Complement C1q promotes primary haemostasis in a microfluidic bleeding model

In systemic inflammatory diseases, thrombotic complications often cannot be fully explained by traditional risk factors, suggesting that the immune system directly affects hemostasis. The complement system, particularly C1q (the recognition molecule of the classical complement pathway), has been shown to enhance primary hemostasis in vivo and to bind von Willebrand factor (vWF) in vitro.

To investigate the role of the C1q-vWF interaction in human primary hemostasis.

We used a microfluidic bleeding model with endothelialized microchannels to visualize hemostatic processes in real-time. Following mechanical vessel injury, we tracked C1q deposition and its colocalization with vWF, platelets, and fibrinogen using confocal microscopy. The functional relevance of C1q was assessed using the C1q-inhibitory peptide 2J.

C1q accumulates immediately at the injury site and exhibits strong colocalization with vWF and activated platelets, while colocalization with fibrinogen is minimal. Inhibiting C1q with peptide 2J significantly reduces both C1q and vWF deposition during early clot formation, and leads to prolonged bleeding time in this model.

Deposited C1q functions as a binding partner for vWF, enhancing primary hemostasis. This C1q-vWF axis may contribute to inflammation-related thromboembolic complications in humans.