Excessive bleeding is a common and prognostically important complication of cardiac surgery. For bleeding related to coagulation factor deficiency, frozen plasma is the most used therapy. Preliminary trials indicate that 4-factor prothrombin complex concentrate (PCC) may be a suitable alternative. To compare the efficacy and safety of PCC with frozen plasma in patients undergoing cardiac surgery with coagulopathic bleeding. Unblinded randomized noninferiority controlled clinical trial at 12 hospitals in Canada and the US involving adults (≥18 years) who had developed bleeding related to coagulation factor deficiency after termination of cardiopulmonary bypass during surgery (November 30, 2022, to May 28, 2024). Final 30-day follow-up visit was completed on June 28, 2024. A total of 265 patients were randomized to receive PCC (1500 IU ≤60 kg; 2000 IU >60 kg) and 263, frozen plasma (3 U ≤60 kg; 4 U >60 kg) in the operating room. A second dose was allowed over the next 24 hours if indicated; thereafter, only frozen plasma could be used. The primary outcome was hemostatic response (effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation). The noninferiority of PCC vs frozen plasma was assessed using a 10% margin and a 1-sided α of .025, with subsequent testing for superiority if noninferiority was demonstrated. Secondary outcomes included allogeneic blood transfusions and adverse events. Patients were followed up until postoperative day 30. Of 538 enrolled patients, 420 patients (median age, 66 years [IQR, 57-73 years]; 74%, male; 10%, Asian; 1%, Black; and 65%, White) were included in the primary analysis; of those, 296 (70%) underwent complex surgeries. Compared with the 207 patients in the frozen plasma group, the 213 patients in the PCC group had higher hemostatic effectiveness (166 [77.9%] vs 125 [60.4%]; difference, 17.6%; 95% CI, 8.7%-26.4%; P < .001 for noninferiority and superiority) and had received fewer transfusions including red blood cells, platelets, and noninvestigational frozen plasma units (mean, 6.6 units; 95% CI, 5.7-7.7 vs 9.3 units; 95% CI, 8.0-10.8; difference, 2.7; 95% CI, 1.0-4.4; P = .002). Seventy-seven patients (36.2%) in the PCC group vs 98 (47.3%) in the frozen plasma group experienced serious adverse events (relative risk [RR], 0.76; 95% CI, 0.61-0.96; P = .02). Twenty-two patients (10.3%) in the PCC group and 39 (18.8%) in the frozen plasma group had acute kidney injury (RR, 0.55; 95% CI, 0.34-0.89; P = .02). In this unblinded randomized clinical trial, PCC had superior hemostatic efficacy and safety advantages to frozen plasma among patients requiring coagulation factor replacement for bleeding during cardiac surgery. ClinicalTrials.gov Identifier: NCT05523297.

