OC 34.4 - Association of NETS and inflammation biomarkers with clinical outcome in patients with acute ischemic stroke undergoing thrombectomy: does heparin treatment modify this?

Monday, June 24, 2024

10:15 – 10:30 ICT

Room: Ballroom B4

Presenting Author(s)

Aarazo Barakzie, MSc

MSc. Ph.D. student
Erasmus MC
Rotterdam Zuid Holland, Zuid-Holland, Netherlands

Co-Author(s)

Wv

Wouter van der Steen

Dr. MD. PhD, Trainee neurology
Erasmus MC
Rotterdam Zuid Holland, Zuid-Holland, Netherlands
AJ

A. J. Gerard Jansen

Internist Hematologist
Erasmus MC
Rotterdam Zuid Holland, Zuid-Holland, Netherlands
BR

Bob Roozenbeek

Dr. MD. neurologist, associate professor
Erasmus MC
Rotterdam Zuid Holland, Zuid-Holland, Netherlands
AV

Aad Van Der Lugt

Dr. Prof. Radiologist
Erasmus MC
Rotterdam, Zuid-Holland, Netherlands
DW

Diederik W.J. Dippel

Dr. MD. PhD. neurologist
Erasmus MC
Rotterdam, Zuid-Holland, Netherlands
Hugo ten Cate, MD, PHD

MD, PhD
Departments of Internal Medicine and Biochemistry, Maastricht University Medical Center+, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
Moniek de Maat

Professor, MSc, PhD
Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Patients with acute ischemic stroke (AIS) are treated with thrombectomy (EVT). Recently, the MRCLEAN-MED randomized trial studied whether unfractionated heparin during endovascular thrombectomy (EVT) had a beneficial effect on functional outcome. We postulated that biomarkers of NETosis (Neutrophil Extracellular Traps) and inflammation might affect outcome, and that heparin during EVT may improve treatment efficacy by decreasing NETosis and inflammation.

Aims: To study the impact of periprocedural heparin on neutrophil activation and NETosis after EVT for AIS, and thereby their association with clinical outcome.

Methods: We studied 315 AIS patients from the MRCLEAN-MED who were randomized to receive moderate-dose heparin (5000 IU bolus followed by 1250 IU/hour for 6 hours, n=21), low-dose heparin (5000 IU bolus followed by 500 IU/hour for 6 hours, n=150) during EVT or no heparin (n=144) and had blood samples taken on admission, 1h and 24h after reperfusion. Selected biomarkers, including NETs (MPO-DNA, Histone-DNA, Citrullinated histone H3) and C-reactive protein (CRP) were measured and correlated with 90 days outcome measured with the post-event modified Rankin Scale (mRS), using logistic regression.

Results: APTT ratio (Fig.1) and Anti-Xa levels (Median:0.67 IU/mL [25th–75th percentiles:0.25-1.05 ]) documented the presence of heparin use. At 1h after EVT alone, levels of MPO-DNA and Histone-DNA complexes were significantly decreased compared to before EVT. At 1h and 24h, CRP levels were increased compared to levels at admission. However, after heparin+EVT, MPO-DNA levels were similar at all time points, and at 1h after heparin+EVT, Histone-DNA levels were significantly decreased. Only, at 24h after Heparin+EVT, CRP levels were increased compared to levels before EVT (Fig.1). There was no significant association between these biomarkers and functional outcome.

Conclusion(s): Although heparin attenuated systemic inflammation early after EVT, there was no consistent impact of heparinisation on neutrophil activation and no association of inflammation and NETosis with clinical outcome.