Transfusion Of Red Blood Cell Units Research Articles

Donor/recipient Rh-mismatched allogeneic hematopoietic stem cell transplantation: transfusion strategy and allo-immunization to red blood cell antigens.

In the case of donor/recipient rhesus (Rh)-incompatibility after allogeneic hematopoietic stem cell transplantation (alloHSCT), the transfusion policy in France is to transfuse red blood cells (RBC) in the donor's Rh phenotype from the day of transplantation, leading to a risk of allo-immunization, either of donor or recipient origin. In this single-center retrospective study, the incidence of donor/recipient Rh incompatibility was 7.1% over an 8-year period including 1012 alloHSCT. Six of 58 evaluable patients (10.3%) developed alloantibodies to RBC antigens within one year of alloHSCT. None of these allo-immunizations were directed against the donor-mismatched Rh antigens and none could have been prevented by the transfusion of recipient and donor Rh-compatible RBC units. None of these allo-immunizations led to immune-mediated hemolytic anemia. We observed a statistically significant higher incidence of chronic GVHD among patients with anti-RBC allo-immunization. In the context of donor/recipient Rh incompatibility, the transfusion of packed RBC units in the donor's Rh phenotype from the day of alloHSCT is feasible and not associated with a high risk of allo-immunization. The generalization of this strategy could be discussed even when donor and recipient Rh phenotypes could be respected, to allow the preservation of units of infrequent phenotypes for other indications.

Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC-transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012-2018. There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC-transfused patients had 1 (~46%) or 2-5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte-reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.

Impact of Patient Blood Management on Red Blood Cell Utilization in an Urban Community Teaching Hospital: A Seven-Year Retrospective Study.

This study aimed to showcase how implementing a patient blood management (PBM) program effectively cuts unnecessary red blood cell (RBC) transfusions in a New York City urban community teaching hospital. Analyzing seven years from 2013 to 2019, a retrospective review of RBC transfusions was conducted. Following the introduction of PBM, considerable improvements were observed annually. These included a drop in mean pretransfusion hemoglobin levels from 7.26 g/dL (2013) to 6.58 g/dL (2019), a 34% reduction in yearly RBC unit transfusions, and fewer units given to patients with pre-Hgb levels ≥ 7 g/dL (from 1210 units in 2013 to 310 units in 2019). Furthermore, this study noted a decline in two-unit RBC orders when Hgb levels were ≥ 7 g/dL from 65 orders in 2013 to merely 3 in 2019. The estimated total cost savings attributed to the six-year PBM program duration after full implementation in 2014 amounted to USD 2.1 million. Overall, PBM implementation significantly decreased RBC transfusions and enhanced transfusion practices. The findings emphasize that successful PBM strategies do not always necessitate extensive resources or increased budgets but instead rely on the application of intuitive methods, as evidenced by this study.

Obstetric blood transfusion in placenta previa patients with prenatal anemia: a retrospective study

BackgroundThe appropriate use of obstetric blood transfusion is crucial for patients with placenta previa and prenatal anemia. This retrospective study aims to explore the correlation between prenatal anemia and blood transfusion-related parameters in this population.MethodsWe retrieved the medical records of consecutive participants who were diagnosed with placenta previa and underwent cesarean section in our hospital. We compared the baseline demographics and clinical characteristics of patients with and without anemia. The correlation between prenatal anemia and obstetric blood transfusion-related parameters was evaluated using multivariate regression analysis.ResultsA total of 749 patients were enrolled, with a mean prenatal hemoglobin level of 10.87 ± 1.37 g/dL. Among them, 54.87% (391/749) were diagnosed with anemia. The rate of obstetric blood transfusion was significantly higher in the anemia group (79.54%) compared to the normal group (44.41%). The median allogeneic red blood cell transfusion volume in the anemia group was 4.00 U (IQR 2.00–6.00), while in the normal group, it was 0.00 U (IQR 0.00–4.00). The prenatal hemoglobin levels had a non-linear relationship with intraoperative allogeneic blood transfusion rate, massive blood transfusion rate, red blood cell transfusion units, and fresh plasma transfusion volume in patients with placenta previa, with a threshold of 12 g/dL.ConclusionsOur findings suggest that prenatal anemia is associated with a higher rate of blood transfusion-related parameters in women with placenta previa when the hemoglobin level is < 12 g/dL. These results highlight the importance of promoting prenatal care in placenta previa patients with a high requirement for blood transfusion.