Platelet transfusion is a lifesaving medical procedure in contexts ranging from hemorrhagic bleeding to chemotherapy. However, platelet supply, shelf life, and quality remain challenging problems for blood banks globally. Platelets have limited shelf lives throughout which their quality rapidly degrades, a phenomenon known as the platelet storage lesion (PSL). Another longstanding and life-threatening complication of platelet transfusion and storage is bacterial contamination and growth, leading to infection and sepsis post-transfusion. These challenges result in high wastage rates of platelets (~20% in Canada) and chronic shortages globally. Furthermore, current state-of-the-art pathogen reduction and antiseptic technologies cannot consistently eliminate all bacteria present in platelet concentrates. To address these challenging problems, this research aims to develop next-generation platelet storage bags capable of self-sterilizing from bacteria while extending platelet shelf life, thereby improving the supply, safety, and efficacy of platelet transfusions. To address these challenging problems, this project aims to develop next-generation blood storage bags capable of eliminating bacteria while extending the blood's shelf life. We have developed a line of universally applicable coatings based on the co-assembly of polydopamine with a library of ultra-high molecular weight hydrophilic polymers (uHHPs) in water that prevent both platelet and bacterial adhesion on storage units. These coatings can be deposited in one step in water, and do not leach, providing a practical approach do developing bioactive coatings with widespread functionality that can be deposited on myriad materials in medical devices, including blood storage bags. Our group has screened a wide library of UHHPs for the polydopamine coatings and identified 3 coatings that demonstrate excellent long-term biocompatibility with platelet concentrates, showing no significant decreases in quality markers when compared to industry-standard storage bags (metrics including CD62P and phosphatidylserine display, blood gas analysis of O2, CO2, pH, glucose, and lactate, rotational thromboelastometry using EXTEM and INTEM, or aggregometry with ADP, thrombin, or TxA2). Proteomic characterization of the protein coronas formed on the surface of the uncoated and coated bags revealed stark differences in surface proteomes, yet notably, these did not manifest in differences in platelet storage quality, suggesting that the species and quantity of proteins adhered does not impact platelet storage quality. Using the platelet-compatible coatings, we have developed blood storage bags conjugated with novel antimicrobial peptides (AMPs), identified through a library screen, that render the blood bags self-sterilizing. Platelet concentrates coated with AMP-coupled coatings using the AMPs E6- and Tet20 eliminated 100 CFU/mL Staphylococcus epidermidis 24 h, with no significant decreases in quality for platelets in coated units, whether the bags were inoculated with bacteria or not. Coated bags containing leukoreduced whole blood reduced S. epidermidis growth and did not demonstrate significant decreases in quality either. Collectively, this data is a proof-of-concept that AMP-coupled coatings can act as a platform for the development of self-sterilizing blood bags. The development of a next-generation platelet storage bag capable of self-sterilization holds immense promise for blood banking systems globally, as platelet shortages remain a chronic challenge and blood contamination persists despite best efforts. Furthermore, this technology may act as the basis for the development of future bioactive platelet storage bags that actively combat the PSL or combat other relevant bloodborne pathogens.

The accumulation of uremic toxins, a hallmark of kidney failure in hemodialysis-dependent patients, highlights hemodialysis's limits to effectively removing a broad range of toxins. Adsorption-based strategies have emerged as a promising solution. However, a critical gap remains in understanding the hemocompatibility of these materials in the context of kidney failure. In this study we investigated the hemocompatibility and protein adsorption behavior of α-, β-, and γ-cyclodextrin-coated magnetic nanoparticles in modeled uremic plasma and blood. Cyclodextrin-coated nanoparticles exhibited greater protein adsorption compared to untreated plasma, while cyclodextrin-modified particles showed significantly reduced protein adsorption per unit surface area compared to bare nanoparticles. Immunoblotting revealed distinct protein adsorption profiles compared to untreated plasma, where an increased trend in surface adsorption was observed for most plasma proteins in uremic plasma, with substantial changes in the binding of complement proteins, fibrinogen, α2 macroglobulin, fibronectin, protein S, and immunoglobulins. We did not observe any clear indications of hemo-incompatibility of the cyclodextrin-coated magnetic nanoparticles under uremic conditions in whole blood. Interestingly, we also found some evidence of improved platelet responsiveness and clot formation time with magnetic nanoparticle treatment, under uremic conditions. These findings underscore the potential of cyclodextrin-coated magnetic nanoparticles for safer, more efficient blood detoxification strategies in kidney failure.

