Number Of Platelet Transfusions Research Articles

Impact of restrictive platelet transfusion strategies on transfusion rates: A cohort study in very preterm infants.

Evidence supports a restrictive platelet transfusion threshold in preterm neonates. We aimed to describe the effect of implementing this threshold on transfusion rates. This retrospective observational cohort study included all very preterm infants (born <32 weeks' gestation) admitted to a neonatal intensive care unit between 2004 and 2022, divided into three epochs. Platelet transfusion thresholds changed from 30 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2004 to December 2009) to 20 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2010 to June 2019) to 25 × 109/L for non-bleeding neonates and 50 × 109/L for neonates with major bleeding (July 2019 to July 2022). The primary outcome was the percentage of transfused neonates in each epoch. Secondary outcomes included the median number of transfusions per neonate, the percentage of transfusions given above 25 or 50 × 109/L, and major bleeding and mortality rates. The percentage of neonates transfused was 12.2% (115/939), 5.8% (96/1660), and 4.8% (25/525) in Epoch I, II, and III, respectively (p < .001), a relative reduction of 61%. The median number of transfusions per transfused neonate was 2.0 (interquartile range [IQR]: 1.0-3.0) in Epoch I, and 1.0 (IQR: 1.0-2.0) in subsequent Epochs (p = .04). The percentage of infants receiving at least one transfusion above 50 × 109/L in Epoch I, II, and III was 51.3% (59/115), 17.7% (17/96), and 20.0% (5/25; p < .001). Mortality and bleeding rates did not significantly differ between epochs. Implementation of restrictive platelet guidelines led to reduction of the rate and number of platelet transfusions.

Assessing Donor and Platelet Transfusion Characteristics on Intracranial Hemorrhage Outcomes

Introduction: Intracranial hemorrhage (ICH) patients require rapid treatment to reverse coagulopathy, which can help establish hemorrhage control and improve outcomes. While acute platelet transfusions are given in ICH to reverse platelet dysfunction, delays in administration of hemorrhage control therapies and platelet unit characteristics themselves may impact the efficacy and clinical outcomes in different patient populations. Thus, we sought to evaluate the relationship of platelet transfusion timing and platelet unit characteristics with ICH mortality. Methods: Available data for incident hospitalizations of adult ICH patients between 2019-2022 from 3 of the 5 participating sites within the multicenter REDS-IV-P network were assessed. ICH patients were included if they received ≥ 1 acute platelet transfusion within 48 hours of admission and presented with one of the following ICH etiologies: trauma (tICH), spontaneous intracerebral hemorrhage (sICH), and aneurysmal subarachnoid hemorrhage (aSAH). Patients with early withdrawal of care and death within the first 48 hours were excluded. Separate logistic regression models (each adjusting for age, sex, race/ethnicity, comorbidities, and number of platelet transfusions) assessed the relationship of 30 day ICH mortality outcome with the following: a) time to initial platelet transfusion in hour quartiles: &amp;lt;2.7 hours [reference] vs 2.7-5.6 hours vs 5.7-14.5 hours vs 14.6-48 hours, b) any major ABO incompatible platelet transfusion versus identical or minor mismatch, and c) any donor-recipient sex mismatched platelet transfusion. Separate subgroup analyses were performed by ICH etiologic subgroups. Results: Amongst 619 ICH patients receiving an acute platelet transfusion, 52% were from tICH, 36% from sICH, and 12% from aSAH. Mortality was seen in 17% of the overall cohort. Longer times to platelet transfusion (longest quartile: 14.6-48 hours) were associated with mortality in the overall ICH cohort (adjusted OR 2.12; 95%CI: 1.10-4.12). In sICH, effect size estimates were notably greater with the longest quartile time to platelet transfusion also being associated with mortality (adjusted OR 4.66; 95%CI: 1.58-14.8). Longer times to platelet transfusion were not associated with mortality in tICH (adjusted OR 1.19; 95%CI: 0.45-3.15). Amongst 543 ICH patients with available donor-recipient ABO data, 32% received a major ABO incompatible platelet transfusion. While there was not an association of major ABO incompatible platelet transfusion with mortality in the overall cohort (adjusted OR 1.41; 95%CI 0.82-2.40), there again was a significant association of this exposure with mortality in the sICH subgroup (adjusted OR 3.06; 95%CI: 1.22-7.90). No associations of major ABO incompatible platelet transfusions were identified in tICH subgroup (adjusted OR 1.02; 95%CI: 0.49-2.10). We did not identify a relationship of sex mismatched platelet units with mortality in the overall ICH cohort or in any ICH subgroups. Conclusions: In our analyses of data available from the REDS-IV-P network, we identified a suggestive relationship between longer times to platelet transfusion and mortality, but not of ABO mismatch in our overall ICH cohort. However, sICH may be a specific ICH subgroup more vulnerable to platelet transfusion characteristics and practices, particularly time to platelet transfusion and major ABO incompatible platelet unit exposures. Further work is necessary to assess the generalizability of our data and to clarify whether certain adult ICH patients require specially tailored platelet transfusion approaches.

