In vitro assessment of blood compatibility: Residual and dynamic markers of cellular activation

Abstract

The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension's proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.

Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation

“…The work reported here and a previous in vitro study clearly show that immobilized heparin surfaces reduce leukocyte and complement activation. 13 However, a similar result, as shown here for leukocytes and in previous work for complement activation, is not achieved by simply adding systemic heparin. 13 These observations suggest potentially significant advantages to using immobilized heparin surfaces in all blood-contacting devices; particularly for longer-term devices placed in contact with blood for days or weeks or even longer.…”

“…13 However, a similar result, as shown here for leukocytes and in previous work for complement activation, is not achieved by simply adding systemic heparin. 13 These observations suggest potentially significant advantages to using immobilized heparin surfaces in all blood-contacting devices; particularly for longer-term devices placed in contact with blood for days or weeks or even longer. A clinical study in which complement activation was shown to be unaffected by systemic heparin levels lends further support to the need for surface-bound heparin.…”

Vascular Catheters with a Nonleaching Poly-Sulfobetaine Surface Modification Reduce Thrombus Formation and Microbial Attachment

“…Human blood activation after being flowed over PICC samples was quantified as described previously (38). Briefly, after flowing blood Fig.…”

Ex vivo simulation of cardiopulmonary bypass with human blood for hemocompatibility testing

“…The latter assumption is controversial since the Carmeda bioactive surface has been shown to be stable during a two-hour period of extracorporeal circulation. 17,18…”