Coagulation Factor XII Levels and Intrinsic Thrombin Generation in Multiple Sclerosis

Area of Science:

• Coagulation cascade and hemostasis
• Neuroimmunology and autoimmune diseases
• Biomarker discovery in neurological disorders

Background:

• Factor XII (FXII) initiates the intrinsic coagulation pathway.
• FXII is implicated as a potential autoimmunity mediator in multiple sclerosis (MS).
• Elevated FXII activity and central nervous system depositions are observed in MS patients.

Purpose of the Study:

• To quantify FXII protein levels and pro-coagulant activity in MS patients.
• To analyze the temporal variations of FXII-related variables in MS.
• To explore FXII activation kinetics in thrombin generation (TG) within the context of MS.

Main Methods:

• Assessed FXII procoagulant activity (FXII:c) and FXII antigen (FXII:Ag) in 74 MS patients and 49 healthy subjects (HS).
• Calculated FXII ratio (FXII:ratio) and evaluated intrinsic thrombin generation using various triggers.
• Analyzed FXII variables over four time points to assess disease correlation.

Main Results:

• MS patients exhibited higher FXII:Ag levels (p=0.003) and lower FXII:ratio (p<0.001) compared to HS.
• Significant temporal differences were observed for FXII:c (p=0.031).
• Intrinsic TG triggered by nucleic acid addition showed increased ETP (p=0.004) and TG peak height in MS patients, suggesting reduced FXII activation response.

Conclusions:

• MS patients present with elevated FXII protein levels and diminished FXII function in the intrinsic coagulation pathway.
• These findings highlight a potential role for FXII in MS pathogenesis and progression.
• Further investigation using diverse methodologies is warranted to elucidate FXII's contribution to MS.