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Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial
Brixner V, Bug G, Pohler P, Krämer D, Metzner B, Voß A, Casper J, Ritter U, Klein S, Alakel N, et al
Haematologica. 2021
Abstract
Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).
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2.
Hemostatic efficacy of pathogen-inactivated- versus untreated- platelets: a randomized controlled trial
van der Meer P F, Ypma P F, van Geloven N, van Hilten J A, van Wordragen-Vlaswinkel R J, Eissen O, Zwaginga J J, Trus M, Beckers E A M, Te Boekhorst P, et al
Blood. 2018;132((2):):223-231
Abstract
Pathogen inactivation of platelet concentrates reduces the risk of blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen inactivated platelets using riboflavin and ultraviolet B illumination technology (intervention) compared to standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion treatment periods in which the patient had grade 2 or higher bleeding as defined by World Health Organization (WHO) criteria. Between November 2010 and April 2016, 469 unique patients were randomized to 567 transfusion treatment periods (283 in the control arm, 284 in the intervention arm). There was a 3% absolute difference in grade ≥ 2 bleeding in the intention-to-treat analysis: 51% of the transfusion treatment periods in the control arm and 54% in the intervention arm (95% CI -6 to 11, p-value for noninferiority 0.012). In the per-protocol analysis, however, difference in grade ≥ 2 bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI -2 to 18, p-value for noninferiority 0.19). Transfusion increment parameters were about 50% lower in the intervention arm. There was no difference in the proportion of patients developing HLA class I alloantibodies. In conclusion, the noninferiority criterion for pathogen inactivated platelets was met in the intention-to-treat analysis. This finding was not demonstrated in the per protocol analysis. (The Netherlands National Trial Registry number: NTR2106).
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3.
Coagulation Factor Activities Changes Over 5 Days in Thawed Fresh Frozen Plasma Stored at Different Initial Storage Temperatures
Noordin SS, Karim FA, Mohammad WMZBW, Hussein AR
Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion. 2018;34((3)):510-516.
Abstract
Thawed plasma is fresh frozen plasma (FFP) that has been stored for 5 days at 1-6 degrees C. Duration of storage and different storage temperatures might affect the coagulation factor activity in thawed FFP. This study measured the changes of coagulation factor activities over 5 days in thawed FFP and stored at two different initial storage temperatures. Thirty-six units of FFP, which consisted of nine units each from blood groups A, B, AB, and O, were thawed at 37 degrees C. Each unit was divided into two separate groups (Group A and Group B) based on initial storage temperature. The first group was stored at 2-6 degrees C for 5 days (Group A). The second group was stored at 20-24 degrees C for initial 6 h followed by 2-6 degrees C for 5 days (Group B). Prothrombin time (PT), activated partial thromboplastin time (APTT), coagulation factor activities of fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, and von Willebrand factor antigen (vWF Ag) were assessed at baseline after thawing, at 6 h, and on days 1, 3, and 5 of storage for both groups. All coagulation factors mean activities in both storage groups decreased significantly over 5 days of storage. The mean FVIII activity at day 5 of storage was 36.9% in Group A and 39.8% in Group B. The other coagulation factors mean activities were > 50% on day 5 of storage in both groups. The coagulation factor activities of thawed FFP stored for 5 consecutive days were reduced in the two storage groups but most of the activities were still above 30%. This study suggests that thawed FFP stored for 5 days has the potential to ameliorate coagulation factor deficiencies in affected patients.
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4.
A multi-centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion
Lozano M, Knutson F, Tardivel R, Cid J, Maymo RM, Lof H, Roddie H, Pelly J, Docherty A, Sherman C, et al
British Journal of Haematology. 2011;153((3):):393-401.
