Adult, but Not Neonatal, Platelet Transfusions Drive a Monocyte Trafficking Phenotype in Vitro and In Vivo

Although, thrombocytopenia can affect all age groups, neonates, especially pre-term, have an increased incidence of thrombocytopenia. Platelet transfusions may reduce the bleeding risk in neonates, but are also associated with adverse short and long-term immune and inflammatory outcomes. A randomized trial of platelet transfusions in neonates found that transfusion was associated with an increased risk of necrotizing enterocolitis, unilateral/bilateral retinopathy, and bronchopulmonary dysplasia. Past work from our research team found that neonatal platelets expressed lower levels of mRNA for many immune related molecules compared to adult platelets. We therefore sought to determine whether the transfusion of adult platelets to neonates resulted in developmental immune dysregulation, with a focus on platelet and monocyte interactions. To explore the interactions between monocytes and platelets, we isolated monocytes from adult mouse bone marrow and co-incubated monocytes with adult (>8 weeks old) or neonatal mouse platelets (7 days old mice) and determined inflammatory and trafficking monocyte phenotypes by flow cytometry and qRT-PCR. Monocytes treated with adult platelets had an increased inflammatory (Ly6C hi) and trafficking phenotype (CCR2 hi), while monocytes treated with neonatal platelets adopted an inflammatory, but not trafficking phenotype. As expected, adult platelets increased the expression of monocyte inflammatory (Nos2, Cxcl1, Ccl2) and trafficking (Ccr2) mRNA, while neonatal platelets also increased inflammatory mRNA expression, but did not increase Ccr2 expression. Adult platelets express more Selp (P-selectin) than neonatal platelets and P-selectin is a major mediator of platelet and monocyte interactions. We confirmed that adult platelets expressed more P-selectin protein compared to neonatal platelets, and found that blocking P-selectin decreased adult platelet induced CCR2 expression to levels similar to monocytes treated with neonatal platelets. Using a transwell chamber we assessed adult and neonatal platelet effects on monocyte migration towards the CCR2 ligand CCL2. Monocytes were treated with adult platelets had significantly greater monocyte migration compared to monocytes co-incubated with neonatal platelets. To model platelet transfusions in the setting of thrombocytopenia, we used 14d old thrombopoietin receptor knockout mice (TPOR -/-) that have low platelet counts, and infused adult or neonatal platelets. We observed a significant increase in inflammatory and trafficking monocytes in mice transfused with adult platelets compared to those transfused with neonatal platelets. Using an in vivo model of monocyte chemotaxis, mice were treated with CCL2 intraperitoneal after platelet transfusion. Adult platelet transfusions, but not neonatal, increased monocyte peritoneal trafficking to CCL2. These data provide comparative insights as to how adult and neonatal platelet transfusions regulate monocyte functions. Adult platelet transfusions to neonates are associated with an inflammatory and trafficking monocyte phenotype that is platelet P-selectin dependent and may have a major impact on neonatal platelet transfusion complications. Disclosures Palis: Rubius Therapeutics: Consultancy.

