Understanding Platelet Thrombogenicity Cascade Of The Biodegradable Chitosan Derivatives In Von Willebrand Disease In Vitro
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Date
2015-11
Authors
PERIAYAH, MERCY HALLELUYAH
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Chitosan 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
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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.
Description
Keywords
Platelet Thrombogenicity Cascade , Of The Biodegradable