Methylene Blue-treated Plasma Research Articles

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data

IntroductionTherapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial.Patients and methods: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. ResultsDuring the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). ConclusionMBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

Anaphylactic reaction after methylene blue-treated plasma transfusion

Methylene blue-treated fresh-frozen plasma (MB-FFP) is mainly used in Europe. The advantage of the methylene blue system is that units can be treated individually. The combined action of methylene blue and illumination is a photodynamic process preventing viral RNA and DNA replication. We report the first immediate allergic hypersensitivity reaction to methylene blue-treated plasma transfusion. The clinical course and subsequent assessment of the allergic reaction, including skin tests and basophil activation test, confirmed methylene blue-induced IgE-mediated anaphylaxis. All immediate reactions after MB-FFP transfusion should be investigated to document the underlying mechanism.

Characteristics of prion‐filtered red cells suspended in pathogen‐inactivated plasma (MB treated or solvent‐detergent treated) for neonatal exchange transfusion

Neonates undergoing exchange transfusion require <5-day-old red cells suspended in plasma. This study assesses the effect of replacing the saline, adenine, glucose and mannitol (SAGM) of prion reduced (P-Capt) red cells with either methylene blue-treated plasma (MBTFFP) or OctaplasLG to reduce the risk of variant Creutzfelt-Jakob disease transmission. Twenty leucoreduced red cell units in SAGM were prion reduced on day 1. The SAGM was replaced by MBTFFP (n=10) or OctaplasLG (n=10). The units were irradiated and stored at 4°C for 24 h. A further 20 units were stored for 5 days before being processed as above. Haemolysis (%), potassium, ATP, 2,3-DPG and plasma proteins were measured. Haemolysis remained low (≤0·16%). Following irradiation and storage, red cells in both types of plasma showed similar changes in potassium and ATP concentrations. The 2,3-DPG concentrations were well maintained although lower in red cells in OctaplasLG compared with those in MBTFFP (4·79 vs. 6·83 μmoles/g Hb on day 6). MBTFFP contained lower concentrations of fibrinogen, FV and FVIII. In OctaplasLG, alpha-2-antiplasmin was approximately 0·4 U/ml lower than in MBTFFP. After 24 h at 4°C, free protein S in OctaplasLG fell from 0·82 to 0·57 IU/ml. Other plasma proteins, in both types of plasma, were stable. Red cells in both types of plasma demonstrated similar storage characteristics. The plasma proteins, except protein S in OctaplasLG, were stable over 24 h at 4°C in both types of plasma, and low FVIII concentrations were noted in the MBTFFP (group O) units used.

Thrombin Generation Capacity of Methylene Blue-Treated Plasma Prepared by the Theraflex MB Plasma System

Background: Methylene blue (MB) / light treatment is a well-known procedure for the inactivation of pathogens in fresh frozen plasma (FFP). Aim of the current study was to investigate the thrombin generation (TG) characteristics and quality of MB plasma prepared by the Theraflex MB Plasma System. Methods: Single donor plasma units (n = 18) were MB/light-treated, with sampling before and after processing. Preparation included leukocyte depletion, addition of MB pill prior to illumination, and depletion of MB and photoproducts by filtration. Different plasma parameters and TG were measured. TG additionally was determined in solvent/detergent plasma (n = 8). Results: MB/light treatment significantly affected factors V, VIII and XI, which were decreased by 9–18%. While the antigen level was not affected, fibrinogen according to Clauss was decreased by 7%, correlating with a 12% prolongation of TT and RT. The total amount of free thrombin generated, given as ‘area under the curve’ (AUC), was comparable for untreated (93 ± 18% of normal plasma) and MB/light-treated plasma (95 ± 20%). Also peak thrombin concentration was not significantly affected by treatment (94 ± 11% (untreated) vs. 96 ± 12% (treated)). The ‘time to peak’ value (TTP) was 105% of normal plasma for untreated FFP and 89% for MB-treated plasma. Conclusion: For plasma treated with the Theraflex MB Plasma System no profound influence of MB/ light treatment on the characteristics of thrombin generation was detected. In concordance with data from the literature, coagulation factors V, VIII and XI were decreased due to MB/ light treatment. Decrease was less than 20%.

Therapeutic plasma exchange and plasma infusion in thrombotic microvascular syndromes

Plasma exchange (PE) is the most important treatment in thrombotic microangiopathies (TMAs) mainly encompassing thrombotic thrombocytopenic purpura (TTP) and adult hemolytic syndrome (HUS). This therapeutic measure has substantially improved clinical outcome. One plasma volume corresponding to 40 ml/kg of body weight is exchanged daily until the platelet count is above 150×10 9/l or 100×10 9/l and continues to rise or remains constantly after cessation of treatment. Exacerbations and late recurrences demand reapplication of daily PE. Twice daily PEs are initiated if the response to initial treatment is poor. The importance of additional or alternate measures including glucocorticoids, antiplatelet agents, splenectomy, intravenous immunoglobulins, protein A columns, vincristine, cyclosporine, and cyclophosphamide is uncertain. Whether cryosupernatant plasma (CSP) or solvent/detergent-treated (SDP) plasma is superior to standard fresh frozen plasma (FFP) remains to be determined. Methylene blue-treated plasma (MBP) seems to be less effective than standard FFP.

Role of methylene blue-treated or fresh-frozen plasma in the response to plasma exchange in patients with thrombotic thrombocytopenic purpura.

Twenty patients with thrombotic thrombocytopenic purpura (TTP) underwent plasma exchange using either standard fresh-frozen plasma (Group A, n = 13) or methylene blue-treated plasma (Group B, n = 7). Both groups presented similar characteristics except that bilirubin values were higher in Group A (P < 0.05). The complete remission rate was higher in Group A than B (69% versus 57%). The mean number of procedures was higher in Group B (21 +/- 7 versus 11 +/- 3, P < 0.01) and the mean duration of hospitalization was also longer (37 +/- 12 d versus 22 +/- 11 d; P < 0.01). Our study shows that the use of methylene blue-treated fresh-frozen plasma to treat TTP is associated with a higher number of plasma exchanges and greater transfusion requirements without improving clinical results.

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

The effect of virus inactivation of fresh plasma with methylene blue has been studied on the factor VIII/von Willebrand factor molecular complex (FVIII/vWF), factor XIII, and fibrinogen. FVIII function or activity, vWF activity, vWF antigen, vWF:Ag, vWF multimeric structure, fibrinogen, and factor XIII were analyzed in paired samples of control fresh plasma (untreated) and the same fresh plasma treated with methylene blue. Treated plasma was filtered (0.8-1.2 microm), mixed with a methylene blue solution (300 microg/L), and illuminated at 50,000 lux for 30 minutes on both sides. Average loss of biologic activity of coagulation factors studied was 25 percent (FVIII function, 29%; fibrinogen, 39%; factor XIII, 16%; and vWF activity, 18%). Reduction in vWF activity was significantly lower than that in FVIII function (p<0.05), and the vWF multimeric structure did not show alterations. 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.