Tired and stressed: direct holographic quasi-static stretching of aging echinocytes and discocytes in plasma using optical tweezers [Invited

Red blood cells (RBCs) undergo a progressive morphological transformation from smooth biconcave discocytes into rounder echinocytes with spicules on their surface during cold storage. The echinocytic morphology impacts RBCs' ability to flow through narrow sections of the circulation and therefore transfusion of RBC units with a high echinocytic content are thought to have a reduced efficiency. We use an optical tweezers-based technique where we directly trap and measure linear stiffness of RBCs under stress without the use of attached spherical probe particles or microfluidic flow to induce shear. We study RBC deformability with over 50 days of storage performing multiple stretches in blood plasma (serum with cold agglutinins removed to eliminate clotting). In particular, we find that discocytes and echinocytes do not show significant changes in linear stiffness in the small strain limit ( change in length) up to day 30 of the storage period, but do find differences between repeated stretches. By day 50 the linear stiffness of discocytes had increased to approximately that measured for echinocytes throughout the entire period of measurements. These changes in stiffness corresponded to recorded morphological changes in the discocytes as they underwent storage lesion. We believe our holographic trapping and direct measurement technique has applications to directly control and quantify forces that stretch other types of cells without the use of attached probes.

Preoperative Determination of Red Blood Cell Transfusion For Orthotopic Liver Transplantation in the Age of Artificial Intelligence

Abstract Orthotropic liver transplantation (OLT) is a major surgical procedure associated with significant blood loss. Unanticipated blood requirements during OLT can delay the procedure and compromise lifesaving intraoperative resuscitation, adding strains to the blood bank and blood suppliers' resources, especially when units are requested on short-notice or for patients with alloantibodies. Age, preoperative laboratory values, severity of underlying liver disease, and coagulopathy are factors that influence the number of units required. Currently, each transfusion medicine service issues a specific number of crossmatched red blood cell (RBC) units for OLT patients. At our institution, 10 crossmatched units are issued for each patient, which may be an overestimation or underestimation of the number of units required for certain patients. Aim: To characterize OLT patients who require more than 10 RBC units intraoperatively, and compare them to those who require less, identify pre-operative clinical and laboratory factors that predict which patients will require more than 10 units. Finally develop an artificial intelligence platform (AI-OLTRBC-1) aiming at reducing inappropriate RBC transfusions. Methods: We collected data from 485 patients that underwent OLT from January 1st, 2021 to December 31st 2022. Data collected included demographics, coagulopathies, anticoagulants, ABO/RH group, and laboratory testing collected within 24 hours of admission (complete blood count, prothrombin time (PT), partial thromboplastin time (PTT), INR, ALT, AST, total bilirubin, conjugated bilirubin, alkaline phosphatase (ALP), creatinine, Blood urea nitrogen (BUN), calcium and thromboelastogram (TEG). Data analysis was performed in R-studio (V.1.4.1). Missing values were imputated using multivariate imputation by chained equations algorithm. AI-OLTRBC-1 was built using machine intelligence learning optimizer platform. Results: Based on univariate regression analysis (p-value&amp;lt;0.05, 95% confidence interval) the following laboratory factors were found predictive of OLT patients requiring more than 10 RBC units: low albumin (OR 1.47 [CI 1.05-2.04]), increased total bilirubin (OR 1.06 [CI 1.041.08]), increased conjugated bilirubin (OR 1.08 [CI 1.04-1.11], increased creatinine (OR 1.55 [CI 1.33-1.83]), BUN (OR 1.03 [CI 1.02-1.04]), low hemoglobin (OR 1.61 [CI 1.81-1.42]), MCV (OR 1.04 [CI 1.02-1.07]), high INR (OR 3.48 [CI 2.35-5.26]), PTT (OR 1.04 [CI 1.03-1.06]), TEG-coagulation index (OR 1.12 [CI 1.05-1.19]). Among the anticoagulants, patients on enoxaparin required more RBC units (OR 1.47 [CI 1.66-11.1]). Other factors including demographic and ABO/Rh were not significant. The median number of transfused RBC units in patients requiring more than 10 units was 20, while the median number of transfused RBC units in patients requiring less was 5. Conclusions: Our study aimed to characterize OLT patients who required more than 10 units and identified preoperative factors to estimate RBC unit requirements, which would aid transfusion medicine service in providing RBC units properly and on-time. AI-OLTRBC-1 achieved a sensitivity of 88.0%, specificity of 70.4%, and an accuracy of 71.8% in classifying patients.

