New plasma protein C and protein S concentrate: A synergy for therapeutic purposes.
Vox Sang
; 119(3): 193-202, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38018260
ABSTRACT
BACKGROUND AND OBJECTIVES:
Deficiencies of protein C (PC) or protein S (PS) are rare diseases, characterized by mutations in the PC or PS genes, which encode plasma serine proteases with anti-coagulant activity. Severe PC or PS deficiencies manifest in early life as neonatal purpura fulminans, a life-threatening heamorrhagic condition requiring immediate treatment. First-line treatment involves replacement therapy, followed by maintenance with anti-coagulants. Replacement therapy with specific protein concentrates is currently only limited to PC, and therefore, a PC + PS concentrate represents a useful addition to therapeutic options, particularly for severe PS deficiency. Further, the production of a PC + PS concentrate from unused plasma fractionation intermediates would impact favourably on manufacturing costs, and consequently therapy prices for patients and health systems. MATERIALS ANDMETHODS:
Several chromatographic runs were performed on the same unused plasma fractionation intermediates using different supports to obtain a PC/PS concentrate. The best chromatographic mediums were chosen, in terms of specific activity and recovery. A full process of purification including virus inactivation/removal and lyophilization steps was set up.RESULTS:
The final freeze-dried product had a mean PC concentration of 47.75 IU/mL with 11% of PS, and a mean specific activity of 202.5 IU/mg protein, corresponding to over 12,000-fold purification from plasma.CONCLUSION:
The development of a novel concentrated PC/PS mixture obtained from a waste fraction of other commercial products could be used for its potential therapeutic role in the management of neonatal purpura fulminans pathology.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein C Deficiency
/
Purpura Fulminans
Limits:
Humans
/
Newborn
Language:
En
Journal:
Vox Sang
Year:
2024
Document type:
Article
Affiliation country:
Italy