Platelet Transfusions Can Increase or Decrease the Inflammatory Response and Mortality in a Murine Model of Neonatal Polymicrobial Sepsis

Thrombocytopenia affects 18-35% of all neonates in the Neonatal Intensive Care Unit and ~70% of those born extremely prematurely, with sepsis being a frequent cause. Platelet transfusions (PTx) are frequently given to septic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding risk. However, in the largest randomized trial of neonatal PTx thresholds, infants transfused at a higher PC threshold had a significantly higher mortality and/or major bleeding compared to infants transfused at a lower threshold. We hypothesized that the deleterious effects of PTx would be related to a potential "developmental mismatch" resulting from adult platelets being transfused into a neonate. Among other developmental differences, adult platelets (human and murine) exhibit significantly higher surface P-selectin expression following activation than neonatal platelets. P-selectin is essential for the interaction of platelets with immune cells. Thus, we hypothesized that adult platelets transfused into septic neonates would be consumed faster than endogenous neonatal platelets (due to higher potential for immune interaction), and would increase inflammation and mortality. To test these hypotheses, we used a published murine model of neonatal sepsis, consisting of injecting cecal slurry (CS) into C57BL/6 pups. CS batches were prepared by isolating the cecal content of adult C57BL/6 mice, which was weighted, aliquoted and frozen until use. Three different CS batches were prepared and injected IP into post-natal day 10 pups at a dose of 1.1 (CS1) or 1.0 mg/g (CS2 and 3). Two hours after infection, pups were transfused with washed platelets from adult GFP mice (5x10 7 platelets/g) or Tyrode's buffer (control). Weights, PCs and GFP platelet % were measured before, 4h and 24h post-infection. Blood was collected via terminal bleed at 24h, and plasma separated for quantification of 31 cytokines by multiplex. Despite identical preparation, CS batches varied greatly in their 24h mortality (11% vs 73% vs. 30% for CS1, 2 and 3, respectively). Moreover, PTx had different effects on the mortality of pups infected with different CS batches, increasing the 24h mortality of pups infected with CS1 (30% in transfused vs 11% in non-transfused, RR 2.70, 95% CI 1.02-7.15) but decreasing the mortality of pups infected with CS2 (46% vs. 73%) or CS3 (9% vs. 30%), with a combined RR of 0.52; 95% CI 0.30-0.91. Bacterial counts differed between CS batches, but did not correlate with mortality. Comparison of the microbiome composition using deep sequencing revealed an increased presence of pathogenic bacterial species (Legionella, Sutterella, and Helicobacter species) in CS2 and 3 compared to CS1, and a relative abundance of beneficial bacterial (Actinobacteria and Proteobacteria) in CS1. Different CS batches also elicited different cytokine responses, with significant differences noted in G-CSF, IL-1α, IL-1β, IL-3, IL-7, IL-12p70, and IL-15 levels (p<0.05). For all of these cytokines, except G-CSF, levels were lower in mice infected with CS1 compared to CS2 or 3. Next, we investigated the effects of PTx on the plasma cytokine profile of mice infected with CS1 or CS2/3 (combined), compared to their infected, non-transfused littermates. For nearly all cytokines, PTx increased the response after infection with CS1, but decreased it after infection with CS2/3, with a significant difference in mean global cytokine effect (p<0.0001). For individual cytokines, however, these differences only reached statistical significance for LIX (CXCL5, p=0.04) and approached significance for IL15 and IL17 (p=0.06). Finally, we developed a mathematical model to compare the consumption of endogenous neonatal platelets (GFP-) to that of transfused adult platelets (GFP+) in pups infected with CS1 vs. CS2. In both, the calculated percent consumption was higher for adult platelets than for neonatal platelets (54.8% vs. 32.6% for CS1 and 56.5% vs. 40.4% for CS2). In conclusion, our findings support the hypothesis that adult transfused platelets are consumed faster than endogenous platelets in early neonatal sepsis, and demonstrate that platelet transfusions can either enhance or attenuate the neonatal inflammatory response and the mortality in a model of murine polymicrobial sepsis, depending on the bacterial composition of the inoculum and/or the severity of the sepsis. Disclosures Stowell: Grifols: Speakers Bureau; Argenx: Speakers Bureau; Alexion: Consultancy.

Can We Lower the Platelet Threshold of ≥50x10 9/L for Performing a Lumbar Puncture Safely in Patients with Hematological Malignancies?