Background: Platelets are an essential component of hemorrhage control and management, and engineering platelets to express therapeutic proteins could expand their use as a cell therapy. Genetically engineered platelets can be achieved by modifying the platelet precursor cells, megakaryocytes (MKs). Current strategies include transfecting MK progenitors ex vivo with viral vectors harboring lineage-driven transgenes and inducing the production of in vitro modified platelets. The use of viruses, however, poses challenges in clinical implementation, and no methods currently exist to genetically modify MKs with nonviral techniques. Lipid nanoparticles (LNPs) are a nonviral delivery system that could enable a facile strategy to modify MKs with a variety of nucleic acid payloads. Objectives: To investigate whether LNPs can transfect cultured hematopoietic stem/ progenitor cell-derived MKs to express exogenous proteins and induce functional changes. Methods: MK and MK progenitors differentiated from cord blood-derived hematopoietic stem/progenitor cells were treated with LNP formulations containing messenger RNA and resembling the clinically approved LNP formulations. Transfection efficiency was assessed through flow cytometry by expression of enhanced green fluorescent protein. Functional changes to the MKs were assessed through rotational thromboelastometry by expression of exogenous coagulation factor (F)VII, a representative physiologically relevant protein. Results: LNPs enabled transfection efficiencies of 99% in MKs and did not impair MK maturation, viability, and morphology. MKs engineered to express exogenous FVII decreased clotting time in FVII-deficient plasma following clot initiation. Conclusion: This approach provides an easy-to-use modular platform to genetically modify MK and MK progenitors, which can be potentially extended to producing genetically modified cultured platelets.

Platelet transfusion is an indispensable therapy used in contexts ranging from hemorrhagic bleeding to chemotherapy. However, platelet shelf life and quality deteriorate during storage in a process termed the platelet storage lesion (PSL), resulting in chronic shortages globally. The PSL is thought to be partially attributed to the bio-incompatible polyvinyl chloride (PVC) storage bags that promote protein fouling and platelet adhesion. Developing platelet-friendly materials is therefore essential for improving platelet storage quality. This study aimed to delineate the contributions of protein adsorption and platelet adhesion to the progression of the PSL. Hydrophilic coatings are screened to identify those which resist protein and platelet adhesion most effectively. These coatings are translated into mini-platelet bags and tested in long-term standard blood banking conditions. Significant reductions in platelet adhesion after 7-day storage do not affect platelet quality. Proteomic characterization of the bag surfaces revealed dynamic changes in the protein coronas on coated and uncoated bag over time, but are uncorrelated with platelet quality. This research demonstrates a method to identify platelet-compatible coatings suitable for long-term storage, as well as a novel approach to characterize the surface of blood storage bags.

BACKGROUND AND OBJECTIVES:With the rising prevalence of diabetes and expanded blood donor criteria in Canada, individuals with diabetes are increasingly contributing to the blood supply. However, little is known about how routine manufacturing affects red blood cells (RBCs) from this group. This study examined RBC differences in donors with type 1 (T1D) or type 2 diabetes (T2D) following processing to generate red cell concentrates (RCCs). MATERIALS AND METHODS:Whole blood (WB) donations were collected from voluntary T1D (n = 12), T2D (n = 11) and non-diabetic age/sex-matched (n = 23) donors. Donations were processed via red cell filtration to generate RCCs. At donation, 2.7-mL of WB was collected into EDTA tubes, and 70 mL of processed RCCs was aliquoted into satellite bags. WB-EDTA tubes and RCC satellite bags were characterized on Day 2 post collection. RESULTS:Donors with T1D and T2D had similar, but higher glycated haemoglobin (HbA1c) levels than matched controls (p < 0.001). Processing increased RBC count, haemoglobin and haematocrit in all groups (p < 0.0001). Donors with T2D had decreased mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) compared to controls, both pre and post processing (p < 0.05), with a similar trend in p50 (pre: p < 0.01; post: p < 0.05). CONCLUSION:Blood component manufacturing did not exacerbate stress on RBCs from donors with diabetes. Donors with T2D had altered MCH, MCHC and p50 compared to matched controls, which persisted after processing. These findings emphasize the importance of donor health on blood product quality.

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.

