Contact Activation of Blood-Plasma Coagulation

Open Access
Author:
Diggs, Tanisha
Graduate Program:
Materials Science and Engineering
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
July 16, 2008
Committee Members:
  • Erwin A Vogler, Thesis Advisor
Keywords:
  • plasma
  • coagulation
  • FXII
  • FXIIa
  • FXIIf
  • contact activation
  • blood
  • hemocompatible biomaterials
Abstract:
Initiation of the coagulation cascade ultimately leads to thrombus (clot) formation. This phenomenon impedes the production of hemocompatible biomaterials. Adverse reactions at the interface of a biomaterial in contact with the biological system, in this instance blood, start the contact activation mechanism. Upon initiation, blood-plasma coagulation proceeds through a sequence of zymogen-enzyme conversions; the complexity of this succession can quickly amplify into thrombus formation. Therefore, future innovation of cardiovascular biomaterials insists on additional information regarding blood-biomaterial interactions. In-vitro plasma coagulation assays, chromogenic assays and contact activation experiments establish dose-response relationships seeking to relate thrombogenicity to material properties. This thesis work utilizes these assays in attempt to better understand surface mediated bio-interactions. FXII is initially an inactive enzyme, also called a zymogen, activated in the contact activation mechanism by contact with a surface. The subsequent activation of FXIIa and/or FXIIf are two possible outcomes following contact activation. Results from this thesis proves contact activation yield at hydrophobic surfaces in neat FXII solution was greater than hydrophilic surfaces in neat FXII solution by plasma coagulation assay and by chromogenic assay. Additionally, this thesis provides evidence that FXIIf has procoagulant activity as well as amidolytic activity that can activate the intrinsic pathway. Prior research suggests autohydrolysis is a significant reaction in the FXIIa chromogenic assay. This thesis confirms the same results; however, results reported herein confirm that authohydrolysis is not a significant reaction in the FXIIf chromogenic assay. Additionally, plasma coagulation assays show that FXIIf is 2.6 times weaker procoagulant than FXIIa on a molar basis.