Hemostasis in the Era of the Chronic Anticoagulated Patient

Unique structure of polymer in the pGlcNAc patch.
Splenic injury cross section demonstrating the interaction of red blood cells with pGlcNAc. The pGlcNAc causes rapid red blood cell aggregation.
Scanning electron micrograph demonstrating platelets contacting the pGlcNAc patch fibers.
Fluorescence and phase micrograms demonstrating platelets binding to and activating on the pGlcNAc patch fibers.
GPIIb/IIIa complex assumes an activated conformation upon contact with NAG.
pGlcNAc activates a Ca signal in platelets.
 pGlcNAc induces surface exposure of PS.
Scanning electron microgram showing platelets on the pGlcNAc.
Author(s): 

Bonnie Weiner, MD, *Thomas Fischer, PhD, †Sergio Waxman, MD


Physical structure of the pGlcNAc fiber. In a series of experiments, plasma containing platelets was incubated with three different materials and a control (no material added). The materials tested included pGlcNAc, Chito-Seal topical hemostasis pad (Abbott Vascular Devices, Redwood City, California) and Clo-Sur pad (Scion Cardio-Vascular, Miami, Florida). Chito-Seal, Clo-Sur pad and control all produce a clot in 20 minutes. Only the purified pGlcNAc fibers were able to reduce clotting time to 10 minutes.
The physical structure of the pGlcNAc fibers is important. Figure 8 shows activated platelets on a mesh of pGlcNAc fibers. Everything is sized so the platelets can intercalate with the fibers in an intimate fashion. Once fibrin polymerization begins, nucleated at these platelets, the result is a tertiary mesh because the fibrin can polymerize within that mesh to interlace with it. In contrast, the Clo-Sur product presents a plainer sheath to the platelets. It contact activates them, but there is no intimate physical interaction with the material. Similarly, the Chito-Seal product produces long tubular structures. They contact activate the platelets, but again, there is no close interaction.
In summary, when blood contacts the pGlcNAc matrix, the first event to occur on a time scale of nanoseconds to microseconds is a chemical-physical absorption of serum proteins to the matrix. These serum proteins are in an altered conformation, particularly fibrinogen. The platelets recognize the altered conformation and stimulate an activation response. The coagulation cascade activates, the red blood cells agglutinate and generate thrombin and a fibrin mesh is synthesized in the microenvironment of the pGlcNAc patch. At this point, the platelets generate force through the clot retraction process, and the vasoconstrictive effects augment a mechanical constriction.
In terms of what is occurring in the clinic, the platelet/pGlcNAc/red blood cell/fibrin mesh forms a hemostatic plug that creates stagnant blood in the track. Three conditions, the triad of conditions needed for thrombus formation, are now operant: injured tissue, static blood, and a procoagulative state of blood that is driven by the presence of the activation complex on the patch.

Clinical Experience with pGlcNAc



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