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Background Trauma patients are at high risk for venous thromboembolism (VTE). Opportunity for chemical VTE prophylaxis improvement was identified and practice was altered to start chemoprophylaxis on admission in most patients. The purpose of this study was to determine if early VTE prophylaxis is safe and reduces VTE. Methods The trauma registry was queried over a 12-month period for patients admitted greater than 1 day for traumatic injury. The study spanned 6 months on either side of instituting aggressive chemoprophylaxis. Patients were risk adjusted on demographics, Injury Severity Score, transfusions, procedure type, length of stay, and mortality. Pre-intervention patients were then compared to patients in the aggressive cohort with the primary outcome of VTE. Secondary outcomes included transfusions, mortality, and length of stay (LOS). Results 1597 patients were identified over the study period with 754 (47%) patients in the aggressive period. There were no differences in age, sex, Injury Severity Score, transfusions, procedures, or LOS between cohorts. Pre-algorithm patients were more likely to have penetrating mechanism (9.3% vs 6.6%; P = .009) and longer time to VTE prophylaxis (23.3 vs 13.9 hours; P < .001). No differences were noted in anticoagulant, VTE rate (2.0% vs 1.2%; P = .195), or mortality. Linear regression analysis identified time to chemical prophylaxis as significant predictor of VTE (β = 43.9, P < .001). Conclusions Early aggressive chemical VTE prophylaxis is safe without increasing transfusions. Venous thromboembolism rates were decreased, but did not reach statistical significance.

Background and objectives Pathogen reduction of donor platelets with amotosalen/UVA has been shown to effectively inactivate pathogens and also contaminating white blood cells (WBCs). We wanted to determine whether WBC inactivation could also decrease alloimmune refractoriness to donor platelets. Materials and methods Platelets were prepared from a donor dog's whole blood, and the platelets were either transfused without modification [standard (STD) platelets] or treated with amotosalen/UVA under conditions modelling the amotosalen/UVA Blood System for human platelets (APR) using either 4 or 3 J/cm2 of UVA exposure. Platelets were transfused weekly from a single donor dog for 8 weeks or until the recipient dog became refractory to their donor's platelets. Antibody samples were drawn weekly and tested against the donor dog's platelets and WBCs (CD8 and B cells). Results Only 1/7 (14%) dogs that received STD platelets accepted 8 weeks of donor transfusions. Following APR 4 J/cm2 donor transfusions, 3/9 (33%) recipients accepted their donor's transfusions, but only one recipient remained antibody negative. Following APR 3 J/cm2 donor transfusions, the same dose as used for human platelet transfusions, 7/10 (70%) recipients accepted their donor's transfusions, but only two remained antibody negative. Conclusion As a very high percentage of recipient dogs (70%) accepted APR 3 J/cm2 donor transfusions, these data suggest that preventing alloimmune platelet refractoriness may be another benefit of pathogen reduction using amotosalen/UVA.

