Proteomic characterization of plasma-derived clotting factor VIII-von Willebrand factor concentrates.
Proteomic methods were used to identify the levels of impurities in three commercial plasma-derived clotting factor VIII-von Willebrand factor (FVIII/VWF) concentrates. In all three concentrates, significant amounts of other plasma proteins were found. In Octanate and Haemoctin, two concentrates developed in the 1990s, the major impurities identified were inter-alpha inhibitor proteins, fibrinogen and fibronectin. These two concentrates were also found to contain additional components such as clotting factor II (prothrombin) that are known activators of FVIII. In Wilate, a recently developed FVIII/VWF concentrate, the amount of these impurities was significantly reduced. Batch-to-batch variations and differences between three investigated products were detected using iTRAQ, an isotope labeling technique for comparative MS, demonstrating the potential value of this technique for quality control analysis. The importance of thorough proteomic investigations of therapeutic FVIII/VWF preparations from human plasma is also discussed.
Clifton
James G
JG
Proteomics Core, COBRE Center for Cancer Research Development, Rhode Island Hospital, Providence, RI, USA.
Huang
Feilei
F
Kovac
Spomenka
S
Yang
Xinli
X
Hixson
Douglas C
DC
Josic
Djuro
D
D001777:Blood Coagulation; D002845:Chromatography; D005169:Factor VIII / Q000032:analysis* / Q000592:standards; D005340:Fibrinogen / Q000032:analysis; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014841:von Willebrand Factor / Q000032:analysis* / Q000592:standards
D005353:Fibronectins; D014841:von Willebrand Factor; D005169:Factor VIII; D005340:Fibrinogen