Time without Transfusion Reliance or Anemia Worsening: A Novel Method for Integrating Transfusion Dependence, Anemia, and Survival with Myelofibrosis Therapies Based on the Phase 3 Simplify-1 and Simplify-2 Trials

Introduction: While approved Janus kinase inhibitors (JAKi) have improved overall survival (OS) in myelofibrosis (MF), traditional survival analyses do not consider individual patient (pt) experience, which may be negatively impacted by factors such as persistent symptoms, adverse events (AEs), and red blood cell (RBC) transfusion dependence. In particular, RBC transfusions, an important component of anemia management in MF with currently approved JAKi, are associated with negative quality of life (QOL), increased healthcare resource utilization, and poor prognosis. Momelotinib (MMB), a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated consistent anemia benefits, including increased transfusion independence and reduced transfusion burden, as well as spleen and symptom improvements across 3 phase 3 trials in MF. In the SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) trials, achieving transfusion independence with MMB was associated with prolonged OS (Mesa R, et al. Leukemia. 2022). Here we apply time without transfusion reliance (TWiTR) analyses, integrating transfusion-dependent (TD) status and OS, to further characterize the benefits of MMB on survival quality. Methods: Analyses were performed in the safety populations, by treatment arm, over the randomized 24-wk treatment period of SIMPLIFY-1 (n/N=430/432; MMB vs ruxolitinib [RUX], JAKi naive) and SIMPLIFY-2 (N=156; MMB vs best available therapy [BAT; 88.5% RUX], JAKi experienced). TWiTR (Zeidner JF, et al. Haematologica. 2023) was based on the established time without symptoms and toxicity (TWiST) analysis, replacing toxicity with TD status. The analysis partitioned survival duration into 3 health states: (1) TD, defined as the number of days on which pts were TD (defined per protocol in the SIMPLIFY studies as requiring ≥4 units of RBC transfusions or having a hemoglobin level &amp;lt;8 g/dL in the previous 8 weeks) before experiencing a leukemia-free survival (LFS) event (leukemic transformation or death); (2) Post-LFS, defined as the number of days from an LFS event to death or censoring (OS; Post-LFS = OS − LFS); and (3) TWiTR, defined as the number of days without Post-LFS or TD (TWiTR = LFS − TD). An additional analysis incorporated the number of days on which pts had any-grade anemia events in the TD state (TD-Anemia [TD-An]) to define time without transfusion reliance or anemia worsening (TWiTR-An). Health state durations were estimated via Kaplan-Meier curves of the survival distribution function, with mean duration in each state calculated as the area under the curve. Results: In SIMPLIFY-1, pts in the MMB arm spent less time in the TD state and more time in the TWiTR state vs pts in the RUX arm (Figure 1). Mean duration in the TD state was 28.3 vs 62.7 days (difference with MMB, −34.4 days), while mean duration in the TWiTR state was 163.4 vs 131.1 days with MMB vs RUX (difference with MMB, 32.3 days). Fewer pts in the MMB arm had treatment-emergent anemia AEs, and incorporation of anemia events into the analysis increased the mean time spent in the TD-An state compared with the TD state in both treatment arms, although this increase was smaller in the MMB arm, at 32.0 vs 74.8 days in the RUX arm (difference with MMB, −42.8 days). Mean duration in the TWiTR-An state was 159.7 vs 119.0 days with MMB vs RUX (difference with MMB, 40.7 days). Similar results were observed in SIMPLIFY-2, although incorporating anemia events had less impact. Mean duration in the TD state was slightly shorter with MMB vs BAT, at 69.4 vs 89.9 days (difference with MMB, −20.5 days); mean duration in the TD-An state was 69.6 vs 89.9 days (difference with MMB, −20.3 days). Consistently, mean duration in the TWiTR state was slightly longer with MMB vs BAT, at 118.3 vs 95.9 days (difference with MMB, 22.4 days); mean duration in the TWiTR-An state was 118.0 vs 95.9 days (difference with MMB, 22.1 days). Conclusions: Pts treated with MMB spent less time reliant on RBC transfusions and more time free from transfusions and anemia events, without the cost of increased AEs, compared with those treated with RUX or BAT. Given the negative QOL and prognostic impact of RBC transfusion dependence, these analyses suggest that the anemia benefits of MMB lead to improved quality of survival for pts with MF.