Major traumatic hemorrhage is now frequently treated by early hemostatic resuscitation on hospital arrival. Prehospital hemostatic resuscitation could therefore improve outcomes for bleeding trauma patients, but there are logistical challenges. Freeze-dried plasma (FDP) offers indisputable logistical advantages over conventional blood products, such as long shelf life, stability at ambient temperature, and rapid reconstitution without specialized equipment. We sought high level, randomized, controlled evidence of FDP clinical efficacy in trauma. A structured systematic search of MEDLINE/PubMed was carried out and identified 52 relevant English language publications. Three studies involving 607 patients met our criteria: Resuscitation with Blood Products in Patients with Trauma-related Hemorrhagic Shock receiving Prehospital Care (RePHILL, n = 501); Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock (PREHO-PLYO, n = 150); and a pilot Australian trial ( n = 25). RePHILL found no effect of FDP plus packed red blood cells (PRBC) concentrate transfusion versus saline on mortality. PREHO-PLYO found no effect of FDP versus saline on International Normalized Ratio (INR) at hospital arrival. The pilot trial found that study of PRBC versus PRBC plus FDP was feasible during long air transport times to an Australian trauma centre. Further research is required to determine under what conditions FDP might provide prehospital benefit to trauma patients. (c) 2023 Elsevier Inc. All rights reserved.

Platelets contribute to a variety of physiological processes including inflammation, sepsis and cancer. However, due to their primary role in hemostasis, platelet transfusions are largely restricted to managing thrombocytopenia and bleeding. One way to expand the utility of platelet transfusions would be to genetically engineer donor platelets with new or enhanced functions. We have previously shown that lipid nanoparticles containing mRNA (mRNA-LNP) can be used to genetically modify authentic platelets in a non-clinical crystalloid solution. Currently, platelets collected for transfusion are stored in plasma or in plasma supplemented with platelet additive solution (PAS) at supraphysiological concentrations at room temperature, or at 4 ºC if intended for use in acute hemorrhage. Here we describe a new plasma-optimized mRNA-LNP for transfecting platelets directly in plasma and plasma supplemented with PAS that is scalable to physiological and supraphysiological platelet concentrations. Transfecting platelets in clinical solutions with mRNA-LNP does not affect aspects of in vitro physiology, and transfected platelets are storable. The compatibility of this transfection system with current clinical practices could enable future mRNA-LNP based platelet products and cell therapies.

BACKGROUND:Fetal and neonatal exposure to lead is associated with irreversible adverse effects on neural development. There is no reliable threshold for lead effect, so limiting exposure is recommended. A significant correlation has been reported between post-transfusion blood lead level (BLL) in infants and lead levels in transfused RBC units. We measured levels of lead, mercury, and cadmium, in Canadian donor blood to investigate if concerning levels for neonatal transfusion exist. STUDY DESIGN AND METHODS:Whole blood samples from blood donors (n = 2529) were shipped cold within 7 days of donation. All permanent blood donation clinics across Canada were sampled. Twelve of these permanent clinics and 8 mobile clinics with a greater potential for having higher lead or mercury levels were oversampled. Heavy metals were measured by inductively coupled plasma mass spectrometry. RESULTS:Of all donations, 2.2% (lead) and 0.4% (mercury) had levels higher than the recommended thresholds for safe neonatal transfusion. BLLs were higher in males but there was no significant difference in the blood mercury levels of males versus females. Cadmium levels were higher in females. There was a positive correlation between donor age and levels of heavy metals, with lead having the strongest correlation (r = 0.47, p < .0001). Three clinics in close proximity to two lead-producing mines were among the clinics with the highest BLLs. Significantly higher blood mercury levels were observed in coastal clinics. CONCLUSION:Our data on donor blood heavy metal levels supports considering blood transfusion as an exposure source to heavy metals and encourages informed selection of blood units for transfusion to vulnerable groups.

