Hemostasis in the Era of the Chronic Anticoagulated Patient
- Volume 15 - Issue 1 - January, 2004
- Posted on: 8/1/08
- 0 Comments
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The technology to produce poly-N-acetylglucosamine (pGlcNAc) polymer is based on a biomaterial that is derived in a fiber form from aseptic cultures of a marine microalgae diatom. Once isolated and purified, the high quality, pure material is subject to rigorous quality control and quality assurance. The end product can be formulated as patches, lyophilized patches, gels, microspheres, and foams. The isolation of pGlcNAc fibers provides the source of the material for the manufacture of the Syvek Patch® (Marine Polymer Technologies, Danvers, Massachusetts). The ability of this material to provide hemostatic action is a very specific property of the way the polymer is organized in the pGlcNAc fibers (Figure 1).
Hemostasis is defined as the process through which the body controls vascular injury and bleeding from it. Hemostasis has three inter-related components: vasoconstriction, red blood cell functions and platelet/coagulation factor activation. Examples of red blood cell function include rheology, during which red blood cells direct platelets toward the endothelium, and also release of certain paracrine-like receptors from red blood cells.
Manual compression alone takes approximately 20 to 30 minutes to control bleeding from a diagnostic procedure and up to 60 minutes for an interventional procedure. These times are dramatically reduced to 5 and 10 minutes with a pGlcNAc patch. pGlcNAc provides hemostasis through mechanisms that involve vasoconstriction, red blood cell agglutination and platelet activation.
Vasoconstriction. A series of studies conducted by Ikeda et al.1 utilized an aortic ring model where one of the metrics was the ability of these in-vitro rings to generate force. They titrated these rings with increasing concentrations of pGlcNAc and achieved a dose-dependent generation of force corresponding to a vasoconstrictive effect. They found that when the endothelium was denuded, this vasoconstrictive effect was ablated. Thus, it is an endothelium-dependent vasoconstriction. They sought to determine if the pGlcNAc affected the nitric oxide (NO) signal by looking at NO generation from these rings. They found that the presence or absence of the pGlcNAc did not affect the generation of that messenger. Then they examined the role of endothelin-1 in this system by looking at an inhibitor of the endothelin-1 receptor. They found that if this inhibitor was added, the result was partial ablation of the pGlcNAc-induced vasoconstriction. The sum of what is known today in this area is essentially that the vasoconstrictive process is in part mediated by the messenger endothelin-1.
Red blood cell agglutination. Figure 2 shows a histological section from a hemorrhaging spleen where the pGlcNAc patch was placed on a wound. Agglutination of red blood cells is visible on the patch. At a scanning electron micrographic level, the red blood cells appear in an altered morphology. A fiber nest forms over the red blood cells. Although the exact mechanism of this altered morphological agglutination is unknown, it could be a change in the membrane potential in the cells and/or an osmotic effect on the cells.
Platelet activation. In an experiment where platelets were allowed to contact pGlcNAc fibers, a morphological change of the platelet that is characteristic of a full-blown activation response was seen (Figure 3). As Figure 3 demonstrates, the pseudopodia make a robust contact with the pGlcNAc.