Clinical Effectiveness and Safety of Momelotinib Compared with Continued Ruxolitinib or Best Available Therapy in Patients with Myelofibrosis Who Required RBC Transfusions: Subgroup Analysis of the Phase 3 Simplify-2 Study

Introduction: Splenomegaly, constitutional symptoms, and anemia are key clinical features of myelofibrosis (MF); approximately one-third of patients (pts) are anemic at diagnosis, and most develop anemia over time. While Janus kinase (JAK) inhibitors such as ruxolitinib (RUX) and fedratinib (FED) may address symptoms and splenomegaly, they do not manage and may exacerbate anemia. Treatments for anemia include erythropoiesis-stimulating agents (ESAs), often in combination with RUX or FED, and androgens such as danazol; however, these have shown limited efficacy. Red blood cell (RBC) transfusions are the mainstay of anemia management in MF, but transfusion dependency is associated with diminished quality of life and is a negative prognostic factor for survival. Treatments that address anemia as well as spleen volume and symptoms are needed. Momelotinib (MMB), a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated clinically meaningful and durable improvements in anemia, splenomegaly, and symptoms in pts with MF across 3 phase 3 trials. To evaluate outcomes in pts who switched to MMB vs continuing RUX or best available therapy (BAT) despite transfusion requirement, we present a descriptive subgroup analysis of pts enrolled in SIMPLIFY-2 (NCT02101268) who were considered transfusion dependent (TD; ≥4 units of RBC transfusions in the previous 8 wk or hemoglobin [Hb] level &amp;lt;8 g/dL) or transfusion requiring (TR; receiving transfusions but not meeting TD criteria) at baseline (BL). Methods: SIMPLIFY-2 was an international, multicenter, open-label, phase 3 clinical trial investigating the efficacy and safety of MMB vs BAT in pts with MF who had suboptimal responses or hematologic toxicities while receiving RUX. Pts (N=156) were randomized 2:1 to receive open-label MMB or BAT, which was RUX in 88.5% of pts. Treatment washout from prior RUX was not permitted before study enrollment. The primary endpoint was spleen volume reduction ≥35% (SVR35). Total Symptom Score (TSS) response rate (≥50% reduction; TSS50) and transfusion independence response (TI-R; no RBC transfusions for ≥12 wk immediately before the end of wk 24, with all Hb levels ≥8 g/dL) were key secondary endpoints. This post hoc, descriptive analysis focused on pts treated with either MMB or BAT, who were considered non-transfusion-independent (non-TI), defined as either TD or TR, at BL. Results: In SIMPLIFY-2, 72 of 104 pts (69%) in the MMB arm and 33 of 52 pts (63%) in the BAT arm were non-TI at BL, and BL characteristics were balanced between both patient groups. Mean duration of prior treatment with RUX was 64.6 and 59.5 wk in non-TI pts in the MMB and RUX arms, respectively. Average BL TSS for this subpopulation was 18.6. All pts randomized to the MMB arm received a starting dose of 200 mg daily. In the BAT arm, 29 of 33 pts (88%) were treated with RUX, with 59% receiving a BL dose of ≤20 mg daily. ESAs were administered to 5 pts in the BAT arm. At wk 24, SVR35 was observed in 7 of 72 pts (10%) treated with MMB and 1 of 33 pts (3%) treated with BAT. TSS50 was achieved in 21 of 72 pts (29%) treated with MMB, but there were no responses in the BAT arm. Additionally, TI-R was achieved in 25 of 72 pts (35%) treated with MMB compared with only 1 of 33 (3%) treated in the BAT arm on RUX. Many responders with MMB achieved 2 or all 3 endpoints (16 of 36 responders [44%]) (Figure); there were no dual or triple responses in the BAT arm. Of the 5 pts in the BAT arm who received ESAs, only 1 pt each (different pts per response) achieved SVR35, TSS50, or TI. Safety outcomes were consistent with those previously reported for the intent-to-treat (ITT) population. Conclusions: In RUX/BAT-treated pts with MF who required RBC transfusions, continued treatment with RUX/BAT in most pts resulted in poor treatment outcomes compared with MMB. Specifically, treatment with MMB demonstrated an ability to deliver higher SVR, TI, and TSS response rates. The lower SVR35 rate in both arms, similar to the overall ITT population, was likely a result of lack of washout from prior JAK inhibitor treatment. While pt numbers were limited, similar findings were observed compared with pts who received ESAs. Overall, these data support MMB as a potential alternative treatment option for pts with MF who require RBC transfusions. Figure. Responses at Week 24 for Non-TI Patients at Baseline