Abstract
Bacteria in platelet components (PC) may result in transfusion-related sepsis (TRS). Pathogen inactivation of PC with amotosalen (A-PC) can abrogate the risk of TRS and hence facilitate storage to 7 d. A randomized, controlled, double-blinded trial to evaluate the efficacy and safety of A-PC stored for 6-7 d was conducted. Patients were randomized to receive one transfusion of conventional PC (C-PC) or A-PC stored for 6-7 d. The primary endpoint was the 1 h corrected count increment (CCI) with an acceptable inferiority of 30%. Secondary endpoints included 1- and 24-h count increment (CI), 24-h CCI, time to next PC transfusion, red blood cell (RBC) use, bleeding and adverse events. 101 and 100 patients received A-PC or C-PC respectively. The ratio of 1-h CCI (A-PC:C-PC) was 0·87 (95% confidence interval: 0·73, 1·03) demonstrating non-inferiority (P = 0·007), with respective mean 1-h CCIs of 8163 and 9383; mean 1-h CI was not significantly different. Post-transfusion bleeding and RBC use were not significantly different (P = 0·44, P = 0·82 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2·2 vs. 2·3 d, P = 0·72). Storage of A-PCs for 6-7 d had no impact on platelet efficacy.
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5.
Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction
Kerkhoffs JL, van Putten WL, Novotny VM, Te Boekhorst PA, Schipperus MR, Zwaginga JJ, van Pampus LC, de Greef GE, Luten M, Huijgens PC, et al
British Journal of Haematology. 2010;150((2):):209-17.
Abstract
Pathogen reduction (PR) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness. We conducted a multicentre, open-label, randomized, non-inferiority trial comparing the clinical effectiveness of buffy-coat derived leukoreduced platelet concentrates (PC) stored for up to 7 d in plasma with platelets stored in platelet additive solution III (PASIII) without and with treatment with amotosalen-HCl/ultraviolet-A (UVA) photochemical pathogen reduction (PR-PASIII). Primary endpoint of the study was 1-h corrected count increment (CCI). Secondary endpoints were 24-h CCI, bleeding, transfusion requirement of red cells and PC, platelet transfusion interval and adverse transfusion reactions. Compared to plasma-PC, in the intention to treat analysis of 278 evaluable patients the mean difference for the 1-h CCI of PR-PASIII-PC and PASIII-PC was -31% (P < 0. 0001) and -9% (P = n. s. ), respectively. Twenty-seven patients (32%) had bleeding events in the PR-PASIII arm, as compared to 19 (19%) in the plasma arm and 14 (15%) in the PASIII arm (P = 0. 034). Despite the potential advantages of pathogen (and leucocyte) inactivation of amotosalen-HCl/UVA-treated platelet products, their clinical efficacy is inferior to platelets stored in plasma, warranting a critical reappraisal of employing this technique for clinical use.
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6.
A multicenter randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma
Kerkhoffs JL, Eikenboom JC, Schipperus MS, van Wordragen-Vlaswinkel RJ, Brand R, Harvey MS, de Vries RR, Barge R, van Rhenen DJ, Brand A
Blood. 2006;108((9):):3210-5.
Abstract
Randomized studies testing the clinical efficacy of platelet additive solutions (PASs) for storage of platelets are scarce and often biased by patient selection. We conducted a multicenter, randomized study to investigate clinical efficacy of platelets stored in PAS II versus plasma, also including patients with clinical complications associated with increased platelet consumption. A total of 168 evaluable patients received pooled buffy coat-derived platelet concentrates (PCs) suspended in either plasma (n = 354) or PAS II (n = 411) stored up to 5 days. Both univariate as well as multivariate analysis showed a significant effect of used storage medium in regard to 1- and 24-hour count increments and corrected count increments, in favor of plasma PCs. However, there were no significant differences between the groups regarding bleeding complications and transfusion interval. Adverse transfusion reactions occurred significantly less after transfusions with PAS II PCs (P = . 04). Multivariate analysis showed no significant effect of the used storage medium on the incidence of 1- and 24-hour transfusion failure. We showed safety and efficacy of PAS II PCs in intensively treated patients; however, plasma PCs show superior increments.