Introduction: Lumbar punctures (LP) are routinely used to administer intrathecal chemotherapy for children and adults with hematologic malignancies. The platelet threshold at which an LP can be safely performed is a heavily debated topic. A platelet count of ≥50x10 9/L is a widely accepted threshold for other image-guided procedures [1]. In this patient population achieving this platelet count can be challenging. Previous studies failed to report any increase in the incidence of post-procedure adverse events in patients with a platelet count below this threshold who undergo LPs [2,3,4]. However, these prior studies were limited in their sample size for the number of LPs done in patients with platelets <50 x 10 9/L. Objective: Our study aims to identify differences in adverse events related to the administration of intrathecal chemotherapy in patients with platelet counts <50 x10 9/Lcompared to those over the transfusion threshold of ≥50x10 9/L. Methods: A retrospective chart review of all patients who received intrathecal chemotherapy under fluoroscopy guidance between January 2020 and May 2021 at Moffitt Cancer Center was performed. Patient charts were reviewed to collect information on baseline characteristics, laboratory parameters, platelet transfusions, and post-procedure outcomes. Adverse events related to LPs or platelet transfusions were compared among patients above or below the platelet threshold of 50x10 9/L. Statistical analysis was performed using chi-square test. Results: A total of 900 LPs performed on 224 unique patients were included in the study. The median age at LP was 60 years (range 20-87). 107 (47.7%) patients were females and 117 (52.3%) were males. 169 (75.5%) patients were Caucasian, 22 (9.8%) African American, 3 (1.3%) Asian, 3 (1.3%) Hispanic, and 27 (12.1%) were unknown. The hematological malignancies for which intrathecal chemotherapy was administered included: acute lymphoblastic leukemia, diffuse large B cell lymphoma, other B-Cell Lymphomas, acute myeloid leukemia, T-cell lymphomas, blast-phase chronic myeloid leukemia, mixed phenotype acute leukemia, and chronic lymphocytic leukemia (Table 1, Figure 1). The 900 LPs were divided into two cohorts based on the pre-procedure platelet count: Cohort 1 included 682 LPs (75.8%) with a pre-procedure platelet count ≥50x10 9/L, and cohort 2 included 218 LPs (24.2%) with a pre-procedure platelet count <50x10 9/L. The average laboratory parameters for the cohorts are presented in Table 2. The average platelet counts for cohort 1 and cohort 2 were 199 (range 50-838) and 32 (range 15-49), respectively. Patients with a pre-procedure platelet count of <50x10 9/L were transfused at a significantly higher rate prior to the procedure (55% vs 4.5%, p<0.0001). Only one patient experienced an adverse reaction from platelet transfusion in the form of allergic reaction with facial swelling, treated and resolved with diphenhydramine. A total of 59 post-procedure adverse events were reported but were not significantly different between the two groups (6.5% vs 6.8%, p=0.8237). No instances of epidural hematomas were reported. The most common complications included headaches (n=42), back pain or soreness (n=11) and nausea or vomiting (n=6). Only two patients experienced bleeding complications, including subarachnoid hemorrhage and subdural hemorrhage, but neither of these was directly linked to the procedure. However, the rate of traumatic taps was significantly higher in the group with platelets <50x10 9/L with observed LP RBC count ≥200 (31.2% vs 20.5%, p=0.0016), ≥500 (27.1% vs 14.6%, p<0.0001), and ≥1000 (23% vs 11.6%, p<0.0001). Conclusion: Among 900 LP procedures, a pre-procedure platelet count <50x10 9/L did not demonstrate a higher rate of hemorrhagic complications (6.5% vs 6.8%, p=0.8237) but did demonstrate a higher rate of traumatic taps. No instances of epidural hematomas were seen. However, the number of pre-procedure platelet transfusions required was higher in the group with lower platelets. In light of this, consideration should be given to lowering the platelet threshold for performing LPs. While prospective studies are necessary to confirm that a lower platelet threshold is safe, a lower platelet threshold would result in decreased burden on blood banks by reducing platelet transfusions and could potentially aid in decreasing platelet alloimmunization and subsequent sequelae. Figure 1 Figure 1. Disclosures Jaglal: Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Retrospective Review of Transfusion Practices in a Single Neonatal Intensive Care Unit (NICU) Compared to Recent Transfusion Guidelines

