title: Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Electronic address: jr.mercy@yahoo.com.
authors.forename: Mercy Halleluyah
authors.initials: MH
authors.lastname: Periayah
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Electronic address: ashalim@usm.my.
authors.forename: Ahmad Sukari
authors.initials: AS
authors.lastname: Halim
authors.affiliation: Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Electronic address: armanzaharil@gmail.com.
authors.forename: Arman Zaharil
authors.initials: AZ
authors.lastname: Mat Saad
authors.affiliation: Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Electronic address: soriani@usm.my.
authors.forename: Nik Soriani
authors.initials: NS
authors.lastname: Yaacob
authors.affiliation: Regenerative Medicine Cluster, Universiti Sains Malaysia, Advanced Medical & Dental Institute, No. 1-8, Persiaran Seksyen 4/1, Bandar Putra Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia. Electronic address: rahim@amdi.usm.edu.my.
authors.forename: Abdul Rahim
authors.initials: AR
authors.lastname: Hussein
authors.affiliation: Hemophilia Clinic, National Blood Centre, Jalan Tun Razak, 50400, Wilayah Persekutuan, Kuala Lumpur, Malaysia. Electronic address: faraizah@gmail.com.
authors.forename: Faraizah
authors.initials: F
authors.lastname: Abdul Karim
authors.affiliation: Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia. Electronic address: ahazri@sirim.my.
authors.forename: Ahmad Hazri
authors.initials: AH
authors.lastname: Abdul Rashid
authors.affiliation: Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia. Electronic address: zanariah@sirim.my.
authors.forename: Zanariah
authors.initials: Z
authors.lastname: Ujang
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004343:Drug Implants; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood* / Q000188:drug therapy*
chemical_list: D004343:Drug Implants; D006490:Hemostatics; D009844:Oligosaccharides; C514968:carboxymethyl-chitosan; C493484:oligochitosan; D002686:Chitin; D048271:Chitosan
keywords: Hemostasis; N,O-Carboxymethylchitosan (NO-CMC); Oligo-Chitosan (O-C); Platelet mechanisms; Von Willebrand disease (vWD)