Cold-stored (CS) platelets are once again being reintroduced for clinical use. Transfused CS platelets offer benefits over room temperature-stored (RTS) platelets such as increased hemostatic effects and prolongation of shelf-life. Despite these advantages little is known about their association with transfusion-related acute lung injury (TRALI). TRALI is associated with prolonged storage of RTS platelets and has a mortality of >15%. Determining the safety of CS platelets is important considering their proposed use in TRALI-vulnerable populations with inflammation such as surgical patients or patients with trauma. Donor platelet-derived ceramide causes TRALI, whereas donor platelet sphingosine-1-phosphate (S1P) is barrier protective. Females have higher plasma levels of S1P than males. Cold temperatures increase S1P levels in cells. Therefore, we hypothesized that female (donors or recipients) and/or CS platelets would decrease TRALI. To test this, we compared how male and female donor and recipient allogeneic platelet transfusions of CS (4°C) versus RTS (23°C) platelets stored for 5 days influence murine TRALI. Transfusion of CS platelets significantly reduced recipient lung tissue wet-to-dry ratios, bronchoalveolar lavage total protein, lung tissue myeloperoxidase enzyme activity, histological lung injury scores, and increased plasma sphingosine-1-phosphate (S1P) levels compared with RTS platelet transfusions. Female as opposed to male recipients had less TRALI and higher plasma S1P levels. Female donor mouse platelets had higher S1P levels than males. Mouse and human CS platelets had increased S1P levels compared with RTS platelets. Higher recipient plasma S1P levels appear protective considering females, and males receiving platelets from females or male CS platelets had less TRALI.NEW & NOTEWORTHY Transfusion-related acute lung injury (TRALI) though relatively rare represents a severe lung injury. The sphingolipid sphingosine-1-phosphate (S1P) regulates the severity of platelet-mediated TRALI. Female platelet transfusion recipient plasmas or stored platelets from female donors have higher S1P levels than males, which reduces TRALI. Cold storage of murine platelets preserves platelet-S1P, which reduces TRALI in platelet-transfused recipients.

Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.

BACKGROUND AND OBJECTIVES:Plasma has become an essential ingredient for various medical treatments. Many blood collection agencies rely on voluntary non-remunerated donation when collecting plasma, but at present many do not collect sufficient plasma to meet domestic demands. This rapid review sought to explore the factors that have been found to influence people's decisions to donate plasma to inform future research. METHODS:Searches were conducted in PubMed, PsycINFO, Social Sciences Citation Index and CINAHL for peer-reviewed journal articles that discussed plasma donation and the factors associated with donor behaviour. Pertinent information from included articles was extracted and arranged in themes. RESULTS:In total, 33 articles were included in this review. Three main themes were identified by the authors. The first focused on site-level factors related to blood collection agencies' engagement with plasma donors and their influence on plasma donation experiences. The second theme considered how individual characteristics and experiences influence willingness to donate plasma. The third theme examined social and cultural-level factors, such as how social networks and community shape perceptions and experiences with donation. CONCLUSION:Our findings suggest that the current understanding of plasma donation is focused mainly on converting whole blood donors and also centres on individual-level factors to donation. Further research must examine what factors attract non-whole blood donors to become plasma donors, focusing on broader social-level influences. This review will inform policies and interventions for blood collection agencies to increase plasma donors.

BACKGROUND:In 2021, Canada implemented a pilot plasma program allowing some sexually active men who have sex with men (including but not limited to gay and bisexual men; gbMSM) to donate plasma. Changes to plasma donation policy could help address inequities in access to plasma donation and increase Canada's domestically collected plasma supply if more gbMSM donate as a result. We aimed to (1) examine views regarding plasma donation and the pilot program prior to implementation and (2) identify modifiable theory-informed predictors of gbMSM's intention to donate plasma.METHODS:We developed, piloted, and disseminated a questionnaire informed by the Theoretical Domains Framework (TDF). We recruited gbMSM in London (ON) and Calgary (AB) to an anonymous, online cross-sectional survey.RESULTS:A total of 246 gbMSM completed the survey. On scales from 1 (strongly disagree) to 5 (strongly agree), general intention to donate was high (mean = 4.24; SD = 0.94). The pilot program itself was mostly acceptable (mean = 3.71, SD = 1.16), but the intention to donate under the unique requirements of the pilot program was lower than general intention (mean = 3.58; SD = 1.26). Two domains from the theoretical domains framework (TDF) (beliefs about consequences of donating plasma and social influences) were independently associated with general intention to donate.DISCUSSION:The pilot plasma program as an incremental step toward more inclusive policies was mostly viewed as acceptable by the impacted communities. Historical and ongoing exclusions create unique barriers to donation. There are clear opportunities for developing theory-informed interventions to support gbMSM to donate plasma as policies continue to become more inclusive and more become eligible to donate.

