Saad, Arman Zaharil Mat
(2016)
Understanding platelet thrombogenicity
cascade of the biocompatible chitosanderivates
in von willebrand disease.
Technical Report.
Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia.
(Submitted)
Abstract
Introduction: Chitosan extracted from the shells of arthropods have becoming one of the most
promising local hemostatic agents because it is of particular interest as it functions independently on
platelets and normal clotting mechanisms. Objectives: This work verified the underlying
mechanisms of chitosan-induced platelet thrombogenicity cascades and comprises experimental tests
such as degradation ability; coagulation analysis and the investigations of hemostatic mediators: von
Willebrand Factor (vWF), Factor 8 (FVIII), Thromboxane A2 (TXA2), P2Yl2, glycoprotein IlbIIIa
(GpIIbIIIa), Transforming Growth Factor- Beta 1 (TGF-~1) and Platelet Derived Growth Factor-AB
(PDGF-AB) in normal donors and von Willebrand disease (vWD) patients in vitro. Materials and
Methods: Comparative studies have been conducted to measure the hemostatic capacity of
biodegradable: 7% N,O-Carboxymethylchitosan (NO-CMC) (with 0.45 mL collagen), 8% NOCMC,
Oligo-chitosan (0-C) and 0-C 53. Lyostypt, the topical hemostatic agent was used as a
positive control. This study was conducted using scanning electron microscope, enzyme-linked
immunosorbent assay, westergren, coagulation analyzer, western blotting and flow cytometry
techniques. Fourteen vWD and normal subjects were recruited in this study with provided informed
written consent. Results and Discussions: 0-C type of chitosans are able to enzymatically degrade, 1
possess better porosity and the scaffold pores are sufficient to allow nutrients and cells to enter and
by encouraging platelet activities to accelerate hemostasis and wound healing process. 0-Cs exert a
combined effect on thrombogenesis by causing platelets to adhere, activate, aggregate and forms
insoluble fibrin network to strengthen platelet plug formation by elevating the studied mediators.O-C
was capable to induce the expression levels of vWF, FVIII and TXA2 receptor signals. This
signaling pathway assists the platelet aggregation. Also, GpIIbIIIa and P2Y 12 analysis showed that
0-C group of chitosan are capable of activating platelets by providing a good surface for blood
hemostatic mediators and signals to facilitate thrombin generation. 0-C-activated platelets lead to
the release of growth factors, mainly TGF-~1 and PDGF-AB. Therefore, this exhibited that greater
expression level of 0-C group of chitosan assists in mediating wound healing process. Conclusion:
Tested chitosan-stimulated-mediators potentially initiate the platelet actions and expedite the
hemostasis processes in vitro. Based on the outcome of this research, the 0-C and 0-C 53 stimulated
hemostasis process and worked better and equal to the commercially available lyostypt in normal
donors or subjects and vWD patients in vitro.
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