Longitudinal Assessment of Transfusion Intensity in Patients with JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated with Momelotinib in the Phase 3 Simplify-1 and Momentum Trials

Introduction: Anemia is a cardinal feature of myelofibrosis (MF), along with splenomegaly and constitutional symptoms. Red blood cell (RBC) transfusions, often used to manage anemia in patients (pts) with MF, are a negative prognostic factor for overall survival and are associated with diminished quality of life and increased healthcare-related economic burden. Momelotinib (MMB), a Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor, has demonstrated clinically meaningful and durable improvements in anemia, splenomegaly, and symptoms. Prespecified anemia endpoints in MMB phase 3 studies prioritized achievement of a strict transfusion independence response, defined as no transfusions for ≥12 wk immediately before the end of wk 24, with all hemoglobin levels ≥8 g/dL. Longitudinal analysis of transfusion intensity (units per 28 days) in a phase 2 trial of MMB in pts with transfusion-dependent MF demonstrated a reduction in transfusion burden in most (85%) pts (Harrison C, et al. EHA 2023). Here, we further characterize the impact of MMB and comparators on transfusion burden in pts with JAK inhibitor-naive and -experienced MF from the phase 3 SIMPLIFY-1 and MOMENTUM trials. Methods: This analysis evaluated time-dependent transfusion burden in pts enrolled in the phase 3 SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials. SIMPLIFY-1 included pts with JAK inhibitor-naive MF randomized (1:1) to receive MMB or ruxolitinib (RUX). In MOMENTUM, pts with symptomatic (Myelofibrosis Symptom Assessment Form Total Symptom Score ≥10), anemic (hemoglobin &amp;lt;10 g/dL), JAK inhibitor-experienced MF were randomized (2:1) to receive MMB or danazol (DAN). All RBC units transfused were collected during the 24-wk randomized treatment period of each study and during the 84 days before receipt of randomized treatment on study for baseline assessment. Time-dependent transfusion burden was quantified by number of RBC units administered, in a tabular display of baseline- and treatment-period intensity. Pts were grouped jointly based on the baseline- and treatment-period intensity of RBC units per 28 days into ordinal bins: exactly zero units, &amp;gt;0 to 1 unit, &amp;gt;1 to 2 units, &amp;gt;2 to 3 units, &amp;gt;3 to 4 units, and &amp;gt;4 units. Results: In SIMPLIFY-1 (JAK inhibitor-naive pts), 150 of 213 evaluable pts (70%) in the MMB arm and 163 of 216 evaluable pts (76%) in the RUX arm required zero units of RBC transfusion per 28 days at baseline. Of pts who required zero units of transfusion at baseline, a higher proportion in the MMB arm (142 of 150 [95%]) maintained a requirement of zero RBC transfusions during randomized treatment of 24 wks vs the RUX arm (93 of 163 [57%]). Overall, the mean RBC transfusion burden per 28 days declined 0.10 units (SD, 0.701) from baseline to randomized treatment in the MMB arm and increased 0.39 units (SD, 1.016) in the RUX arm. Using ordinal bins, 87% of pts in the MMB arm maintained (144 [67.6%]) or improved (41 [19.2%]) RBC transfusion intensity during randomized treatment compared with baseline vs 54% in the RUX arm (maintained, 94 [43.5%]; improved, 23 [10.6%]) (Figure). In MOMENTUM (JAK inhibitor-experienced pts), most pts had some transfusion requirement at baseline, with 26 of 130 (20%) in the MMB arm and 11 of 65 (17%) in the DAN arm requiring zero units of RBC transfusion per 28 days. During randomized treatment, a higher proportion of pts in the MMB arm (46 of 130 [35%]) required zero units of RBC transfusion vs the DAN arm (11 of 65 [17%]), including a higher proportion of those who had zero RBC transfusion requirement at baseline who maintained zero RBC transfusion requirement during randomized treatment (MMB, 92%; DAN, 64%). The mean RBC transfusion burden per 28 days declined 0.86 units (SD, 1.748) from baseline to randomized treatment in the MMB arm and declined 0.28 units (SD, 1.584) in the DAN arm. Using ordinal bins, 85% of pts in the MMB arm maintained (25 [19.2%]) or improved (85 [65.4%]) RBC transfusion intensity compared with baseline vs 63% in the DAN arm (maintained, 7 [10.8%]; improved, 34 [52.3%]). Conclusions: These data demonstrate that MMB was associated with better maintenance of RBC transfusion intensity and zero RBC transfusion status vs RUX in pts with MF who were JAK inhibitor naive and showed greater reduction in RBC transfusion burden from baseline vs DAN in pts with MF who were JAK inhibitor experienced. Across both trials, ≥85% of pts treated with MMB maintained or improved transfusion intensity.

