Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial.

Pathogen inactivation of platelet concentrates reduces the risk for 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 UV B illumination technology (intervention) compared with 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 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 or higher bleeding in the intention-to-treat analysis: 51% of the transfusion-treatment periods in the control arm and 54% in the intervention arm (95% confidence interval [CI], -6 to 11; P = .012 for noninferiority). However, in the per-protocol analysis, the difference in grade 2 or higher bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI -2 to 18; P = .19 for noninferiority). Transfusion increment parameters were ∼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. This trial was registered at The Netherlands National Trial Registry as #NTR2106 and at www.clinicaltrials.gov as #NCT02783313.

The clinical impact of platelet refractoriness: correlation with bleeding and survival.

BACKGROUND: Despite supportive care with platelet (PLT) transfusions, bleeding complications occur in a substantial number of patients with thrombocytopenia due to cytotoxic therapy. Moreover, refractoriness to PLT transfusions remains a frequently encountered problem. The clinical impact of PLT transfusion failure was investigated in 117 patients, part of a randomized PLT transfusion trial, which excluded patients with HLA and/or HPA alloantibodies. STUDY DESIGN AND METHODS: Between October 2003 and April 2005, a multicenter randomized controlled trial, testing the clinical efficacy of PLTs stored in plasma compared to PLT additive solution (PAS II), was performed. Using multiple regression analysis of observational data of patients randomized in one of the participating centers, the occurrence of PLT transfusion refractoriness was analyzed for a relation with bleeding complications and patient survival. RESULTS: PLT transfusion failure occurred at least once in 49.6 percent of the patients. Mild to moderate bleeding complications occurred in 19 percent of the patients. PLT transfusion failure was, independently from thrombocytopenia, positively associated with bleeding complications (odds ratio, 3.4; 95% confidence interval, 1.1-11). Moreover, patients experiencing one or more 24-hour PLT transfusion failures had, compared to patients always showing a sufficient 24-hour increment, a significantly reduced median survival of 491 days (interquartile range [IQR], 156-858 days) versus 825 days (IQR, 355-996 days), respectively. In a Cox regression model, the effect on survival was independent of therapy, diagnosis, and age. CONCLUSION: Our results suggest that PLT transfusion failure might be a sensitive clinical marker for the occurrence of bleeding and impaired patient survival. PLT transfusion failure, bleeding complications, and decreased survival could be manifestations of a more severe degree of endothelial damage.

A multicenter randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma.

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.