A Positively Charged Surface Triggers Coagulation Activation Through Factor VII Activating Protease (FSAP)

Area of Science:

• Biomaterials Science
• Hemostasis and Thrombosis
• Surface Chemistry

Background:

• Biomaterial contact with blood can trigger adverse coagulation and inflammation.
• Coagulation on negatively charged materials involves Factor XII, but cationic surface mechanisms remain unclear.

Purpose of the Study:

• Investigate Factor VII activating protease (FSAP) interaction with charged biomaterials.
• Determine FSAP's role in surface-initiated blood coagulation.

Main Methods:

• Assessed FSAP activation on biomaterial surfaces with varying charges (PEI, PLL, glass, SAM-COOH, Teflon AF).
• Measured thrombin and fibrin formation in whole blood incubated on these surfaces.
• Utilized contact phase inhibitors and FSAP inhibitory antibodies to elucidate coagulation pathways.

Main Results:

• FSAP exclusively activated on positively charged surfaces (PEI, PLL).
• Coagulation on PEI was FSAP-dependent, unlike other surfaces where Factor XII was implicated.
• FSAP inhibition significantly reduced coagulation markers on PEI surfaces.

Conclusions:

• FSAP activation represents a novel mechanism for surface-driven blood coagulation.
• Targeting FSAP may improve the hemocompatibility of cationic biomaterials for clinical use.