neurology, Debrecen, Hungary, 2University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Laboratory Sciences, Debrecen, Hungary, 3University of Debrecen, Faculty of Public Health, Department of Preventive Medicine, Debrecen, Hungary, 4University of Debrecen, Faculty of Medicine, Department of Radiology, Debrecen, Hungary, 5University of Debrecen, Faculty of Medicine, Department of Neurology, MTA-DE Cerebrovascular and Neurodegenerative Research Group, Debrecen, Hungary, 6University of Debrecen, Faculty of Medicine, Department of Laboratory Medicine, , Division of Clinical Laboratory Sciences, MTA-DE Cerebrovascular and Neurodegenerative Research Group, Debrecen, Hungary

Abstract Number: LPB0066

Meeting: ISTH 2021 Congress

Theme: Fibrinogen, Fibrinolysis and Proteolysis » Thrombolytic Therapy

Background: Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO).

Aims: Here we aimed to evaluate how thrombus burden affects the outcome of the intravenous thrombolysis and studied the association between a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS), and various fibrinolysis parameters.

Methods: In this single-centered, prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0-9) were matched with 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII activity, and D-dimer were assessed from blood samples taken on admission and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA imaging. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event.

Results: Poor outcomes were significantly more frequent in the CBS 0-9 group. Plasminogen activity on admission was significantly higher in the CBS 0-9 group. In a univariate analysis, a significant protective effect of the Leu34 allele against developing larger clots (CBS 0-9) could be demonstrated (OR:0.519; 95%CI:0.298-0.922, p=0.023). Multivariate regression analysis revealed that larger thrombus burden (CBS 0-9) is an independent predictor of short- and long-term functional outcomes (mRS 3-6: OR: 2.5; 95%CI:1.179-5.306, p=0.017) while such effect of the studied fibrinolysis parameters could not be demonstrated.

Conclusions: CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.

To cite this abstract in AMA style:

Szegedi I, Orbán-Kálmándi R, Nagy A, Sarkady F, Vasas N, Sik M, Lánczi L, Berényi E, Oláh L, Csiba L, Bagoly Z. Decreased Clot Burden is Associated with Factor XIII Val34Leu Polymorphism and Better Functional Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/decreased-clot-burden-is-associated-with-factor-xiii-val34leu-polymorphism-and-better-functional-outcomes-in-acute-ischemic-stroke-patients-treated-with-intravenous-thrombolysis/. Accessed August 15, 2022.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/decreased-clot-burden-is-associated-with-factor-xiii-val34leu-polymorphism-and-better-functional-outcomes-in-acute-ischemic-stroke-patients-treated-with-intravenous-thrombolysis/

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