Background Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, often fatal complication of blood transfusion that can occur in immunocompromised or immunocompetent recipients and is the result of viable T cells present in the blood components transfused. Study design and methods We examined the TA-GVHD clinical case literature including numerous original clinical case reports and several comprehensive case series. We also evaluated recent in vitro experimental data on the inhibition of T cell proliferation, comparing the effect of a specific pathogen inactivation (PI) technology to that of the Food and Drug Administration-recommended gamma irradiation dose of 2500 cGy. Results We identified 12 published TA-GVHD cases with atypical/milder or delayed symptom presentations and/or an atypical clinical course; these included cases attributed to leukoreduced or suboptimally irradiated units. We summarize recent in vitro data using a sensitive limiting dilution assay that establish that, compared to irradiation at the recommended 2500 cGy dose, PI using amotosalen/ultraviolet A, or amustaline/glutathione achieves a greater degree of inhibition of T cell proliferation. Conclusion We propose that TA-GVHD has a spectrum of disease severity indicating that additional mild cases may still occur but be undiagnosed and/or underreported, opening up the possibility, supported by in vitro experimental data, that irradiation at the currently established dose may not be fully protective. Furthermore, since many US institutions use component irradiation selectively only for immunocompromised patients, immunocompetent recipients are not fully protected. PI technologies appear to be at least equal to, if not better than, gamma irradiation in abrogating the ability of T cells to proliferate, and if applied to all blood components, protection against TA-GVHD would be an additional benefit that would allow for the elimination of component irradiation.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, often fatal complication of blood transfusion that can occur in immunocompromised or immunocompetent recipients and is the result of viable T cells present in the blood components transfused.We examined the TA-GVHD clinical case literature including numerous original clinical case reports and several comprehensive case series. We also evaluated recent in vitro experimental data on the inhibition of T cell proliferation, comparing the effect of a specific pathogen inactivation (PI) technology to that of the Food and Drug Administration-recommended gamma irradiation dose of 2500 cGy.We identified 12 published TA-GVHD cases with atypical/milder or delayed symptom presentations and/or an atypical clinical course; these included cases attributed to leukoreduced or suboptimally irradiated units. We summarize recent in vitro data using a sensitive limiting dilution assay that establish that, compared to irradiation at the recommended 2500 cGy dose, PI using amotosalen/ultraviolet A, or amustaline/glutathione achieves a greater degree of inhibition of T cell proliferation.We propose that TA-GVHD has a spectrum of disease severity indicating that additional mild cases may still occur but be undiagnosed and/or underreported, opening up the possibility, supported by in vitro experimental data, that irradiation at the currently established dose may not be fully protective. Furthermore, since many US institutions use component irradiation selectively only for immunocompromised patients, immunocompetent recipients are not fully protected. PI technologies appear to be at least equal to, if not better than, gamma irradiation in abrogating the ability of T cells to proliferate, and if applied to all blood components, protection against TA-GVHD would be an additional benefit that would allow for the elimination of component irradiation.

INTRODUCTION Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication after transfusion of components containing viable donor T cells. Gamma irradiation with doses that stop T-cell proliferation is the predominant method to prevent TA-GVHD. Treatment with pathogen inactivation methodologies has been found to also be effective against proliferating white blood cells, including T cells. In this study, T-cell inactivation was compared, between amotosalen/ultraviolet A (UVA) treatment and gamma-irradiation (2500 cGy), using a sensitive limiting dilution assay (LDA) with an enhanced dynamic range. METHODS AND MATERIALS Matched plasma units (N = 8), contaminated with 1 × 106 peripheral blood mononuclear cells (PBMCs) per mL, were either treated with amotosalen/UVA or gamma irradiation, or retained as untreated control. Posttreatment, cells were cultured under standardized conditions. T-cell proliferation was determined by the incorporation of 3 H-thymidine and correlated with microscopic detection. RESULTS Range-finding experiments showed that after gamma irradiation (2500 cGy), significant T-cell proliferation could be observed at a 1 × 107 cell culture density, some proliferation at 1 × 106 , and none at 1 × 105 cells/well. Based on these facts, a quantitative comparison was carried out between amotosalen/UVA at the highest challenge of 1 × 107 PBMCs/well, and gamma irradiation at 1 × 106 and 1 × 105 PBMCs/well. Complete inactivation of the T cells after amotosalen/UVA treatment was observed, equivalent to greater than 6.2 log inactivation. Complete inactivation of the T cells was also observed after gamma irradiation when 1 × 105 PBMCs/well were cultured (>4.2 log inactivation). Proliferation was observed when 1 × 106 PBMCs/well were cultured (≤5.2 log inactivation) after gamma irradiation. CONCLUSION Amotosalen/UVA treatment more effectively inactivates T cells than the current standard of gamma irradiation (2500 cGy) for the prevention of TA-GVHD.