High pre-transplant Mucosal Associated Invariant T Cell (MAIT) count predicts favorable course of myeloid aplasia.

Mucosal Associated Invariant T (MAIT) cells are unconventional T cells with anti-infective potential. MAIT cells detect and fight against microbes on mucosal surfaces and in peripheral tissues. Previous works suggested that MAIT cells survive exposure to cytotoxic drugs in these locations. We sought to determine if they maintain their anti-infective functions after myeloablative chemotherapy. We correlated the amount of MAIT cells (measured by flow cytometry) in the peripheral blood of 100 adult patients before the start of myeloablative conditioning plus autologous stem cell transplantation with the clinical and laboratory outcomes of aplasia. The amount of MAIT cells negatively correlated with peak C-reactive protein level and the amount of red blood cell transfusion units resulting in earlier discharge of patients with the highest amount of MAIT cells. This work suggests the anti-infectious potential of MAIT cells is maintained during myeloid aplasia.

Large volume acute normovolemic hemodilution in patients undergoing cardiac surgery with intermediate-high risk of transfusion: A randomized controlled trial

Study Objective: To investigate whether large volume acute normovolemic hemodilution (L-ANH), compared with moderate acute normovolemic hemodilution (M-ANH), can reduce perioperative allogeneic blood transfusion in patients with intermediate-high risk of transfusion during cardiac surgery with cardiopulmonary bypass (CPB).Design: Prospective randomized controlled trial.Setting: University hospital.Patients: Patients with transfusion risk understanding scoring tool (“TRUST”) ≥2 points undergoing cardiac surgery with CPB in the Second Affiliated Hospital of Zhejiang University from May 2020 to January 2021 were included.Interventions: The patients were randomly assigned with a 1:1 ratio to M-ANH (5 to 8 mL/kg) or L-ANH (12 to 15 mL/kg).Measurements: The primary outcome was perioperative red blood cell (RBC) transfusion units. The composite outcome included new-onset atrial fibrillation, pulmonary infection, cardiac surgery associated acute kidney injury (CSA-AKI) class ≥2, surgical incision infection, postoperative excessive bleeding, and resternotomy. Main results: Total 159 patients were screened and 110 (55 L-ANH and 55 M-ANH) were included for final analysis. Removed blood volume of L-ANH is significantly higher than M-ANH (886 ± 152 vs. 395 ± 86 mL, P < 0.001). Perioperative RBC transfusion was median 0 unit ([25th, 75th] percentiles: 0–4.4) in M-ANH group vs. 0 unit ([25th, 75th] percentiles: 0–2.0) in L-ANH group (P = 0.012) and L-ANH was associated with lower incidence of transfusion (23.6% vs. 41.8%, P = 0.042, rate difference: 0.182, 95% confidence interval [0.007–0.343]). The incidence of postoperative excessive bleeding was significantly lower in L-ANH vs. M-ANH (3.6% vs. 18.2%, P = 0.029, rate difference: 0.146, 95% confidence interval [0.027–0.270]) without significant difference for other second outcomes. The volume of ANH was inversely related to perioperative RBC transfusion units (Spearman r = −0.483, 95% confidence interval [−0.708 to −0.168], P = 0.003), and L-ANH in cardiac surgery was associated with a significantly reduced risk of perioperative RBC transfusion (odds ratio: 0.43, 95% confidence interval: 0.19–0.98, P = 0.044).Conclusions: Compared with M-ANH, L-ANH during cardiac surgery inclined to be associated with reduced perioperative RBC transfusion and the volume of RBC transfusion was inversely proportional to the volume of ANH. In addition, LANH during cardiac surgery was associated with a lower incidence of postoperative excessive bleeding.