BackgroundCanada has incrementally reduced restrictions to blood and plasma donation that impact men who have sex with men, gay, bisexual, and queer men, and some Two Spirit, transgender and non-binary individuals (MSM/2SGBTQ+). Prior to the launch of a pilot program in 2021 enabling some MSM/2SGBTQ + to donate source plasma, we explored the acceptability of the program among individuals who could become eligible to donate in the program.MethodsWe invited men identifying as MSM/2SGBTQ + to participate in two consecutive semi-structured interviews to explore their views on blood and plasma donation policy, plasma donation, and the proposed Canadian plasma donation program. Interview transcripts were analyzed thematically and acceptability-related themes were mapped onto the Theoretical Framework of Acceptability.ResultsTwenty-seven men identifying as having sex with men participated in 53 interviews. Eighteen themes were mapped onto the seven construct domains of the Theoretical Framework of Acceptability. Underlying all aspects of acceptability was a tension between four primary values influencing participants' views: altruism, equity, supply sufficiency, and evidence-based policy. The program was viewed as welcome progress on a discriminatory policy, with many excited to participate, yet tension with inequitable aspects of the program undermined support for the program and interest to contribute to it. The high demands of the program are unique for MSM/2SGBTQ + and are only tolerable as part of a program that is an incremental and instrumental step to more equitable donation policies.ConclusionFindings highlight past experiences of exclusion in Canada as a unique and critical part of the context of the donation experience among MSM/2SGBTQ+. Despite the program's goals of greater inclusivity of MSM/2SGBTQ + individuals, the anticipated experience of the program included continued stigmatization and inequities. Future research should seek to understand the experienced views of MSM/2SGBTQ + donors to ensure that as policies change, policies are implemented equitably.

Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.

405 nm light is less toxic on the host cells while effective in killing microbes. To date, the violet-blue light has been shown to be effective against several blood-borne pathogens including bacteria, HIV-1, and Trypanosoma cruzi. Study Design/Methods: Apheresis-collected human platelets concentrates (PCs) stored in plasma, from six screened donors were used. The FDA Research Involving Human Subjects Committee approved the use of human platelets for the research. Platelets from three donors were each inoculated with Leishmania donovani promastigotes at high titer (10E6/mL). Six Teruflex T-150 transfer bags containing 40 mL each of parasite-spiked platelets were prepared per donor. Three bags were used as controls (no 405 nm light exposure wrapped in tinfoil) and other three bags were treated with the light at an irradiance of 54 J/cm/h for 5 h. Similarly, three PCs from a separate set of donors were inoculated with lower titer of parasites (10E3/mL) reflecting a physiological parasitemia level. All bags were placed in a closed LED source emitting narrowband 405 nm light, and maintained at 22°C, on a shaker incubator set at 60 rpm. Ten samples from each bag at 0 hr and 5 hr time points were enumerated for viable parasites using Neubauer hematocytometer chamber. Results/Findings: Relative to controls, in the high titer-spiked 5-h light-treated samples, parasite counts were near zero, suggesting parasite inactivation. Similar results were observed with lower titer-spiked 5-h lighttreated samples. The observed parasite inactivation associated with 5 hrs light treatment demonstrates that the treatment was able to exert microbicidal effect on Leishmania in ex vivo platelets. Based on previous reports, this is perhaps achieved through photoexcitation of porphyrins and flavins present in the plasma which induces reactive oxygen species (ROS) that cause damage to pathogens. Conclusions: This study revealed promising microbicidal role of the violet-blue light on Leishmania in ex vivo platelets stored in plasma and warrants further studies involving in vivo animal model to validate the results obtained from in vitro experiments.