Introduction: HSCT patients require platelet components (PC) for support of thrombocytopenia. Donors are tested for selected viruses to prevent transfusion-transmission infection (TTI), and PC are screened for bacteria and irradiated to prevent transfusion associated graft versus host disease (TA-GVHD). Leukocyte reduction (LR) is commonly, but not universally, used to mitigate the risks of acute transfusion reactions (ATR), allo-immunization, clinical refractoriness, and CMV TTI. However, donor testing, PC bacterial screening, and LR do not provide complete protection from ATR, transfusion related sepsis (TRS), refractoriness, CMV TTI, or residual risks of window period and emerging pathogen TTI. Amotosalen-UVA pathogen reduction treatment (A-PRT) inactivates a broad spectrum of pathogens (e.g. Zika), inhibits leukocyte antigen presentation and cytokine synthesis, and inhibits T-cell proliferation. A-PRT with LR has replaced bacterial screening, CMV serology, and gamma irradiation. Objective: To control cost, the Hong Kong Red Cross Blood Transfusion Service (HKRCBTS) has used whole blood platelet-rich-plasma (PRP) PC without LR. Based on data showing effective leukocyte inactivation by A-PRT, the HKRCBTS evaluated use of A-PRT buffy coat PC (BC PC) in platelet additive solution (PAS) without LR, bacterial screening, and gamma irradiation to manage costs, salvage more donor plasma, reduce TTI risk, and simplify production. Study Design and Methods : An open-label, prospective, sequential, two cohort study at Queen Mary Hospital, Hong Kong enrolled HSCT patients for up to 30 days of PC support with 100-day follow up. Cohorts were comparable for primary disease and type of HSCT. The first cohort received PRP PC prepared from CPD whole blood, a current HKRCBTS standard PC (Control-C). Five ABO-matched PRP PCs in 100% plasma were pooled without LR to yield ≥ 3 x 1011 platelets. C-PCs were screened for bacteria, gamma irradiated (2,500 cGy), stored up to 5 days at 22- 24 °C; and contained ~ 5 x 109 leukocytes. For the 2nd cohort, buffy coat PCs (BC PC) were prepared from CPD whole blood in PAS (SSP+, Macopharma, France). Five ABO-matched BC PC in 35% plasma-65% PAS were pooled, and prepared with A-UVA PRT to yield ≥ 3 x 1011 platelets (Test-T). T-PCs were not LR, not screened for bacteria, not gamma irradiated, stored for up to 5 days at 22- 24 °C; and contained ~ 5 x 108 leukocytes. HSCT patients ≥ 18 years expected to require PC were included. Exclusion criteria were: history of clinical refractoriness to platelet transfusion (2 successive 1-HR corrected count increments (CCI) < 5.0 x 103), immune thrombocytopenia, or disorders confounding 1-HR CCI determination. For both cohorts, a transfusion threshold of 10 x 109/L was specified for stable patients unless adjusted to 20 x 109/L for sepsis. Patients were not screened for HLA antibody at study entry. The efficacy outcome was the 1-hour (HR) count increment (CI), and the safety outcome was ATR incidence. Secondary (post-hoc) outcomes were the 1-HR CCI and the incidence of clinical refractoriness (two successive CCI < 5x103 per patient and transfusions with CCI < 5x103). Results: 64 patients were transfused (31 Control and 33 Test). Demographics were similar between cohorts (Table). The majority of patients had allogeneic HSCT from related donors. Mean pre-transfusion platelet counts were < 16 x 109/L. The mean PC dose and storage duration were similar between cohorts (Table). The 1-HR count increments (CI) and 1-HR CCI responses were within therapeutic ranges for both cohorts (Table). The proportion of transfusions with CCI responses < 5.0 x 103 and the proportion of patients with clinical refractoriness were less in the Test cohort (Table). ATRs trended lower with A-PRT (Test = 9.1%, Control = 19.4%, p=0.296).No patients had TRS or TA-GVHD reported during the active transfusion period. Day-100 engraftment (Table), HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts. Conclusions: This exploratory study of A-PRT PC without LR demonstrated therapeutic 1-HR CCI responses, safety, and conserved HSCT engraftment. The proportions of transfusions with CCI < 5.0x103 and the proportion of patients with clinical refractoriness were less for A-PRT PC than conventional PC. A-PRT of pooled whole blood BC PC without LR offers the potential to improve PC supply, and to reduce the net cost of PRT PC by replacing other interventions. Table Table. Disclosures Corash: Cerus Corporation: Employment, Equity Ownership. Liu:Cerus Corporation: Employment, Equity Ownership. Huang:Cerus Corporation: Employment, Equity Ownership. Vermeij:Cerus Corporation: Employment, Equity Ownership. Stassinopoulos:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership.

In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.