Toxicity Profile According to Etoposide and Cytarabine Dosing in Patients with Lymphoma Receiving Autologous Stem Cell Transplantation Following BEAM Conditioning.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is part of the treatment strategy for some patients with high-risk lymphoma by improving survival with an acceptable toxicity profile. Although the BEAM (BCNU, etoposide, cytarabine, and melphalan) intensification regimen is the most used, the optimal dosing for each drug is unclear. Here, we retrospectively compared the outcome of 110 patients receiving higher (400mg/m2, n = 69) or lower (200mg/m2, n = 41) etoposide and cytarabine doses in our institution between 2012 and 2019. Patients in the BEAM 200 group experienced less toxicity with reduced fever duration (P < 0.001), number of platelet transfusions (P = 0.008), antibiotic duration (P < 0.001), antifungal therapy (P < 0.001), and mucositis (P < 0.001) whereas length of stay, admission to the intensive care unit, and in-hospital mortality were not different between groups. Progression-free survival (PFS) was non-significantly lower in the BEAM 200 group (36-month PFS, 68% vs. 80%, P = 0.053) whereas OS was similar between the two groups (36-month OS, 87% vs. 91%, respectively, P = 0.12). Albeit a non-significant reduction in PFS, BEAM 200 conditioning intensity was associated with a reduced toxicity profile.

Open-label pilot study of romiplostim for thrombocytopenia after autologous hematopoietic cell transplantation.

There are no standard treatments to prevent or hasten the recovery from severe conditioning-regimen-induced thrombocytopenia occurring after autologous hematopoietic cell transplantation (auto-HCT). We conducted an open-label, single-arm pilot study of romiplostim, a thrombopoietin receptor agonist, to enhance platelet recovery in patients with multiple myeloma or lymphoma undergoing auto-HCT. All patients were treated weekly with romiplostim starting day+1 after auto-HCT until the platelet count was >50× 109/L without transfusion. Compared with contemporary retrospective data from romiplostim-naïve patients (N= 853), romiplostim-treated patients (N= 59) had a similar median number of days of grade 4 thrombocytopenia or days requiring transfusions, time to platelet engraftment, and number of platelets transfusions during the auto-HCT. However, romiplostim-treated patients had enhanced platelet recovery to normal values beginning at approximately day+15. In matched cohort multivariable analyses, romiplostim treatment was associated with higher platelet counts by an average of 40× 109/L (95% confidence interval (CI) (14, 67), P= .003) and 118× 109/L (95% CI [84, 152], P<.001) at days+21 and+30, respectively, compared with those of no romiplostim. Only 1 adverse event was deemed possibly attributable to romiplostim: a low-risk pulmonary embolism in a patient with multiple myeloma. In conclusion, romiplostim showed promising activity and safety after auto-HCT, but the improvement in platelet counts occurred later than the goal of shortening the duration and depth of the platelet nadir. This trial was registered at www.clinicaltrials.gov (#NCT04478123).

Is thrombocytopenia and postnatal weight gain associated with treatment-requiring retinopathy of prematurity? A matched case-control study.

The purpose of the study was to investigate the association of platelet parameters and postnatal weight gain with treatment-requiring ROP (TR-ROP). In this retrospective matched case-control study, infants with TR-ROP were individually matched, according to gestational age and birth weight, with one or two untreated infants who developed no or spontaneously regressed ROP. Longitudinal data on platelet count (PLT), mean platelet volume (MPV), daily weight and platelet transfusions were collected. Platelet mass index (PMI) and weight standard deviation score (WSDS) were also calculated. Conditional logistic regression analysis was performed to adjust for matching. Fourteen cases, presenting type I ROP, and 25 matched controls were included. The odds of developing TR-ROP decreased as PLT increased during 31st week of postmenstrual age (PMA) or during 1st and 2nd week of postnatal age (PNA). The odds of developing TR-ROP were 16.7 times higher in infants receiving at least one platelet transfusion compared with those who were not transfused. The odds of developing TR-ROP increased by 31.2% as the mean volume of platelet transfusion per infant increased by 1ml. The odds of developing TR-ROP decreased as PMI increased during 1st week PNA, and as weight and WSDS increased during 4th -6th week PNA. Analysis of MPV, number of thrombopenic episodes per infant, number of platelet transfusions per infant and days with WSDS < -2 showed no association with TR-ROP. To our knowledge, this is the first study ascertaining an association of platelet transfusions with type I ROP. Prospective cohort studies are required to confirm our findings.

241.5: Cryopreserved vs Non-cryopreserved Graft Before Autologous Stem Cell Transplantation in Patients With Multiple Myeloma. A Comparative Study

