Flebogamma(®) DIF (intravenous immunoglobulin) purification process effectively eliminates procoagulant activities.
BACKGROUND
Studies have demonstrated that traces of activated factor XI (FXIa) present in specific brands of intravenous immunoglobulin (IVIG) concentrates may pose a thrombogenic risk.


OBJECTIVE
To characterize procoagulant activity during fractionation and the elimination capacity of the Flebogamma(®) DIF (Grifols' IVIG) manufacturing process.


METHODS
Flebogamma(®) DIF fractionation steps included cryoprecipitate supernatant (Cryo/S), Fraction (Fr) I supernatant, and Fr II + III suspension. Purification steps included ultrafiltrate I, acid treatment, and pasteurization. Samples were assessed for total protein, IgG, and procoagulant activation markers.


RESULTS
Cryo/S showed no procoagulant activity for prekallikrein activator (PKA), kallikrein-like, and non-activated partial thromboplastin time (NaPTT) with normal (-PPP) or FXI-deficient (-FXI) platelet poor plasma. Thrombin generation test (TGT)-PPP and TGT-FXI were <83-148 and <53-197 nM thrombin, respectively. Shortened NaPTTs (100-296 s), high PKA (51-119 IU/mL), kallikrein-like activities (0.043-0.075 ΔAU/min), positive TGTs (98-298 nM), and FXIa (9.5-14.0 ng/mL) were detected in Fr II + III. After pasteurization, no residual evidence of any procoagulant activity marker was observed, including the final IVIG concentrate at 5% or 10% protein. Results were similar in Fr II + III from different IVIG manufacturing facilities.


CONCLUSIONS
The Flebogamma(®) DIF production process is capable of eliminating procoagulant activity because of its purification steps.
Instituto Grifols S.A., Research and Development Area, Polígon Llevant, Can Guasch, 2, 08150 Parets del Vallès, Barcelona, Spain. Electronic address: marta.jose@grifols.com.
Marta
M
José
Núria
N
Marzo
Berta
B
Pons
Aida
A
Herrerias
Laura
L
López
Merche
M
Faro
Maite
M
López
Juan I
JI
Jorquera
D005591:Chemical Fractionation / Q000379:methods; D003029:Coagulants / Q000032:analysis / Q000302:isolation & purification*; D004340:Drug Contamination / Q000517:prevention & control*; D015945:Factor XIa / Q000032:analysis / Q000302:isolation & purification*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000032:analysis / Q000302:isolation & purification* / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results
D003029:Coagulants; D016756:Immunoglobulins, Intravenous; D015945:Factor XIa
Activated coagulation factor XI; Flebogamma(®) DIF; Intravenous immunoglobulin; Procoagulant activity; Purification process; Thrombotic risk