Table 2:

Complement Activation and Complement Mediated Injury

Pathway	Summary & Effects	References	Key Study Details
C5a	C5a interaction with C5a receptor can lead to endothelial activation and increased release of tissue factor. C5a deposition can lead to neutrophil activation.	Redecha et al., 2007 (40) Girardi et al., 2003 (60)	-C5aR and C3aR deficient mice -Murine pregnancy model
C3, C5, C6	Deficiencies in complement components such as C3, C5, and C6 are protective from thrombophilia and endothelial activation induced by aPL.	Pierangeli et al., 2005 (42) Romay-Penabad et al., 2007 (43) Carrera-Marin et al., 2012 (44)	-Mice deficient in various complement components.
C4b-binding protein (C4BPt; inhibitor of the classical and lectin complement cascades)	C4BPt is negatively associated with complement activation products, and a sizable percentage of the reduction in C4BPt in aPL-positive patients was attributed to warfarin administration.	Grosso et al., 2021 (46)	-In vitro, patient blood
Anti-thrombin antibodies (aThr)	In patients with SLE ± APS, aTHr potentiates thrombin-mediated activation of C3 and C5.	McDonnell et al., 2022 (49)	-In vitro, patient blood
C3 and C4 (preconception levels)	Low preconception levels of C3 and C4 in APS or aPL patients are associated with a significantly higher prevalence of pregnancy loss.	Nalli et al., 2021 (50)	-In vitro, patient blood