Introduction: Autologous Stem Cell Transplantation (ASCT) remains a standard first-line treatment in eligible patients with Multiple Myeloma (MM). Graft storage for a maximum of 72 hours at 2-6 C and infusion after high dose melphalan has been increasingly used and was adopted as an option for cryopreservation in our center in 2019. Objectives: To compare time to neutrophil engraftment (>500/ul), time to platelets engraftment (>20000/ul), days of hospital stay, engraftment failure, one-year overall survival (OS), one-year relapse-free survival (RFS), one-year relapse rate, 100-days transplant-related mortality (TRM), MM response at 100 days after transplantation, number of red blood cell transfusions, and number of platelets transfusions, between patients that received an ASCT with cryopreserved graft and those who received a graft stored at 2-6 C° (non-cryopreserved graft). Materials and Methods: We conducted a retrospective comparative analysis of MM patients’ clinical records that received an ASCT in our center from January 2019 to April 2021. Cryopreserved grafts were stored in freezer at -80 C, DMSO and albumin were added as institutional protocol. Non-cryopreserved grafts were stored at 2-6 C° for a maximum of 72 hours after collection. The conditioning regimen was melphalan 200/140 mg/m2 administered on day -2 with cryopreserved grafts and on day -1 with non-cryopreserved grafts. Kaplan-Meier curves were used for OS and RFS analysis and the long-Rank test was used for comparisons. The cumulative incidence function was used for TRM and relapse rate analysis. Results: From January 2019 to April 2021, 88 patients (median age 56,9 years) with MM received an ASCT in our center. 47 (53.4%) received a cryopreserved graft and 41 (46.6%) received a non-cryopreserved graft. No statistically significant difference was found between groups regarding age, sex, MM status before ASCT, number of treatments before ASCT, ISS stage, time to transplant, CD34+ dose, plerixafor use, and renal function. Conditioning regimen was melphalan 200 mg/m2 in 79 (89%) and 140 mg/m2 in 9 (11%) patients. The median time from collection to graft infusion in non-cryopreserved grafts was 45.5 hours. No statistically significant difference was found between groups with regard to time to neutrophil and platelets engraftment, number of red blood cell and platelets transfusions, OS, RFS, relapse rate, TRM, and MM response after transplant. There were no graft failure events. Patients receiving a non-cryopreserved graft had a shorter hospital stay (14 vs 15 days; p=0.008). Conclusion: ASCT with non-cryopreserved graft in MM patients showed similar results to the cryopreserved modality, with a shorter hospital stay and avoiding DMSO potential toxicity.

Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT‐ICU)

IntroductionThrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU.MethodsWe will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life‐support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90‐day mortality using logistic regression analyses.ConclusionThe outlined international PLOT‐ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

Management of cancer‐associated thrombosis with thrombocytopenia: Impact of the ISTH guidance statement

BackgroundOptimal management of cancer‐associated thrombosis (CAT) in patients with thrombocytopenia remains difficult given competing risks of recurrent thrombosis and increased bleeding. We determine the impact of the ISTH Scientific and Standardization Committee (SCC) guidance on CAT management and thrombocytopenia on platelet transfusion, bleeding, and recurrent thrombosis. MethodsA retrospective review was performed of patients with CAT and thrombocytopenia who required anticoagulation for VTE for 11 months before and after implementation of the ISTH SCC guidance. Medical records were reviewed to identify the type of VTE event, number of platelet transfusions, incidence of bleeding, and VTE recurrence within pre‐ and postintervention time periods. ResultsA total of 41 and 80 cases were included in the preintervention and postintervention periods, respectively. The preintervention group showed a trend toward less acute VTE events (39% vs 55%; P= .05). The postintervention period had an increased per‐patient platelet transfusion (median, 2.5 vs 4; P= .05). Nonmajor bleeding was increased in the postintervention group (2% vs 16%; P= 0.03) and included all six (8%) major hemorrhages (P= .09). There was numerically less recurrent thrombosis in the postintervention group (20% vs 8%; P= .07), which was not significantly different when accounting for acuity of VTE. Management adherence was strong, at 91%, in the postintervention group. ConclusionThe ISTH guidance on management of cancer‐associated thrombosis in patients with thrombocytopenia was successfully implemented in an academic medical center. There was no significant difference in bleeding or recurrent thrombosis outcomes after adjusting for acuity of VTE.

Optimizing Utilization of Blood Products in the Hematologic Malignancy Clinic: Less Is More.

There are no universal guidelines for blood product transfusions in patients with hematologic malignancies (HMs). Excess utilization of platelet and RBC transfusion in patients with HM increases the cost of care and likelihood of adverse events. We aim to decrease the total number of transfused units and multiunit orders of platelets and RBCs in the HM clinic by 25% from March 2020 to December 2020. A multidisciplinary, interprofessional team was formed. Baseline rates of blood product utilization were determined using Qlik Analytic software. Strategies to improve utilization were developed, and three interventions were initiated. Data were collected on monthly intervals. Data for total number of platelet and RBC units ordered, total multiunit orders, average number of units ordered per encounter, and pretransfusion hemoglobin thresholds were collected from May 2019 to December 2020. Through our Plan-Do-Study-Act cycles from March 2020 to December 2020, the total number of platelet transfusion orders per month decreased from 164 to 98, multiunit platelet orders decreased from 63 to 2, and the average number of platelet transfusions per encounter decreased from 1.62 to 1.03. The total number of RBC transfusion orders decreased from 172 to 141, multiunit RBC orders decreased from 25 to 16, and the average number of RBC transfusions per encounter decreased from 1.21 to 1.18. Implementation of our multidisciplinary interventions led to more appropriate use of blood products in the outpatient setting. Ongoing efforts are underway to continue to improve utilization in the inpatient and outpatient setting.

