PB0718 - Complement Inhibition Reduces Fibrin Formation and Platelet Activation During Haemostasis in a Microfluidic Bleeding Model

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

MG

Murielle Golomingi

PhD Student
University of Bern
Bern, Bern, Switzerland
JK

Jessie Kohler

MD student
University of Bern
Bern, Bern, Switzerland
CL

Christina Lamers

Senior Scientist
University of Basel
Basel, Basel-Stadt, Switzerland
RP

Richard Pouw

Senior Scientist
University of Basel
Basel, Basel-Stadt, Switzerland
DR

Daniel Ricklin

PI, Research Group Leader
University of Basel
Basel, Basel-Stadt, Switzerland
JD

József Dobó

PI, Research Group Leader
Research Centre for Natural Sciences
Budapest, Budapest, Hungary
PG

Péter Gál

PI, Research Group Leader
Research Centre for Natural Sciences
Budapest, Budapest, Hungary
GP

Gábor Pál

PI, Research Group Leader
Eötvös Lorand University
Budapest, Budapest, Hungary
BK

Bence Kiss

Senior Scientist
Eötvös Lorand University
Budapest, Budapest, Hungary
Elaissa Trybus Hardy, PhD

Senior Scientist
Department of Pediatrics, Emory University School of Medicine, USA
Atlanta, Georgia, United States
WL

Wilbur Lam

PI, Research Group Leader
Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and Department of Pediatrics; Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering
Atlanta, Georgia, United States

Presenting Author(s)

Verena Schroeder, PhD

Research Group Leader, PI, Study Director for the Master in Pharmacy
University of Bern
Bern, Bern, Switzerland

Background: Interactions between the complement system and coagulation and fibrinolysis contribute to thrombosis, in particular in an inflammatory environment. Whether the complement system also affects coagulation during the haemostatic response to vascular injury and bleeding, is not yet known.

Aims: To investigate the effects of complement inhibition on fibrin formation and platelet activation upon vascular injury in a microfluidic bleeding model.

Methods: In a microfluidic bleeding model featuring endothelial cells and perfusion with fresh human whole blood, clot formation was detected by fibrin deposition and platelet activation (CD62P) at the injury site and monitored over time with a confocal microscope. We studied the effects of inhibitors targeting complement activation on different levels of the complement system: classical pathway (C1s), lectin pathway (MASP-1, MASP-2), alternative pathway (FD), and common pathway (C3, C5).

Results: Among the inhibitors targeting individual complement activation pathways, a significant reduction of fibrin formation was only observed in the presence of the MASP-1 inhibitor, and platelet activation was reduced in the presence of the MASP-1 inhibitor and the FD inhibitor. Both common pathway inhibitors targeting C3 or C5, respectively, were associated with a substantial reduction of fibrin formation, and platelet activation was also reduced in the presence of the C3 inhibitor. When the inhibitors were directly compared in a single experiment, the C5 inhibitor had the strongest effect on fibrin formation, while the FD and C3 inhibitors had the strongest effect on platelet activation.

Conclusion(s): Our results show that complement inhibition, in particular when targeting the common pathway, reduces fibrin clot formation and platelet activation and suggest a role of the complement system in haemostasis. Bleeding complications as potential side effects of anti-complement therapies should be taken into consideration and evaluated in clinical studies.