Background Platelet and packed red blood cell (pRBC) transfusion practices for preterm infants vary significantly worldwide. Recent randomized trials of preterm infants receiving platelet or pRBC transfusions have not shown any benefit with higher compared to lower transfusion thresholds. In the recent PlaNeT2 study published in January 2019, infants receiving platelets at higher thresholds had significantly higher rates of death and major bleeding. These findings raise concern about transfusing adult platelets into a delicately balanced neonatal hemostatic system with relatively hypofunctional platelets as a potential etiology of this multifactorial outcome. In this retrospective review, we aimed to review transfusion practices and outcomes, including thrombosis, in the neonatal intensive care unit (NICU) at the University of Arizona, Tucson in comparison to the PlaNeT2 study. Methods After Institutional Review Board approval, we reviewed the electronic medical records of all neonates born at < 32 weeks gestation in the NICU or transferred to the NICU within 48 hours of birth between January 1, 2018 and December 31, 2019, corresponding to one year pre- and one year post-publication of the PlaNet2 study. For each patient record reviewed, we collected demographics, reviewed whether transfusions occurred, and documented pre-transfusion hemoglobin, platelet count, international normalized ratio, fibrinogen activity level, and clinical outcomes. We recorded the number of transfusions of each product, clinical central lines placed, and imaging studies performed to detect thrombosis. These data were analyzed using descriptive analysis. Results There were 127 neonates born <32 weeks gestation, all of whom were analyzed. Twenty-eight (35%) of neonates were born at <27 weeks' gestation and twenty-two (17%) were <1500 g at birth and were considered high risk infants. Seventy three percent of these patients were intubated at some point during their NICU admission. The majority of patients had bronchopulmonary dysplasia (63%). Ten patients developed necrotizing enterocolitis (7.8%), 28 had presumed or confirmed sepsis (22%), 52 had congenital heart disease (41%), and 12 had retinopathy of prematurity (9.4%). During the two-year period of this review, 60% of patients had at least one pRBC transfusion, 13% of patients had at least one platelet transfusion, and 6% of patients had at least one fresh frozen plasma (FFP) transfusion. A total of 35 platelet, 370 pRBC, and 11 FFP transfusions were administered with a mean total of 3.3 total transfusions per patient. The mean and median pre-transfusion platelet counts were 79,300/uL and 52,000/uL, respectively. The mean and median pre-transfusion hemoglobin values were 12.1 g/dL and 12.2 g/dL, respectively. Only two of 35 platelet transfusions were given after the publication of the PlaNeT2 study in January 2019; however, both transfusions were given for neonates with pre-transfusion platelet counts >50,000/uL. There were no arterial or venous thrombosis events noted in our population even though 108 patients (85%) had a peripherally inserted central catheters for an average of 12 days, 32 (25%) had umbilical arterial catheters for an average of 7 days, and 66 (52%) had umbilical vein catheters placed for an average of 6 days. Conclusions The majority of transfusions given to neonates born at <32 weeks gestation at the University of Arizona, Tucson institution over a two-year retrospective study period were pRBC transfusions with an incidence of 0.6 followed by platelet transfusions (incidence of 0.13) and FFP. Platelet transfusion practices changed drastically following publication of the PlaNet2 study, with only 2 of 35 (5.7%) platelet transfusions given after the publication of this study. No thrombotic events were documented in the study population despite a high prevalence of central venous lines and a mean pre-platelet transfusion threshold of 79,300/uL. Transfusion practice guidelines can affect clinical practices in the NICU and can potentially minimize risks. Larger prospective studies are needed to evaluate risk of thrombosis related to adult platelet transfusions given to neonates. Disclosures No relevant conflicts of interest to declare.