A Prospective Clinical Study of the Efficacy and Adverse Reactions of Azacitidine Combined with IA Regimen As the Induction Treatment of Newly Diagnosed AML

Objective:This single-arm prospective research (ChiCTR2100044731) aimed to evaluate the efficacy and safety of azacitidine combined with IA regimen in the induction treatment of newly diagnosed acute myeloid leukemia (AML), with a view to further improving the efficacy of acute myeloid leukemia with poor prognosis.Methods:Newly diagnosed AML (non-M3) patients who received azacitidine combined with IA regimen induction chemotherapy in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University from November 2019 to February 2021 were enrolled, and the efficacy and side effect were analyzed.Results: 1.A total of 33 patients were enrolled. The median age of the enrolled patients was 43.36 years (17-63), including 16 males (48.5%) and 17 females (51.5%). According to NCCN risk stratification, there were 3 patients (9.1%) in the favor group (9.1%) ,13 cases (39.4%) in the intermediate group and 17 cases (51.5%) in the poor group.2.The CR rate of one cycle of azacitidine combined with IA regimen was 66.7%, with a PR rate of 12.1% and a NR rate of 21.2%. After propensity score matching with the newly diagnosed AML patients who received IA regimen as induction chemotherapy in our center, a paired study was carried out. The results showed that there was no significant difference between the 2 groups in the treatment CR rate (66.7% for azacitidine combined with IA vs 54.5% for IA, P=0.592, Fig1). Subgroup analysis (table 1) showed combination of azacitidine with IA significantly improved the CR rate of patients with a ratio of blasts in the bone marrow greater than 67% (83.3% vs 30.8%, P=0.014) and patients in the intermediate NCCN risk group (100.0% vs 37.5%, P=0.001).3.The duration of agranulocytosis in the azacitidine combined with IA chemotherapy group was longer than that in the IA group (21 days vs 19 days, P=0.045). There was no significant difference in the number of platelet transfusions and the number of red blood cell transfusions between the two groups, and there was no significant difference in the incidence of infection between the two groups (table 2).Conclusions:The remission rate of induction chemotherapy for azacitidine combined with IA regimen and IA regimen in newly diagnosed non-M3 AML patients is comparable. Patients with a ratio of immature cells in bone marrow greater than 67% and patients in the intermediate NCCN risk group may benefit from azacitidine combined with the IA regimen. The combination of azacitidine with IA regimen aggravated granular bone marrow suppression. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Investigation of patient factors associated with the number of transfusions required during chemotherapy for high-risk neuroblastoma.

Blood transfusion is an important supportive care for high-risk neuroblastoma. When the number of transfusions increases, transfusion-associated adverse reactions may be more problematic. However, the factors determining the degree of myelosuppression and the number of transfusions during chemotherapy for high-risk neuroblastoma remain unclear. We investigated patient factors determining the number of required transfusions in 15 high-risk neuroblastoma patients who received five courses of chemotherapy. Clinical data, cytokine profile and colony-forming assay with bone marrow samples at diagnosis were analysed. The required number of transfusions of both platelets and erythrocytes decreased once in the second course and then increased as the course progressed. The variability among cases increased as the chemotherapy course progressed. In cases of low peripheral blood platelet count and lower fibrinogen level at diagnosis, the number of platelet transfusions was higher during chemotherapy. In contrast, there was a negative correlation between the forming ability of granulocyte-macrophage or erythroid colonies and the number of erythrocyte transfusions in the latter period. In the early stages of chemotherapy, bone marrow infiltration in neuroblastoma and/or coagulopathy complication may cause thrombocytopenia and requirement of platelet transfusion; conversely, in the later stages, the number of erythrocyte transfusions may be defined by the patient's inherent hematopoietic ability. These factors may be useful in predicting the required number of transfusions.

Economic Analysis of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Undergoing Remission Induction Chemotherapy from a Hospital Management Perspective

