Objective: To study the influence of virus photoinactivation with methylene blue (MB) on the coagulation factors of fresh frozen plasma (FFP) and the corresponding cryoprecipitates and cryosupernatants derived from it. Materials and Methods: The photoinactivation procedure of the German Red Cross (Springe) was applied using Biomat (Grifols, Spain). Twenty isogroup pools of three plasma units were made from 60 U of FFP. The pools were split into three bags. One of them was photoinactivated, and pre- and postinactivation samples (MB-plasma) were obtained. The second bag was treated in the same way, followed by the preparation of MB-cryoprecipitate and MB-cryosupernatant. The third bag was not photoinactivated, and was processed in the same way to obtain control cryoprecipitate and cryosupernatant. The prothrombin time and activated partial thromboplastin time were analysed, as well as fibrinogen, factors (F) II, V, VII, VIII, IX, XI and XIII, antithrombin III, von Willebrand (vW) F:RCo, vWF:Ag and the multimeric structure of vWF. Results: In plasma, the proteins most sensitive to photoinactivation were fibrinogen, FV, FVIII, FIX and FXI (24, 32, 28, 23 and 27% loss, respectively). In the MB-cryoprecipitate, the losses were higher for FVIII (23%), moderate for fibrinogen, FXIII and vWF:RCo (18, 14 and 13%, respectively) and minimal (only 3%) for vWF:Ag. In MB-cryosupernatants, the losses were higher for FV (26%) and moderate for fibrinogen (16%), FIX (18%) and FXI (19%), as well as for FII and FXIII (15%). The multimeric structure of vWF was not modified in MB-plasma or in MB-cryoprecipitates. The supernatants (both MB treated as well as controls) showed an absence of multimers of very high and high molecular weight. Conclusions: The quantitative and qualitative conservation of coagulation factors achieved in MB-plasma-derived products suggest that they are useful for the global replacement of coagulation factors and for deficiencies in FV and FXI. In countries lacking the economic resources to obtain virally inactivated concentrates, MB-cryoprecipitates could be useful in von Willebrand’s disease and fibrinogen and FXIII deficiencies. MB-cryosupernatants could be employed in thrombotic thrombocytopenic purpura, in the correction of total or partial deficiencies of prothrombin complex factors and in specific deficiencies of FV and FXI.

1.
Burnouf T: Attenuation of viruses in therapeutic plasma. Sangre (Barc) 1994;39(suppl 1):179–182.
2.
Horowitz B, Bonomo R, Prince AM, Chin SN, Brotman B, Shulman RW: Solvent/detergent-treated plasma: A virus-inactivated substitute for fresh frozen plasma. Blood 1992;79:826–831.
3.
Lambrecht B, Mohr H, Knüver-Hopf J, Schmitt H: Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light. Vox Sang 1991;60:207–213.
4.
Mohr H, Lambrecht B, Selz A: Photodynamic virus inactivation of blood components. Immunol Invest 1995;24:73–85.
5.
Lambrecht B, Norley SG, Kurth R, Mohr H: Rapid inactivation of HIV-1 in single donor preparations of human fresh frozen plasma by methylene blue/light treatment. Biologicals 1994;22:227–231.
6.
Zeiler T, Riess H, Wittman G, et al: The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma. Transfusion 1994;34:685–689.
7.
Aznar JA, De Miguel A, Franco E, Hernández JM, Tascón A, Vesga MA: Indicaciones terapéuticas del plasma fresco fotoinactivado con azul de metileno. Rev Iberoamer Tromb Hemostasia 1998;11:60–62.
8.
Aznar JA, Molina R, Montoro JM: Factor VIII/von Willebrand factor molecular complex in methylene blue-treated fresh plasma. Transfusion 1999;39:748–751.
9.
Indicaciones clínicas y riesgos del plasma fresco congelado. Subdirección General de Planification Sanitaria. Ministerio de Sanidad y Consumo (Conferencia de Consenso). Med Clin (Barc) 1994;102:225–227.
10.
Mohr H, Knüver-Hopf J, Lambrecht B, Scheidecker H, Schmitt H: No evidence for neoantigens in human plasma after photochemical virus inactivation. Ann Hematol 1992;65:224–228.
11.
Knüver-Hopf J, Lambrecht B, Mohr H: An electrophoretic study and amino acid analysis of blood proteins before and after photodynamic treatment of human plasma. Infusionsther Transfusionsmed 1995;22(suppl 1):5–7.
12.
Tissot JD, Hochstrasser DF, Schneider B, Morgenthaler JJ, Schneider P: No evidence for protein modifications in fresh frozen plasma after photochemical treatment: An analysis by high-resolution two-dimensional electrophoresis. Br J Haematol 1994;86:143–146.
13.
Schneppenheim R, Plendl H, Budde U: Luminography – an alternative assay for detection of von Willebrand factor multimers. Tromb Haemost 1988;60:133–136.
14.
Selz A, Lambrecht B, Herms O, Marks F, Mohr H: Influence of methylene blue/light treatment on the activity of coagulation factors in human plasma. ISBT V Congress, Venice, 1995.
15.
Pohl U, Mohr H: Experiences in the clinical use of plasma photodynamically virus inactivated by methylene blue/light procedure. 24th ISBT Congress. Makuhari Messe, Japan, 1996, poster 1/2E-41 OP.
16.
Pohl U, Becker M, Papstein C, et al: Methylene blue virus inactivated fresh frozen plasma (MB-VIP) in the treatment of patients with thrombotic thrombocytopenic purpura (TTP). ISTB V Regional (IV European) Congress, Venice, 1995, poster 213.
17.
Bolton-Maggs PHB: The management of factor XI deficiency. Haemophilia 1998;4:683–688.
18.
Tsai HM, Lian EC: Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998;339:1585–1594.
19.
Furlan M, Robles R, Galbusera M, et al: von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Eng J Med 1998;339:1578–1584.
20.
Freeman JW, Williamson LM, Llewelyn C, Fisher N, Allain JP, Bellamy M, et al: A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during orthotopic liver transplantation. Vox Sang 1998;74(suppl 1):225–229.
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