Large Population Dataset Linkage to Understand Evolving Practice in Red Cell and Platelet Transfusion and Clinical Outcomes in Patients with Myelodysplastic Syndromes (MDS): A 15-Year Study

Aim: Transfusions are frequently administered for anemia and thrombocytopenia in MDS. However, evidence to guide transfusion remains sparse, along with data about real-world MDS transfusion practices, transfusion-related outcomes and changes over time with increasing access to disease-modifying therapies. In Australia, from 2011, 5-azacitidine was funded through the Pharmaceutical Benefit Scheme (PBS) for patients with IPSS classification intermediate-2 or high-risk MDS, or Chronic Myelomonocytic Leukemia-2 (CMML-2). Australian Patient Blood Management (PBM) guidelines were also first published in 2011. We aimed to characterise red blood cell (RBC) and platelet transfusion practices, and transfusion-related outcomes of MDS and CMML patients over a 15 year period, and explore whether access to disease-modifying therapies or the introduction of PBM guidelines impacted on transfusion requirements. Methods: Retrospective longitudinal cohort study including all patients with MDS/CMML admitted to hospitals in Victoria, Australia's second most populous state, from 2002-2017. Data linkage from the Victorian Admissions Episode Dataset (VAED) (contains data from all public and private hospital admissions in Victoria, including all transfusion episodes), the Victorian Cancer Registry and the Victorian Death Index was performed. We analysed transfusion episodes and outcome events (cardiac ischemia/failure, transfusion reactions, bleeding). Results: 6771 patients with a diagnosis of MDS/CMML reported to the Cancer Registry were included (5970 MDS; 801 CMML). The cohort was elderly (>50% aged 70y and over) and predominantly male (male 61%; female 39%). The majority of patients had a low number of comorbidities (Charlson Comorbidity Score: 60% low (0-2); 32% moderate (3-5); 8% high (≥6)). Of the 179 patients on 5-azacitidine, 38 (21.2%) commenced prior to 2011 and 141 (78.8%) from 2011 onwards. Patients on 5-azacitidine were more likely to be RBC transfusion dependent (TD) (defined as 2 or more RBC transfusions within 16 weeks) (77.7.1% vs 49.9%, p<0.001) and receive platelet transfusions (54.2% vs 28.6%, p<0.001). During the study period, the patients had a total of 142,765 hospital admissions. 66,068 (46.3%) admissions involved RBC transfusion, with median 3 admissions (IQR 1-10) per patient and median 14 days (IQR 14-33) between transfusions. 3433 (50.7%) of patients were RBC transfusion-dependent (TD). Comparing pre-and post-2011, the proportion of admissions involving RBC transfusion, median number of RBC transfusion admissions per patient, and rates of RBC-TD decreased (table 1). Cardiac events were common, and more frequent in RBC-TD patients (acute cardiac ischemia 14.6% vs 10.3%, p<0.001; acute cardiac failure 27.3% vs 14.1%,p<0.001). 10,049 (7.0%) admissions involved platelet transfusion. Platelet transfusion admissions increased over time (table 1). Median time between platelet transfusions was 7 days (IQR 4-16). 2436 patients (36.0%) experienced bleeding, including 51.3% of platelet-transfused patients. The commonest bleeding site was gastrointestinal (n=1388, 20.5%). Intracranial bleeding occurred in 175 patients (2.6%). 300 patients (4.4%) died from bleeding complications, with higher bleeding-related mortality in platelet-transfused patients (7.0% vs 3.4%, p<0.001) and RBC-TD patients (5.2% vs 4.0%, p=0.001). Conclusion: This study highlights the high transfusion burden in MDS patients, and related adverse cardiac and bleeding outcomes and mortality. RBC transfusion requirements reduced over time but platelet transfusions increased. This may be related to changing availability or use of MDS therapies, or clinical transfusion decision-making practices, or both - although national PBM guidelines do not specify a particular hemoglobin threshold for chronically transfused MDS patients, clinicians may be extrapolating from recommendations for restrictive transfusion thresholds in other settings (e.g. critical care, perioperative transfusion). These data will help design future MDS transfusion trials, which should include quality-of-life and health economics outcomes, given the burden of transfusion on these elderly patients. Figure 1 Figure 1. Disclosures Shortt: Amgen: Research Funding; Astex: Research Funding; BMS: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Wood: Amgen, Celgene, Gilead, Janssen, Novartis, Sanofi, Takeda: Research Funding; Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda.: Other: The Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) has received funding from Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda. .