▪IntroductionInvasive fungal infections (IFI) are an important and trending causes of mortality in patients with acute leukemia. Especially during the remission induction, as well as stem cell transplantation, the patients bear the highest risk of IFI due to the prolonged severe neutropenia, long term exposure to broad spectrum antibiotics and cytotoxic chemotherapy.In a meta analysis of primary antifungal prophylaxis (PAT) in patients with malignancy receiving cytotoxic treatment and/or stem cell transplantation, antifungal prohylaxis was related with dramatic decrease in infection related mortality and decreased IFI. In another meta analysis focusing on prophylaxis with mould-active agents or fluconazole in hematologic malignancies has reported a significant decrease in IFI proven or probable, IFI related mortality and also with a concern, increased risk of adverse effects in the mould-active receiving group.Patients and Methods225 patients who have been diagnosed with acute myeloid leukemia (AML) and undergoing intensive treatment (idarubicin 12mg/m2 for three days and cytarabin 100mg/m2 24 h infusion for 7 days) for remission induction have been enrolled in the study in a retrospective manner. Direct health expenses like days of hospitalization, number of CT scans for thorax, development of complications, number of platelet apheresis infusions, mortality during remission induction treatment and total inpatient hospital costs. The benefits included cost reductions after adoption of primary antifungal prophylaxis.Results124 patients were male (55,4%) while 100 were female (44,6%). 90 patients received prophylactic treatment during remission induction therapy (40,2%). 43 patients died during remission induction therapy (19,2%). Mean number of thorax CT scans during remission induction was 1,73 (0-6). Mean number of days for hospitalization was 29,36 (14-88) days. Mean number of units of transfused thrombocyte apheresis was 9,9 (0-43) units. Mean cost of whole remission induction treatment was 9.151,6 (2.872,6-20.483,3) US dolars. Within patients who are not on PAT, 116 patients (86,5%) were treated with an intravenous antimould antifungal treatment while 5 of the patients on PAT (5,5%) received parenteral antimould antifungal treatment, 4 of which were related with neutropenic enterocolitis (p<0.005). 32 of the patients who are not on PAT died during remission induction (23,88%) while 11 of the patients who are on PAT died during remission induction (12,22%) (p=0.021). Mean days of hospitalization for remission induction treatment was 22,61 days for patients on PAT and 33,89 days for patients who are not on PAT (p<0.005). In patients on PAT, mean number of transfused platelet units was 6 (0-9) while 12,51 (4-43) units for patients who are not on PAT (p<0.005). When grouped as paients who are and who are not on PAT, there were significant difference between groups regarding total days of hospitalization, number of transfused platelet apheresis units, number of CT scans for thorax, death during remission induction and total cost of remission induction treatment in favor of patients on PAT. All significant data were analyzed with logistic regression analysis and observed as statistically significant. Results were summarized in Table.DiscussionIn Turkey, social security covers all the treatment for malignancies and complications, with rules and statements that lead the clinicians for decisions. Health Application Communiqué regulates the practice for reimbursement and since 2010, antimould antifungal agents are approved for prophylaxis in patients with AML who are undergoing remission induction therapy or patients undergoing hematopoietic stem cell transplantation. According to the physicians' or center's practices, PAT may be used and reimbursed.In our study, oral suspension form of posaconazole was effective to prevent IFI with a significant decrease in mortality during remission induction treatment. Likewise, PAT with posaconazole was observed to be cost-beneficial regarding the number of CT scans for thorax, number of platelet transfusion and over all costs of hospitalization for remission induction treatment. With its limitations regarding adherence as oral suspension form, tablet form may overcome these limitations. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Insulin-like growth factor-I predicts sinusoidal obstruction syndrome following pediatric hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT) initiated through damage of sinusoidal endothelium and inflammation. Insulin-like growth factor-l (IGF-l) maintains and repairs endothelium and intestinal mucosa. We hypothesized that low IGF-l levels may increase the risk of inflammatory complications, such as SOS, in HSCT-patients. We prospectively measured IGF-l concentrations in 121 pediatric patients before, during, and after allogeneic HSCT. Overall, IGF-l levels were significantly reduced compared with healthy sex- and age-matched children. IGF-I levels pre-HSCT and at day 0 were inversely associated with C-reactive protein levels, hyperbilirubinemia, and number of platelet transfusions within the first 21 days post-transplant. Low levels of IGF-I before conditioning and at day of transplant were associated with increased risk of SOS diagnosed by the modified Seattle criteria (pre-HSCT: OR = 1.7 (95% CI: 1.2-2.6, p = 0.01), and the pediatric EBMT criteria (pre-HSCT: 1.7 (1.2-2.5, p = 0.009) and day 0: 1.7 (1.3-2.5, p = 0.001)/SDS decrease in IGF-1). These data suggest that IGF-I is protective against cytotoxic damage and SOS, most likely through trophic effects on endothelial cells and anti-inflammatory properties, and may prove useful as a predictive biomarker of SOS.

The Comparison of Results of Autologous Transplantation Using Non-Cryopreserved and Cryopreserved Hematopoietic Stem Cells (HSC)

Background: Bone marrow (peripheral blood stem cells (PBSCs)) autologous transplantation is the standard care for transplant-eligible patients with multiple myeloma. This treatment option is somewhat limited due to the high consumption of economic resources and the access to Cryobank. We performed a retrospective analysis of multiple myeloma patients who underwent autologous transplantation using non-cryopreserved and сryopreserved grafts at our institution from March 2016 to April 2020. Aim: Compare the results of autologous transplantation using non-cryopreserved and cryopreserved hematopoietic stem cells (HSC). Methods: 78 patients with MM were included in the study (male/female ratio 1.3:1). All patients got the standard immunochemotherapy programs. They had remission (≥partial response) till the auto-HSCT. Patients were divided in two groups depending on the technique of HSC storage: non-CRYO (n=35) and CRYO (n=43). Cryopreservation is a standard method of storage of HSC suspension. In our work we used the native HSC suspension which was saved from +4 °C to +6 °C during 72 - 120 hours. An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, colony-forming ability (CFA). All of these were made after apheresis and before reinfusion of HSC. Also, we compared the duration of hematopoiesis's recovery, the number of platelet transfusions, the length of hospitalization after auto-HSCT. Additionally, the effectiveness of therapy was assessed according to the IMWG response criteria and the level of residual tumor load before SCT and on day +100. Results : There were no differences in the total number of CD34 + cells x 106/kg, or in the level of 7AAD- cells, or in the total CFA. However, there was a significant difference in the percentage of loss of CD34+ cells from the moment of apheresis to the moment of reinfusion. We suppose it was caused adverse effects by temperature changes in CRYO group. In both groups, there were no severe infusion reactions on day 0. The adverse events (nausea, vomiting, tachycardia, increased total bilirubin and indicator liver enzymes) were absent in the non-CRYO group. But 29/43 (67.4%) patients had such symptoms in the CRYO group on day 0. The results are presented in the comparison table (image 1) of the evaluated parameters. All patients had full recovery of hematopoiesis till discharge from the hospital. Neutrophil recovery was achieved at 11th day (range 9-14) and platelets at 12th day (range 8-19) in the non-CRYO group, and 10th day (range 8-14) and 12th day (range 8 -20) in the CRYO group, respectively. The frequency of achieving a partial response before autoHSCT was 37% (13/35), a very good partial response - 40% (14/35), a complete response - 23% (8/35) in the non-CRYO group and 72% (31/43), 14% (6/43) and 14% (6/43) in the CRIO group, respectively. HSCT was improved the efficiency of treatment as well as the frequency of complete and MRD-negative responses in both groups. Partial response after autoHSCT was achieved in 23% (8/35) patients, very good partial response in 40% (14/35), complete response in 37% (13/35) in the non-CRYO group compared to the CRYO group (47% (20/43), 21% (9/43) and 32% (14/43), respectively). The MRD status was assessed before and after autoHSCT in 48 patients. The frequency of MRD-negative response before autoHSCT was 8.7% (2/23), after transplantation - 21.7% (5/23) in the non-CRYO group and 4% (1/25) and 12% (3/25) in the CRYO group, respectively. AutoHSCT was increased the "depth" of the response in 25 patients. However, there were no significant differences between the same-type categories in the non-CRYO and CRYO groups (p&amp;gt;.05). AutoHSCT led to decrease of tumor load (TL). The average TL value was 0.55% before HSCT and 0.018% after HSCT (p=.036) in the non-CRYO group and 2.05 and 0.37 (p=.003) in the CRYO group, respectively. The mean TL after HSCT in the non-CRYO (0.018%) was smaller than mean TL in the CRYO (0.37%) groups (p &amp;lt;.05). Conclusion: The method of storage of PBSCs without cryopreserved is equal to traditional method controlled freezing with Dimethyl sulfoxide and can be used in hospitals which have no a Cryobank in their composition. Table Disclosures Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Lusutrombopag Is Safe and Efficacious for Treatment of Thrombocytopenia in Patients With and Without Hepatocellular Carcinoma