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7.
Effects of storage time on quantitative and qualitative platelet function after transfusion
Rosenfeld BA, Herfel B, Faraday N, Fuller A, Braine H
Anesthesiology. 1995;83((6):):1167-72.
Abstract
BACKGROUND Platelet transfusions are being used increasingly in patients with thrombocytopenia to improve hemostatic function before surgery and invasive procedures. However, there are limited data on the immediate quantitative and qualitative platelet response after transfusion. Some authors have suggested that transfused platelets require time in vivo to regain maximal function, which is dependent on the duration of platelet storage. Therefore, the timing of surgery and invasive procedures with optimal platelet function may not be occurring. METHODS Twenty-five patients with thrombocytopenia from ablation chemotherapy and total body irradiation (before bone marrow transplantation), were randomized to receive either 1-day (fresh) or 4-day stored platelets. No patient had infection, organ system dysfunction, or previous platelet transfusion. Single-donor platelets were transfused (1 unit/10 kg body weight) over 60 min. Whole blood from an indwelling central venous catheter was obtained before, immediately after, and 1, 2, and 24 h after transfusion. Platelet number was measured on a Coulter counter and platelet reactivity was measured on a Coulter counter and platelet reactivity was measured using agonist-induced whole blood impedance aggregometry (ohms) and dense granule release (adenosine triphosphate [ATP]). RESULTS Platelet number increased similarly (21,000 +/- 2,000/mm3 to 76,000 +/- 7,000/MM3 AND 20,000 +/- 1,000/MM3 TO 65,000 +/- 4,000/MM3) after transfusion in the 1- and 4-day stored platelets, respectively. These levels were maintained for 2 h after transfusion in both groups and then decreased similarly (26% and 27%) at 24 h. Agonist-induced platelet aggregation increased immediately after transfusion to 5 micrograms/ml collagen (0.7 +/- 0.4 to 11.4 +/- 1.0 ohms and 0.1 +/- 0.1 to 5.2 +/- 1.0 ohms), 10 micrograms/ml collagen, (1.5 +/- 0.7 to 18.0 +/- 1.9 ohms and 0.6 +/- 0.4 to 10.0 +/- 1.6 ohms) and ristocetin (0.7 +/- 0.4 to 10.1 +/- 1.7 and 0.1 +/- 0.7 to 6.2 +/- 1.0 ohms), in 1- and 4-day, stored platelets, respectively and persisted unchanged in both groups for 2 h. Fresh platelets were hyperaggregable compared to 4-day stored platelets for collagen-induced (5 micrograms/ml and 10 micrograms/ml) aggregation. Agonist-induced platelet dense granule release (ATP) increased immediately after transfusion to 5 micrograms/ml collagen (42 +/- 18 to 410 +/- 49 picomoles ATP and 20 +/- 7 to 186 +/- 22 picomoles ATP), 10 micrograms/ml collagen (60 +/- 22 to 449 +/- 53 picomoles ATP and 44 +/- 13 to 219 +/- 25 picomoles ATP in 1- and 4-day platelets, respectively. Ristocetin-induced ATP release increased immediately after transfusion of fresh platelets only (0 +/- 0 to 69 +/- 17) and remained unchanged for 2 h. Fresh platelets also demonstrated greater dense granule release to collagen (5 micrograms and 10 micrograms/ml) and ristocetin than 4-day stored platelets. CONCLUSIONS In patients with chemotherapy-induced thrombocytopenia, platelet transfusion causes an immediate increase in number and function, which is independent of storage time. This quantitative and qualitative increase persists unchanged for 2 h after transfusion, suggesting that there is no acute "warm-up-time" necessary for transfused platelets to regain maximal function. Fresh platelets demonstrate increased aggregation and dense granule release compared to 4-day stored platelets and may impart improved hemostatic function in vivo.