Pro-Inflammatory Effects of Platelet Transfusions in Newborn Mice with and without Underlying Inflammation

Platelet transfusions (PTx) are frequently given to thrombocytopenic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding risk. However, in the largest randomized trial of neonatal PTx thresholds, infants transfused at a higher PC threshold had a significantly higher mortality and/or major bleeding compared to infants transfused at a lower threshold. Since platelets carry multiple cytokines and chemokines, and since activated adult platelets may have a higher ability to interact with immune cells than neonatal platelets (due to their higher P-selectin expression levels), we hypothesized that the deleterious effects of PTx in neonates would be related to pro-inflammatory effects. We further hypothesized that the effects of PTx on the systemic inflammatory response would be different in thrombocytopenic neonates with non-inflammatory conditions (e.g., intrauterine growth restriction, drugs, genetic syndromes) compared to neonates with underlying inflammation (e.g., sepsis, necrotizing enterocolitis). To test the effects of PTx in the absence of inflammation, we transfused healthy post-natal day 10 (P10) C57BL/6 pups with washed platelets (5x10 7/g, isolated from adult C57BL/6J mice or eGFP+ mice) or with Tyrode's buffer (TY control). Blood was collected via terminal bleed 2h, 4h, and 6h after transfusion, and plasma was separated for quantification of 31 pro- and anti-inflammatory cytokines by multiplex (n=5-10 mice per group/timepoint). Two hours after PTx, the transfused mice exhibited significantly higher levels of G-CSF, IL-1, IL-1, IL-6, IL-17, KC (CXCL1) and MCP-1 compared to controls, with the most striking increases observed in IL-6 (928±19 vs. 135±36 pg/dL, p<0.001) and KC (1201±239 vs 371±77 pg/dL, p=0.001). At 4h post-transfusion, the levels of most cytokines were decreasing, with the exception of G-CSF (1940±276 vs. 825±126 pg/dL, p=0.003), MCP-1 (185±39 vs. 58±14 pg/dL, p=0.003), and IL-17 (2.12±1 vs. 0.66±0.3 pg/dL, p=0.002), which peaked at four hours. All cytokines were decreasing by 6h. Next, to model neonates with inflammatory conditions, we injected P10 pups with lipopolysaccharide (LPS) IP at a sub-lethal dose (1µg/g), which induced mild weight loss, thrombocytopenia (~ 50% drop in PC), and leukopenia followed by leukocytosis. Two hours after LPS injection, pups were transfused with washed platelets from adult C57BL/6 mice or TY (as above). Blood was obtained by terminal phlebotomy 4h, 8h or 18h post LPS injection and plasma was separated and stored for cytokine quantification by multiplex. 4h after LPS, PTx pups had significantly higher levels of leukemia inhibitory factor (LIF, a member of the IL-6 family) compared to TY controls (35±6 pg/mL vs. 17±3.9 pg/mL, p<0.01). At both 4 and 8h, IL-6 and G-CSF levels were extremely high and at or above the upper limit of the standard curve in both groups. By 18h post-LPS, the majority of cytokines had decreased to near-normal levels in TY control pups, while IL-6, IL-5, KC (CXCL1) and IL-10 remained significantly elevated in PTx mice (IL-6: 601±114 vs. 187±38 pg/mL, p=0.0007; IL-5: 659±257 vs. 486±191 pg/mL, p=0.01; KC: 4569±1370 vs. 2686±827 pg/mL, p=0.04; IL-10: 729±283 vs. 330±131 pg/mL, p=0.009). Since IL-10 is an anti-inflammatory cytokine, we also evaluated the relation of IL-6 to IL-10 in PTx vs. TY control mice. This analysis showed that IL-6 levels were 2.3 times higher for any given IL-10 level in pups who received PTx compared to controls. In conclusion, our findings suggest that platelet transfusions induce an inflammatory response in newborn mice without underlying inflammation, characterized mostly by elevations in IL-6, G-CSF and KC. In newborn pups with underlying sub-lethal inflammation, platelet transfusions seem to prolong the inflammatory response. These observations may provide an explanation for the increased morbidity and mortality in human neonates receiving liberal PTx. Studies to identify the mechanisms through which platelets induce these responses are ongoing. Disclosures No relevant conflicts of interest to declare.