Patients with hepatocellular carcinoma (HCC) secondary to chronic liver disease often require invasive procedures but frequently have thrombocytopenia. Lusutrombopag is an agonist of the thrombopoietin receptor that activates platelet production. We performed an integrated analysis of data from 2 phase 3 trials (L-PLUS 1, Japan, October 2013 to May 2014, and L-PLUS 2, global, June 2015 to April 2017) that compared the efficacy and safety of lusutrombopag with placebo in patients with chronic liver disease, with and without HCC. Our analysis included patients with Eastern Cooperative Oncology Group grades of 0 or 1, Child-Pugh classes A or B, and a platelet count less than 50× 109/L who were scheduled to undergo invasive procedures in 9 to 14 days. Patients received lusutrombopag (3 mg) or placebo daily for 7 days or fewer before an invasive procedure. Imaging studies assessed treatment-emergent adverse events, including asymptomatic portal vein thrombosis. The primary end point was no requirement for platelet transfusion before the invasive procedure and rescue therapies for bleeding 7 days or fewer after the invasive procedure. The per-protocol population included 270 patients (95 with HCC). A significantly higher proportion of patients with HCC who received lusutrombopag achieved the primary end point (68.0%) vs patients who received placebo (8.9%) (P < .0001); in patients without HCC, these proportions were 77.0% vs 21.6% (P < .0001). Lusutrombopag reduced the need for platelet transfusions, increased platelet counts for 3 weeks, and reduced the number of bleeding events in patients with and without HCC compared with placebo. Risk of thrombosis was similar to that of placebo. Patients with and without HCC receiving lusutrombopag had a reduction in the number of platelet transfusions before invasive procedures compared with patients receiving placebo, with no increase in thrombosis or bleeding. L-PLUS 1: JapicCTI-132323; L-PLUS 2: ClinicalTrials.gov number no: NCT02389621.

Pre-Transplant Baseline Platelet Count and the Number of Peri-HSCT Transfusions Are Associated with an Increased Disease-Free Mortality Rate in a Large Pediatric Cohort

<h3>Introduction</h3> Platelets play a key role in the innate immune system as a source of pro-inflammatory cytokines. Lower platelet counts are associated with higher mortality in hospitalized adults with a variety of diseases, and platelet count <50,000 K/uL on arrival to the intensive care unit in recipients of allogeneic hematopoietic stem cell transplant (HSCT) is associated with decreased survival. Transfusion of platelets is common after HSCT for prevention and management of bleeding. <h3>Objective</h3> We hypothesized that platelet count prior to initiation of conditioning influences post-transplant outcomes, in part by increasing the need for platelet transfusions. <h3>Methods</h3> We retrospectively analyzed 388 patients undergoing first allogeneic HSCT at Cincinnati Children's. The last non-transfused platelet count at the time of admission for HSCT or start of conditioning regimen was considered the baseline platelet count (BPC). Patients transplanted for bone marrow failure syndromes were excluded due to underlying cytopenias. <h3>Results</h3> 35.8% of the cohort was transplanted for malignancy, 45.3% immunodeficiency, 11.6% hemoglobinopathies, and 6.7% genetic conditions. 114/388 patients in the cohort died (29%). Leading cause of death was acute graft-vs-host disease (aGVHD) followed by organ failure, primary disease, infection, and chronic GVHD (Fig 1a). BPC was significantly lower in deceased patients with no difference seen in baseline hemoglobin (Fig 1b). BPC correlated with the number of platelet transfusion by day +14 after HSCT, with a correlation coefficient of -0.49 (p < 0.001). BPC and the number of peri-transplant platelet transfusions were strongly associated with overall survival (OS) and non-relapse mortality (NRM), while baseline absolute neutrophil count (ANC) and conditioning regimen showed no association with OS (Fig 1c, d; Fig 2). Neither BPC nor the number of platelet transfusions influenced the risk for developing thrombotic microangiopathy (TMA) but lower BPC did increase the risk for developing moderate and especially severe GVHD (Fig 2). To investigate if low BPC is simply a marker for more ill and higher risk patient, we analyzed the subcohort of patients with a BPC in the normal range (> 135 K/uL). Lower BPC and the number of platelet transfusions were still associated with the risk for OS and NRM (Fig 3) <h3>Conclusion</h3> In a large cohort, lower BPC but not baseline hemoglobin or ANC are associated with more platelet transfusions and increased risk for NRM and worse OS. While platelet transfusions have previously been implicated in endothelial damage, this effect is independent of TMA risk. BPC is associated with the risk for GVHD, which is the leading cause of death in the cohort, although this appears independent of transfusion burden. Mechanistic studies are ongoing but these data suggest the need for thoughtful consideration of prophylactic platelet transfusion thresholds.