Blood donor, component, and recipient-specific factors associated with venous thromboembolism in transfused hospitalized adult patients: Data from the recipient epidemiology and donor evaluation Study-III (REDS-III).

Growing evidence suggests multiple pathophysiological mechanisms linking red blood cells (RBC) transfusions to thrombosis. This study examined blood donor, component, and recipient factors which may be associated with thromboembolic outcomes following RBC transfusion. We utilized the Recipient Epidemiology Donor Evaluation Study-III (REDS-III) database on patients transfused in 12 hospitals between 2013-2016. Stratified Cox proportional hazards regression models with time-dependent exposures were used to examine associations of donor and component modification characteristics on venous thromboembolism (VTE) in patients transfused RBC units. 59,603 patients were transfused 229,500 RBC units during 79,298 hospitalizations with post-transfusion VTE occurring in 1869 (2.4%) of patients. In adjusted regression analyses, a per RBC-unit risk of VTE was present for gamma irradiation (HR=1.03; 95% CI: 1.02-1.03), female donor sex (HR=1.01; 95% CI: 1.00-1.01), storage duration greater than 5 weeks (HR=1.01; 95% CI: 1.01-1.02), AS-1 storage solution (HR=1.01; 95% CI: 1.00-1.01), and apheresis-derived collections (HR=1.01; 95% CI: 1.01-1.02). Among recipient factors, male sex (HR=1.03; 95% CI: 1.02-1.04), pre-transfusion hemoglobin level (HR=0.94; 95% CI: 0.94-0.94), body mass index strata (HR=1.11; 95% CI: 1.08-1.14), and principal diagnoses including malignancy (HR=1.13; 95% CI: 1.10-1.16), cardiac arrest (HR=1.38; 95% CI:1.07-1.77) and hip fracture (HR=1.59; 95% CI:1.53-1.66) were associated with VTE in adjusted analyses. We identified several donor, component, and recipient-specific factors associated with VTE in transfused hospitalized adult patients. In adjusted models, the dose-dependent associations of donor and component-specific factors with VTE were modest and unlikely to be clinically significant in the majority of transfused patients. Additional mechanistic and clinical studies linking blood donor and component factors with thrombotic outcomes are needed.

Influence of the grade and invasiveness of bladder cancer on disease course severity in patients with bladder tamponade resulting from a bleeding bladder cancer

Urinary bladder tamponade is a common urological emergency, but it has so far been insufficiently researched. The aim of our study was to show the association between the characteristics of bladder cancer (grade and invasiveness) and disease course severity based on blood hemoglobin (Hgb) count at admission, the need for red blood cell transfusion (RBCT), and the length of hospitalization in patients suffering from bladder tamponade. A retrospective, cross-sectional study was conducted, namely, including 25 adult patients surgically treated for bladder tamponade resulting from a bleeding bladder cancer. Patients with low-grade cancer had statistically significantly higher mean Hgb values at admission (101.14 ± 8.26 vs. 87.22 g/L ± 10.64 g/L, P = 0.005), as well as a lower mean number of received units of RBCT (0.71 ± 0.76 vs. 2.39 ± 1.46, P < 0.001) and a shorter hospitalization (2.43 ± 0.55 vs. 4.36 ± 1.04 days, P = 0.009) than those with high-grade cancer. Patients suffering from nonmuscle-invasive bladder cancer (NMIBC) had statistically significantly higher mean Hgb values at admission (96.69 ± 9.86 g/L vs. 81.22 ± 7.23 g/L, P = 0.001), as well as a lower mean number of received units of RBCT (1.31 ± 1.2 vs. 3 ± 1.41, P = 0.004) and a shorter hospitalization (3.31 ± 1.14 vs. 4.78 ± 0.97 days, P = 0.004) than those with muscle-invasive bladder cancer. Low-grade bladder cancer and NMIBC are associated with a milder clinical course of bladder tamponade.

RHCE variant alleles and risk of alloimmunization in Brazilians.

