Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease

Thromb Res. 2015 Sep;136(3):625-33. doi: 10.1016/j.thromres.2015.07.027. Epub 2015 Jul 30.

Abstract

Introduction: Von Willebrand disease (vWD) is the second least common hemostatic disorder in Malaysia, and it has a low prevalence. This study examined the underlying platelet thrombogenicity cascades in the presence of different formulations of chitosan-derivatives in vWD patients. This paper aimed to determine the significant influence of chitosan biomaterial in stimulating the platelet thrombogenicity cascades that involve the von Willebrand factor, Factor 8, Thromboxane A2, P2Y12 and Glycoprotein IIb/IIIa in vWD.

Materials and methods: Variable chitosan formulations of N,O-Carboxymethylchitosan (NO-CMC) and Oligo-Chitosan (O-C) were tested. Fourteen vWD subjects voluntarily participated in this study after signing informed consent forms. The patient's demographic profiles, family history, type of vWD, clinical symptoms and laboratory profiles were recorded and analyzed. Enzyme-linked immunosorbent assay, flow cytometry and Western blot tests were used to determine the level of the chitosan-adhered-platelet-mechanisms.

Results: The study revealed that most patients were predominantly affected by vWD type I. The O-C group of chitosan's scaffold pores is sufficient to allow for nutrients and cells. The O-C-stimulated-mediators are capable of initiating the platelet actions and were detected to expedite the blood coagulation processes. The oligo-group of chitosans was capable of amplifying and triggering more platelet activator's pathways via the studied mediators. The present findings suggest that the ability of each type of chitosan to coagulate blood varies depending on its chemical composition.

Conclusion: The oligo group of chitosans is potentially capable of triggering platelet thrombogenicity cascades by activating platelets in vWD patients to form a platelet plug for hemostasis process.

Keywords: Hemostasis; N,O-Carboxymethylchitosan (NO-CMC); Oligo-Chitosan (O-C); Platelet mechanisms; Von Willebrand disease (vWD).

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Platelets / drug effects*
  • Chitin / administration & dosage
  • Chitin / analogs & derivatives*
  • Chitosan / administration & dosage
  • Chitosan / analogs & derivatives*
  • Drug Implants
  • Female
  • Hemostatics / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Oligosaccharides
  • Platelet Activation / drug effects
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Treatment Outcome
  • Young Adult
  • von Willebrand Diseases / blood*
  • von Willebrand Diseases / drug therapy*

Substances

  • Drug Implants
  • Hemostatics
  • Oligosaccharides
  • carboxymethyl-chitosan
  • oligochitosan
  • Chitin
  • Chitosan