Thrombocytopenia and Anticoagulation: Impact of the ISTH SCC Anticoagulation Guidelines in Patients with Thrombocytopenia

Background Thrombosis is the second leading cause of death for cancer patients undergoing chemotherapy. Despite this, cancer patients also have a higher risk of clinically relevant bleeding related to thrombocytopenia secondary to chemotherapy or underlying disease. Optimal management of venous thromboembolism (VTE) in the setting of these competing risks is difficult. Generally, two strategies are used: (1) full dose anticoagulation with supportive platelet transfusions to maintain platelet count above 40,000-50,000/μL or (2) reduced-dose anticoagulation while platelets are &lt;50,000/μL. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (ISTH SCC) recently released updated guidance on management of anticoagulation in patients with cancer-associated thrombosis (CAT) and thrombocytopenia. We retrospectively reviewed cancer patients diagnosed with VTE and thrombocytopenia before and after implementation of the ISTH SCC guidance to determine the impact of the statement on platelet transfusion, bleeding, and recurrent thrombosis. Methods We evaluated cancer patients with thrombocytopenia who required anticoagulation for VTE for 11 months before and after implementation of the ISTH SCC guidance statement. Patients with malignancy, thrombocytopenia (platelets &lt;50,000), and administration of an anticoagulant were identified through an electronic medical search. Charts were retrospectively reviewed to identify the type of VTE event, number of platelet transfusions, incidence of bleeding, and VTE recurrence during thrombocytopenia within the pre- and post-intervention time periods. Cases were excluded if they were treated with anticoagulation for indications other than VTE. Summary statistics were calculated. Chi-square and Fisher's exact tests were used to compare categorical variables. Continuous variables were compared using the Mann-Whitney test. Results A total of 42 cases were identified in the pre-intervention time period and 82 cases in the post-intervention time period (Table 1). The median age was 62 years and the majority of patients (55% and 64%) were male. A total of 34 (80%) patients had experienced a PE or proximal DVT in the pre-intervention and 59 (72%) in the post-intervention time period (p=0.27). Significantly less patients experienced a VTE less than 30 days prior to thrombocytopenia in the pre-intervention compared to the post intervention time periods (33% vs. 55%, p=0.03). Likely secondary to this difference in acuity of the thrombosis, there was a trend to an increased per patient platelet transfusion in the post-intervention time period (median 2.5 vs. 4, p=0.05). Hemorrhage was noted in 2 (4%) of cases pre-intervention; and 14 (17%) in the post-intervention, only 4 (4%) of which were considered major hemorrhages by ISTH criteria (fatal bleeding and/or symptomatic bleeding into a critical area or organ, and/or bleeding causing a fall in hemoglobin of 2g/dL or more or that requires transfusion of two or more units of whole blood or red cells). A trend towards less recurrent thrombosis was noted in the post-intervention group (9% vs. 21%, p=0.07). Recurrent VTE events included 2 PE and 15 DVT. Adherence to the guidance statement was excellent (95% for medication management and 98% for platelet transfusions). Conclusion The ISTH guidance on management of cancer-associated thrombosis in patients with thrombocytopenia can be successfully implemented in an academic medical center. Trends towards higher incidence of bleeding and reduced incidence of thrombosis occurred. Disclosures Baumann Kreuziger: CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy.

Left Ventricular Assist Device (LVAD) Implantation Transiently Increases Plasma TGF-β1 in Heart Failure Patients: Potential Impact of Lvad on Platelet Activation

