Table 1.

Summary of intravenous hemostats and their mechanism of action.

Mechanism of Action	Class of particle or polymer	Targeting ligand(s)	References
Platelet substitutes
Binds to subendothelial matrix	Liposome	rGPIα-IIα	Nishiya et al. (2001)31
		rGPIbα	Takeoka et al. (2002)5
		vWF binding peptide (VBP): TRYLRIHPQSQVHQI Collagen binding peptide (CBP): [GPO]7*	Ravikumar et al. (2012)37
Binds to platelets	Platelet	Fixation of fibrinogen on surface using formaldehyde	Agam et al. (1983)19
	Erythrocyte	Fixation of fibrinogen on surface using formaldehyde	Agam et al. (1992)20
		Conjugation of Ac-CGGRGDF-NH2 via a heterobifunctional linker (thromboerythrocyte)	Coller et al. (1992)21
	Albumin microparticles	Surface adsorption of fibrinogen (Synthocytes™)	Levi et al. (1999)22
		rGPIα-IIα	Teramura et al. (2003)93
		Surface display of H12 peptide HHLGGAKQAGDV	Okamura et al. (2005)33–35
	Liposome	Surface display of H12 peptide HHLGGAKQAGDV	Okamura et al. (2005)32
		GSSSGRGDSPA and P-selectin binding peptide DAEWVDVS conjugated to liposomal membrane lipids	Modery et al. (2011)36
	PLL-PLGA nanoparticles	PEG arms terminated with GRGDS conjugated to NP surface	Bertram et al. (2009)41
Binds to subendothelial matrix and platelets	Liposome	Extraction and incorporation of platelet membrane proteins including GPIbα, GPIIb-IIIα, and GPIV/III into the liposomal membrane (plateletsome)	Rybak et al. (1993)29
		Surface display of VBP, CBP, and fibrinogen mimetic peptides (i.e. cyclo-CNPRGDY(OEt)RC or GRGDS)	Ravikumar et al. (2012)38 Modery-Pawlowski et al. (2013)39 Anselmo et al. (2014)45
Binds to and activates platelets	Lipsomes	H12 peptide-coated liposomes encapsulating ADP	Okamura et al. (2009)40
Fibrin modulators
Crosslinks fibrin	Ultra-low crosslinked p(NIPAm)-AAc microgels	Fibrin-binding sdFvs conjugated to the surface of ~1 μm-diameter microgel particles (platelet-like particles)	Brown et al. (2014)91
	Poly(HEMA)	Fibrin-binding peptides (Ac- Y(DGl)C(HPr)YGLCYIQGK-Am*†) grafted onto a linear poly(HEMA) backbone (polySTAT)	Chan et al. (2015)88

^*O and HPr = hydroxyproline; DGl = D-glutamic acid; Ac = acetylation; Am = amidation.

^†Cyclized via C3 and C8 residues.