Selective factor VIII and V inactivation by iminodiacetate ion exchange resin through metal ion adsorption.
The procoagulant activity of factors VIII and V depends on the presence of metal ion(s). We examined the effect of cation-exchange resins with different functional groups on both factors, of which only reaction with iminodiacetate resin resulted in the complete loss of their activity levels in plasma. However, the antigen level of factor VIII was preserved by >95%. This resin reduced divalent cations content present in factor VIII preparations, indicating that it inactivated this factor by direct deprivation of predominant Ca(2+) (>Mn(2+)>>Cu(2+)), rather than adsorption of the factor itself. The antigen level of recombinant factor VIII alone was decreased by >95% by reaction with resin, whilst that complexed with von Willebrand factor was preserved by >95%. Iminodiacetate resin-treated plasma was evaluated by measuring factor VIII and V activity in plasma with various levels of either activity. These were significantly correlated to the values obtained using factor VIII- or V-deficient plasma prepared commercially by immunodepletion. We demonstrated that iminodiacetate resin-induced factors VIII and V inactivation is because of direct deprivation of metal ions, predominantly Ca(2+), which is more essential for the functional structure of their molecules. Furthermore, iminodiacetate resin-treated plasma would be useful as a substrate for measuring the activity of these factors.
Takeyama
Masahiro
M
Department of Paediatrics, Nara Medical University, Kashihara, Nara, Japan.
Nogami
Keiji
K
Okuda
Masahiro
M
Sakurai
Yoshihiko
Y
Matsumoto
Tomoko
T
Tanaka
Ichiro
I
Yoshioka
Akira
A
Shima
Midori
M
D001780:Blood Coagulation Tests / Q000379:methods; D002118:Calcium / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D005165:Factor V / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D005169:Factor VIII / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007098:Imino Acids / Q000737:chemistry; D007163:Immunosorbent Techniques; D007475:Ion Exchange Resins; D008345:Manganese / Q000737:chemistry
D007098:Imino Acids; D007475:Ion Exchange Resins; D008345:Manganese; D003300:Copper; C078147:F8 protein, human; D005165:Factor V; D005169:Factor VIII; D002118:Calcium; C008109:iminodiacetic acid