Blood response to biomaterials : in vitro and clinical investigation of the contact phase of blood coagulation

Awarding institution
  • University of Strathclyde
Date of award
  • 1995
Thesis identifier
  • T8672
Qualification Level
Qualification Name
Department, School or Faculty
  • The clinical utilisation of materials and devices involving contact with blood, has promoted a growing interest in blood-biomaterial interactions and monitoring of the blood response. This study focused on the establishment of a parameter relevant for the measurement of contact phase activation of blood coagulation and its suitability for in vitro and clinical evaluation. The selected biomaterials for in vitro assessment were commercially available haemodialysis membranes and the selected clinical procedures were haemodialysis (HD) and cardiopulmonary bypass (CPB). In vitro measurements were considered in relation to membrane charge and adsorption of FXII and heparin. Three methods for determining contact activation, based on measurement of factor XII activity, were investigated. A factor Xll-like activity (FXIIA) was measured by a modified chromogenic substrate assay. FXIIA was determined in vitro in the plasma supernatant and on the membrane surface following blood-membrane contact. Supernatant values of FXIIA did not discriminate between membranes but surface values were related to membrane structure and the presence of pharmacological agents. Factor XII activity (FXIIa) was measured by an enzyme immunoassay and FXIIa values in plasma were determined in vitro.Measurement of FXIIa improved the detection sensitivity and provided some degree of discrimination. Factor XIIa/FXIIa-inhibitor complexes were measured by a developed ELISA assay and values obtained in vitro and during HD and CPB. Enhanced sensitivity was demonstrated in vitro and clinical levels were related to the disease state and membrane type in HD and the treatment period and the presence of aprotinin in CPB. The evidence suggests that FXIIA measured on the membrane surface was more relevant to biomaterials evaluation than the supernatant measurement. FXIIa assay was relatively more sensitive than the chromogenic substrate assay in terms of the supernatant measurements. The FXIIa/XHa-inhibitor complexes assay provided a better discrimination between materials and therefore is recommended as an appropriate parameter for monitoring theinfluence of biomaterials, devices and pharmacological agents in clinical applications.
Resource Type
Date Created
  • 1995
Former identifier
  • 995002113402996