Use of an Antifibrinolytic Agent and Vitamin K As Alternative to Platelet Transfusions in Autologous Hematopoietic Cell Transplantation

Background Managing thrombocytopenia with a prophylactic strategy was previously recommended for patients with impaired bone marrow function, hematological malignancies, and recipients of HCT when platelet counts declined to under 10,000/uL. However, the updated 2018 ASCO guidelines now suggest a place for a therapeutic i.e., after a bleeding event rather than a prophylactic platelet transfusion strategy for patients with hematologic malignancies undergoing autologous HCT. Studies show a lack of significant difference between trial groups in hemostatic outcomes, such as the number of WHO grade 2-4 bleeds, and number of days with bleeding events. Platelet transfusions increase risks of infectious and non-infectious complications as well as inducing a platelet refractory state. Our Transfusion Free Medicine Program has now performed over 200 autologous hematopoietic stem cell transplants (HCT) in Jehovah's Witnesses who due to religious convictions, do not accept red cell or platelet transfusions. Vitamin K is a fat-soluble vitamin that is required for normal blood clotting. Autologous HCT patients are at risk for vitamin K deficiency from multiple reasons including malnutrition, frequent use of antibiotics, chemotherapy induced gastrointestinal toxicity leading to malabsorption and colitis. The prothrombin test lacks the sensitivity and specificity to detect mild deficiency. A mild vitamin K deficiency may be underdiagnosed in our transplant patients adding to bleeding risk. With the effective use of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions we believe this may enhance hemostasis and prove a valuable adjunct to a therapeutic approach. Methods Patients in our study were those who were of the Jehovah's Witness faith undergoing autologous HCT for Multiple Myeloma and Lymphoma. Patients received aminocaproic acid as an alternative to platelet transfusion to enhance hemostasis at a dose of 1 g every 4 hours or prophylactically for platelet counts less than 30,000 /uL. Titration to 4 g every 4 hours intravenously was required for platelet counts less than 10,000/ul or clinical bleeding. Vitamin K 10 mg orally or subcutaneous was also started at this time. Results Table 1 illustrates the low number of bleeding events especially grade 3 or 4 that occurred. There were no Grade 3 or 4 bleeding events in patients with platelet counts above 5000/uL. No patient had residual long term effects nor was there an increase in thromboembolic events. Conclusions These data add to the body of literature supporting a therapeutic platelet transfusion strategy in an experienced center for autologous HCT patients and challenges the prophylactic platelet count of 10,000 /uL suggesting instead 5000/uL. The safety and efficacy of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions to enhance hemostasis in autologous stem cell transplant patients may prove beneficial not only in JW patients but also in those transplant centers wishing to offer a therapeutic platelet transfusion approach and as a strategy to manage platelet refractoriness. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Aminocaproic Acid is an antifibrinolytic agent approved for treatment of bleeding in surgical patients and hematological bleeding disorders. Vitamin K is approved for use in reversal of anticoagulation from Warfarin, vitamin K deficiency without liver disease and in the newborn.