Understanding Platelet Thrombogenicity Cascade Of The Biodegradable Chitosan Derivatives In Von Willebrand Disease In Vitro

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dc.contributor.authorPERIAYAH, MERCY HALLELUYAH
dc.date.accessioned2017-09-06T01:22:12Z
dc.date.available2017-09-06T01:22:12Z
dc.date.issued2015-11
dc.description.abstractChitosan has become one of the most promising local hemostatic agents because it is of particular interest as it functions independently on platelets and normal clotting mechanisms. The present study was designed with the aim to test the ability of the mechanisms of blood platelets towards the action of biodegradable chitosan in normal donors and von Willebrand disease (vWD) patients in vitro. This work determined the underlying mechanism of chitosan-induced platelet thrombogenicity and comprises experimental tests such as degradation ability; platelet: adhesion, activation: aggregation; coagulation analysis and hemostatic mediators: von Willebrand Factor (vWF), Factor 8 (FVIII), Thromboxane A2 (TXA2), P2Y12, glycoprotein IIbIIIa (GpIIbIIIa), Transforming Growth Factor- Beta 1 (TGF-β1) and Platelet Derived Growth Factor-AB (PDGF-AB). Comparative studies have been conducted to measure the hemostatic capacity of biodegradable 7% N,OCarboxymethylchitosan (NO-CMC) (with 0.45 mL collagen), 8% NO-CMC, Oligochitosan (O-C) and O-C 53. Lyostypt, the topical hemostatic agent was used as a positive control. This study was conducted using enzyme-linked immunosorbent assay, westergren, coagulation analyzer, platelet aggregometery, western blotting, flow cytometry, scanning electron microscopy, light microscopy and automated hematology analyzer techniques. Fourteen vWD and normal donors were recruited in xxx this study with provided informed written consent. O-C type of chitosans are able to enzymatically degrade and possess better porosity to allow nutrients and cells to enter to accelerate hemostasis and wound healing process. O-Cs exert a combined effect on thrombogenesis by causing platelets to adhere, activate, aggregate and forms fibrin network to strengthen platelet plug formation by elevating the studied mediators. O-C was capable to induce the expression levels of vWF and FVIII antigenicity and TXA2 receptor signals. This signaling pathway assists the platelet aggregation. Also, GpIIbIIIa and P2Y12 analysis showed that O-C group of chitosan are capable of activating platelets by providing a good surface for blood hemostatic mediators and signals to facilitate thrombin generation. O-C-activated platelets lead to the release of growth factors, mainly TGF-β1 and PDGF-AB. Therefore, this exhibited that greater expression level of O-C group of chitosan assists in mediating wound healing process. vWD is the low prevalence hereditary bleeding disorder occurs in Malaysia, and most patients belong to vWD type I. Oligo group of chitosans are potentially capable to trigger platelet thrombogenicity cascades in vWD patients. Tested chitosan-stimulated-mediators potentially initiate the platelet actions and thus expedite the hemostatic processes via 3 major processes: platelet adhesion, activation and aggregation. This study demonstrated that the greater expression level of O-C assists in elevating platelet thrombogenicity cascades to achieve hemostasis. Biodegradable O-C and O-C 53 type of chitosan worked better than NO-CMC types of chitosan in activating platelet activities to form the hemostatic plug in normal donors and vWD patients in vitro.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/4466
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectPlatelet Thrombogenicity Cascadeen_US
dc.subjectOf The Biodegradableen_US
dc.titleUnderstanding Platelet Thrombogenicity Cascade Of The Biodegradable Chitosan Derivatives In Von Willebrand Disease In Vitroen_US
dc.typeThesisen_US
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