P055 - Development of a Human Blood ex-vivo Model for the Testing of Haemocompatibility of Vascular Access Devices

Ryan McKinnon, MMedRes - Research Assistant, Griffith university
Melissa Grinter, BBioMedSci - Research Assistant, Griffith university
Caitlin Ryan, N/A - Research Assistant, Griffith University
Andrew Bulmer, PhD - Professor, Griffith University

Purpose: : Vascular access devices (VADs) occlude due to blood interaction and thrombus formation. Fit-for-purpose testing methods of VAD materials would provide more accurate data regarding haemocompatibility during development. We developed a method for testing human blood interaction with two PICC materials (polyurethane and surface modifying macromolecules (SMMs)) to assess haemocompatibility.

Methods: : Citrated whole blood was collected from five healthy human donors. Full blood count (FBC) was performed to determine participants blood cell and platelet profiles. Whole blood was then aliquoted into Eppendorf tubes and incubated with PICC lines of differing polymer compositions. Samples were incubated for two hours on a rocker at 30 rpm at 37°C to simulate in-vivo conditions. The PICC lines were then removed and placed in fixative for analysis via scanning electron microscopy (SEM). Blood interaction with PICC materials was assessed semi-quantitatively by assessing differences in protein deposition, erythrocyte, platelet and fibrin adhesion. The remaining blood sample was analysed for FBC, thromboelastometry, coagulability, clotting proteins and haemolysis contributing to the requirements of ISO 10993:4 testing.

Results: : The surface of the PICC materials were markedly different in their texture and roughness when analysed using SEM. Qualitative analysis of the PICC lines demonstrated a visible film of plasma protein adhered to the polymer surface. Adherence of platelets and platelet bundles were assessed semi-quantitatively and bound similarly to both PICC materials. However, a significant reduction in the number of erythrocytes were bound to the surface of the modified PICCs. This corresponded with an increase in erythrocytes and platelet numbers, analysed by FBC, from the remaining blood sample. The use of viscoelastic and coagulation testing further revealed the potential on the sample to form thrombi. Testing of individual clotting factors proved useful in understanding the relationship between SMM treated polymers and their potential anti-thrombogenic properties.

Limitations:: The developed method permits the testing of patient blood samples, including blood that may contain medications, or encourage responses to foreign materials. However, limitations include that the blood analysed remained anti-coagulated and did not experience physiological conditions as would be observed in-vivo.

Conclusions: : This model represents an improvement over current testing methods of haemocompatibility that apply animal blood for early-stage product development. The data and model presented here will therefore facilitate early testing of human blood and device hemocompatibility/thrombogenicity, which more closely predict responses in-vivo. Improving the accuracy of early phase testing will expedite product development and approval. Early evidence presented here suggests that modification of VAD polymers may reduce thrombogenicity and improve haemocompatibility. These data suggest that state-of-the-art polymer modification have the potential to reduce complications including thrombosis, VAD failure, morbidity and mortality in addition to improving clinical efficiency.