Although survival and quality of life have improved in patients with advanced heart failure (HF) after implantation of left ventricular assist devices (LVADs), they still pose risks of hemocompatibility-related complications, including thrombosis and bleeding. Development of biomarkers predictive of these LVAD-associated complications could guide decision making for both clinicians and patients. Recently, we showed higher plasma TGF-β1 levels within one-week after implantation with a miniaturized mechanical-bearing axial-flow pump HeartMate II (HM-II), and reasoned that platelet activation by the rotor may have caused the release of TGF-β1 in plasma in HF patients (Mancini et al. Transl. Res. 2018; 192:15-29). Recent clinical trials with the newest LVAD, the Heartmate 3 (HM-3), which uses a fully magnetically-levitated pump, showed superior clinical outcomes, including significantly reduced incidences of pump thrombosis and stroke (Mehra et al. N Engl J Med. 2019; 380:1618-1627). In this study, we evaluated release of TGF-β1 in plasma following implantation of HM-II and HM-3 LVADs compared to either coronary artery bypass graft (CABG) surgery or extracorporeal membrane oxygenation (ECMO) therapy. We measured serial total TGF-β1 levels in 38 Stage-D HF patients (11 received HM-II and 27 received HM-3). As a control, we collected blood samples from 10 patients undergoing CABG surgery, and 10 patients receiving ECMO therapy following acute onset cardio-pulmonary failure. Blood samples were collected before and 4-8 hours after procedures, and thereafter daily for up to one week. Plasma was prepared by centrifuging blood at 12,000 rpm for 5 min at 4°C within 10 min of blood drawing, which reduces in vitro release of TGF-β1 from platelets and thus allows accurate measurement of plasma TGF-β1. Total TGF-β1 levels were measured after acidification and neutralization of samples using DUO-ELISA kit (R&amp;D Systems). Baseline total plasma TGF-β1 levels were higher in HF patients before LVAD implantation than in healthy controls [4.7 ± 1.9 ng/mL in HF patients (n= 38); 3.3 ± 0.8 ng/mL in healthy controls (n= 6); p=0.006)]. Total TGF-β1 levels surged transiently to 14.6 ± 6.1 ng/mL within 4-8 hours after LVAD implantation [(p&amp;lt;0.0001 compared to patients 4-12 hours after CABG surgery (3.6 ± 1.4 ng/mL) or ECMO therapy (4.9 ± 1.3 ng/mL)]. Interestingly, however, we found that the transient surge of TGF-β1 in HM-3 recipients was significantly lower than in HM-II recipients (Figure-1; p=0.04). TGF-β1 levels then gradually decreased and reached near basal levels 2-3 days after LVAD implantation, but remained significantly elevated in plasma of HM-II recipients until day 5 (p=0.049). TGF-β1 levels remained unchanged in both CABG and ECMO patients at all time points (Figure 1). We conclude that LVAD implantation causes a transient surge in total plasma TGF-β1 within a few hours after the procedure, presumably due to platelet activation by LVAD, not the surgery itself, as CABG or circulating blood through ECMO did not cause the surge. The observation that a reduced initial surge and lower levels of TGF-β1 in HM-3 vs. HM-II recipients needs further investigation to determine whether these differences are due to LVAD-specific factors (different rotors causing variable shear effects) or to confounding differences in implantation procedures, such as, by-pass time, cardiac tissue injury, number of platelet transfusions, blood suction with catheters etc. or other unknown factors. Our data suggest that serial TGF-β1 measurements after LVAD implantation may serve as a surrogate biomarker for platelet activation in association with hemocompatibility-related adverse events (Uriel et al. Circ. 2017; 135:2003-2012). Disclosures No relevant conflicts of interest to declare.

Comparison of Outcomes after Early Hospital Discharge (EHD) Following Intensive Induction Vs. Post-Remission Chemotherapy for Adults with Acute Myeloid Leukemia (AML) and Other High-Grade Myeloid Neoplasms

Comparison of Outcomes after Early Hospital Discharge (EHD) Following Intensive Induction Vs. Post-Remission Chemotherapy for Adults with Acute Myeloid Leukemia (AML) and Other High-Grade Myeloid Neoplasms

03:00 PM Abstract No. 33 Evaluating blood product utilization and bleeding complications after implementation of single institution’s restrictive guidelines for periprocedural management of coagulation status in percutaneous image-guided interventions

Pre-procedure correction coagulopathy is of high priority in patients undergoing minimally invasive IR procedures. Unnecessary transfusion of blood products is associated with well-known infectious and non-infectious risks, however, uncorrected coagulopathy in the perioperative setting can be detrimental to the patient. Therefore, determining safe thresholds for administration of blood products is imperative, which in interventional radiology is mostly governed by the SIR consensus guidelines. The purpose of this study is to assess whether a single institution’s restrictive approach to pre-procedural transfusion of blood products can safely achieve outcomes similar to the established, more liberal guidelines. A total of 354 patients were enrolled in the study and a hypothetical comparison using Chi square method was made based on laboratory values that would have necessitated transfusion according to the SIR consensus guidelines (see table for transfusion cut-offs) Following our restrictive guidelines, high-risk group (n=119 patients), no FFP transfusion was required compared to 11 transfusions in the liberal group. Similarly, only 2 platelet transfusions were required in the restrictive group compared to 6 transfusions (p < 0.001) in the liberal group. In moderate-risk group (n=235 patients), there was statistically significant difference in the number of transfusions between the two strategies. Following our guidelines, only 1 FFP and 1 platelet transfusion were required compared to 26 FFP (p=0.004) and 7 platelet transfusions (p<0.003), respectively. Overall, in total of 354 patients, the number of FFP transfusion was only 1 in restrictive group compared to 37 in the liberal group (p = 0.003) and the number of platelet transfusion was only 3 compared to 13 in the liberal group (p<0.001). No difference in hemorrhagic complications was noted between patients receiving restrictive versus liberal transfusions. Restrictive transfusion strategy in patients undergoing IR procedures results in significant decrease in transfusions with no difference in hemorrhagic complications as well as drastic reduction in transfusion-related acquisition and activity-based costs.Tabled 1Transfusion Indications in Consensus GuidelinesTransfusion Indications in Restrictive Guidelines•Platelets ≤ 50,000•INR ≤ 1.5Non-cirrhotic Patients:•Platelets ≤ 30,000•INR ≤ 2.5Cirrhotic Patients:TIPS or Liver Biopsy = no•Platelets ≤ 30,000•INR ≤ 2.0TIPS or Liver Biopsy = YES•Platelets ≤ 50,000•INR ≤ 2.0 Open table in a new tab