FVII Dependent Coagulation Activation in Citrated Plasma by Polymer Hydrogels

Abstract

Polymer hydrogels containing positively charged functional groups were used to investigate the critical material and biological components of FVII activation and subsequent fibrin formation in citrated plasma. A FVIIa ELISA confirmed the ability of the polymer to induce FVII activation and provided insight into the material parameters which were influential in this activation. Experiments utilizing coagulation factor depleted and inhibited plasmas indicated that FVII, FX, FII, and FI are all vital to the process outlining the general mechanism of fibrin formation from the onset of FVII activation. Dynamic mechanical analysis and swelling experiments were used to establish a critical correlation between polymer microstructure and FVII activation.

Hemostatic strategies for traumatic and surgical bleeding

“…Electrostatic charge of the DMAEMA‐based functional groups likely dictates the function of these materials. The effect of electrostatic charge on secondary hemostasis was also demonstrated by a primary amine containing synthetic polymer hydrogel that induced FVII activation in vitro . Similar cationic hydrogels exhibited high swelling and hemostatic ability in vitro and in vivo .…”

“…The effect of electrostatic charge on secondary hemostasis was also demonstrated by a primary amine containing synthetic polymer hydrogel that induced FVII activation in vitro. 95 Similar cationic hydrogels exhibited high swelling and hemostatic ability in vitro and in vivo. 100,101 Synthetic polymers with mechanisms that directly target primary and secondary hemostasis are increasingly prevalent features of hemostatic agents.…”

“…More recently, synthetic materials have been designed to target platelet activation and aggregation in primary hemostasis, 93,94 clotting factor activation, 95,96 and red blood cell aggregation to promote clot formation. 97,98 Platelet activation and aggregation can be indicative of hemostatic potential.…”

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding

“…The hemostatic ability of this material was attributed to its capacity of absorbing high amount of fluids from the wound and expanding to exert a mechanical tamponade effect on the wound. Casey et al have recently reported on the development of a series of cationic acrylamide hydrogels that demonstrated the capability of activating coagulation factors that may aid in clot formation and hemostasis . Another tissue sealant technology based on albumin‐glutaraldehyde (e.g., BioGlue, CryoLife Inc., Georgia, USA), is available in the United States for surgical adhesive applications in open surgical repair of large vessels (such as aorta, femoral, and carotid arteries) .…”

- Plasma Immunoglobulins

“…87 Bivalirudin (Angiomax) started life as hirugen 88 with Biogen and is currently a product of The Medicines Company. [127][128][129][130][131][132][133][134][135][136][137] Another complication is provided by the intrinsic catalytic activity Downloaded by [New York University (NYU)] at 10:11 11 September 2016 of the zymogen (factor VII) form, *,138 resulting in the observation of relatively small increases in activity on activation. [89][90][91][92][93] Factor VII (proconvertin) was first described by Alexander and coworkers.…”