Factor VIII/von Willebrand factor complex in methylene blue‐treated fresh plasma

Aznar, José A.; Molina, R; Montoro, Juan

doi:10.1046/j.1537-2995.1999.39070748.x

Cited by 38 publications

(36 citation statements)

References 10 publications

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“…Our results are slightly different to those described by the German Red Cross Blood Transfusion Service for FFP [14], reporting a reduction of 20% for FV. The reduction in FVIII is similar to that found in previous studies conducted by our group [7, 8]using another method for the application of photoinactivation with MB (Baxter system), which freezes and thaws the plasma only once.…”

Section: Discussionsupporting

confidence: 88%

“…One possible strategy for increasing the content of FVIII/vWF in MB-plasma would be the exclusive use of plasma from blood groups other than O, since they present ostensibly higher rates of these factors [8], as is shown in table 2.…”

Section: Discussionmentioning

confidence: 99%

“…MB treatment involves some loss of several biological activities found in the product. Nevertheless, the recovery of coagulation factors in MB-treated plasma is sufficient for it to be used as a therapeutic product [3, 4, 5, 7, 8], at least for the indications admitted nowadays for fresh frozen plasma (FFP) [9]. No evidence suggests that MB treatment generates structural modifications of plasma proteins that might lead to the production of neoantigens [10, 11, 12]or cause a greater number of allergic reactions or toxicity in recipients.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Methylene Blue Photoinactivation Treatment on Coagulation Factors from Fresh Frozen Plasma, Cryoprecipitates and Cryosupernatants

Aznar¹,

Bonanad²,

Montoro³

et al. 2000

Vox Sanguinis

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Influence of Methylene Blue Photoinactivation Treatment on Coagulation Factors from Fresh Frozen Plasma, Cryoprecipitates and Cryosupernatants

Aznar¹,

Bonanad²,

Montoro³

et al. 2000

Vox Sanguinis

Self Cite

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“…We found considerable differences in hemostatic quality between the three plasma types that certainly are due to differences in the preparation and inactivation process. The data are in line with other reports [11][12][13][14][15][16][17][18][19][20][21] and need not to be discussed further. However, none of these differences was related to the thawing procedure.…”

Section: Discussionsupporting

confidence: 91%

Thawing of Fresh Frozen Plasma and Virus-Inactivated Plasma – Suitability of Microwave Oven

Beck¹,

Schüftan²,

Schubert³

et al. 2002

Transfus Med Hemother

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Background: Microwaves basically are a quick alternative to water bath and water bag system (WB) for thawing of fresh frozen plasma (FFP) for transfusion. Already in the 1980s we developed, together with a manufacturer (Infusotherm, Zeipel, Göttingen, Germany), a microwave oven (MWO) which allowed thawing of FFP much faster and more gentle than with WB. With the addition of e.g. methylene blue or solvents and detergents to plasma for virus inactivation, the question arises if microwaves might have a negative impact on virus-inactivated plasma (VIP) by enhancing activation processes or impairment of proteins which have been initiated by the inactivation procedure, resulting in reduced hemostatic activity. Material and Methods: 30 solvent/detergent-inactivated plasma (SDP), 25 methylene blue-inactivated plasma (MBP), and 30 conventionally produced FFP units were investigated immediately and 2 h after thawing by MWO and a modified WB system for the following coagulation parameters: All plasma clotting factors and the corresponding complex coagulation tests, prothrombin fragment F1+2, d-dimers, thrombin-antithrombin, plasmin-antiplasmin, fibrinogen degradation products, reptilase and thrombin time, antithrombin, protein C, protein S, α2-antiplasmin, von Willebrand factor antigen, Ristocetin cofactor, and von Willebrand factor multimers. The effect on primary hemostasis was investigated by means of in vitro bleeding test (IVBT; Thrombostat 4000, VDG, Seeon, Germany) by addition of plasma to fresh blood of healthy donors. Results: Reaching comparable end temperature (MWO: SDP 31.4 °C, MBP 31.6 °C, FFP 31.7 °C; WB: SDP 32.2 °C, MBP 31.8 °C, FFP 31.5 °C), thawing with MWO (SDP 16.3 min, MBP 19.7 min, FFP 19.5 min) was considerably shorter than with WB (SDP 31.2 min, MBP 31.8 min, FFP 32 min). Under these conditions no significant differences of the hemostatic parameters which could be attributed to the thawing method were found. Only the known differences between the different plasma types which are due to production and inactivation process have been proven. Conclusion: The used MWO is suitable for thawing of FFP as well as VIP. In regard to the significant shorter thawing time, it has clear advantages, particularly in massive transfusion.

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“…Similarly, in numerous reports the photoinactivation of plasma with methylene blue (methylene blue-FFP) resulted in a 20-40% decrease of fibrinogen function [18,19,34,35]. Methylene blue at the concentration of 1 mmol/l and 1 h exposure to white fluorescent light at 45 000 lux is routinely applied [36] but under these conditions only Data presented as the mean AE SD derived from four independent experiments.…”

Section: Discussionmentioning

confidence: 95%

Haemostatic properties of human plasma subjected to a sterilizing dose of gamma irradiation in the presence of ascorbate

Żbikowska

Nowak²,

Wachowicz³

2007

Blood Coagulation &Amp; Fibrinolysis

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The objective was to study the effects of gamma irradiation, in the presence of sodium ascorbate, on coagulation/fibrinolytic activity of fresh frozen plasma to be applied to inactivate the transfusion-transmitted viruses in plasma-derived products. Plasma was irradiated (50 kGy total dose, on dry ice) using a 60Co source. The plasma proteins were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blot and the following parameters estimated: prothrombin time, functional fibrinogen concentration, thrombin-induced fibrinogen polymerization, plasminogen activity, and tissue-type plasminogen activator-induced conversion of plasminogen to plasmin. In irradiated plasma a moderate fragmentation of the most labile plasma proteins was found. The prothrombin time was prolonged (1.5-fold), functional fibrinogen was significantly reduced (60%), fibrinogen polymerization was impaired, plasminogen was predominantly maintained (90%) and tissue-type plasminogen activator-induced conversion of plasminogen to plasmin was unchanged. Ascorbate (25 mmol/l) raised the level of functional fibrinogen in irradiated plasma (to 50%; P=0.0245) and slightly accelerated its polymerization. The small protective effect of ascorbate might be due to inhibition of the radiation-induced fibrinogen oxidation and/or fragmentation but addition of other antioxidants/stabilizers would be crucial when a high irradiation dose, an effective treatment for inactivation of the most resistant viruses, is applied.

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Factor VIII/von Willebrand factor complex in methylene blue‐treated fresh plasma

Abstract: Methylene blue-treated plasma and the cryoprecipitates obtained from it may be effective for replacement therapy in cases of von Willebrand disease and deficiencies of factor XIII and fibrinogen, but the clinical studies are needed to verify that possibility.

Cited by 38 publications

References 10 publications

Influence of Methylene Blue Photoinactivation Treatment on Coagulation Factors from Fresh Frozen Plasma, Cryoprecipitates and Cryosupernatants

Influence of Methylene Blue Photoinactivation Treatment on Coagulation Factors from Fresh Frozen Plasma, Cryoprecipitates and Cryosupernatants

Thawing of Fresh Frozen Plasma and Virus-Inactivated Plasma – Suitability of Microwave Oven

Haemostatic properties of human plasma subjected to a sterilizing dose of gamma irradiation in the presence of ascorbate

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