Variant RHCE alleles are found mainly in Afro-descendant individuals, as well as in patients with sickle cell disease (SCD). The most common variants are related to the RHCE*ce allele, which can generate partial e and c antigens. Although RHCE variant alleles have been extensively studied, defining their clinical significance is a difficult task. We evaluated the risk of RhCE alloimmunization as a consequence of partial antigens in patients with a positive phenotype transfused with red blood cell (RBC) units with the corresponding antigen. A retrospective study was performed with Brazilian patients, evaluating the number of antigen-positive transfused RBC units (incompatible due to partial antigen) in 27 patients with SCD carrying RHCE variant alleles who did not develop antibodies as well as evaluating the variants present in 12 patients with partial phenotype and correlated antibody (one patient with SCD and 11 patients with other pathologies). Two patients showed variant alleles with molecular changes that had not yet been described. Variant RHCE alleles were identified in a previous study using molecular methods. RHCE*ceVS.01 was the most frequent allele found among the patients without antibodies. Six patients with partial c antigen had a mean of 3.8 c+ RBC units transfused, and 10 patients with partial e antigen were exposed for a mean of 7.2 e+ RBC units. Among the variant alleles found in alloimmunized patients, the most frequent was RHCE*ceAR, which was found in five patients; the antibodies developed were anti-hrS and/or anti-c. Our results showed that RHCE*ceVS.01 is indeed the most frequent variant allele in our cohort of patients with SCD, but the partial antigens that were identified have low risk of alloimmunization. RHCE*ceAR is the most impactful variant in the Brazilian population with high risk of alloimmunization and clinically significant anti-hrS formation.

ASCENT1: A Phase 2 Trial to Evaluate the Efficacy and Safety of Oral Decitabine-Tetrahydrouridine (NDec) in Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is driven by the polymerization of mutated hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) mitigates the effects of HbS polymerization, but the HbF gene expression is silenced in infancy by DNA methyltransferase 1 (DNMT1). Decitabine induces HbF expression by direct inhibition of DNMT1. NDec is an innovative combination treatment with decitabine, the active component, and the pharmacokinetic enhancer tetrahydrouridine (THU). Hydroxyurea (HU), the current standard of SCD care, indirectly induces HbF by inducing bone marrow stress. As the indirect effect of HU on HbF is clinically variable, the direct HbF induction of NDec is hypothesized to provide a sustainable treatment option for patients with SCD. In a previous trial in high-risk patients with SCD by Molokie R et al. (2017), oral decitabine (0.16 mg/kg) and THU vs placebo significantly increased total Hb, HbF, proportion of HbF-enriched RBCs (%F-cells) and improved RBC health markers, without triggering grade ≥3 non-hematologic toxicity. NDec formulations were further investigated in 2 phase 1 trials in healthy people. The ASCENT1 trial (NCT05405114) aims to study the efficacy and safety of once- or twice-weekly NDec vs placebo in patients with SCD. This study will provide proof of concept and determine the optimal dose for future trials. Study design: ASCENT1 is a randomized, placebo-controlled phase 2 trial with an additional exploratory open-label HU block (Figure). To ease the operational aspects for patients and sites, trial design, visit schedule and trial materials were developed together with patient groups, study nurses and coordinators. The HU non-eligible block will include those who are HU-naïve or who cannot be treated with HU for any reason. Participants randomized to NDec in the HU active block will discontinue HU during a 4-week washout period. Study population: All SCD genotypes are eligible for inclusion; other criteria are ≥18 years of age, 2-10 documented vaso-occlusive crises (VOCs) ≤12 months before screening, Hb ≥5.0-≤10.5 g/dL and reticulocyte count >1.5x upper limit of normal at screening. HU active participants are eligible only if deemed inadequately controlled by investigators despite being prescribed HU in the preceding 6 months and being on a stable dose >3 months. Exclusion criteria include chronic transfusion therapy or treatment 28 days before screening/during trial with hematopoietic growth factors and treatment with voxelotor, crizanlizumab or L-glutamine 12 weeks before signing informed consent. Study treatment and endpoints: HU non-eligible (n=60) and HU active (n=24) participants will be randomized 1:1:1 to NDec once weekly, NDec twice weekly (2 consecutive days) or placebo/open-label HU. The trial consists of a main and extension phase (24 weeks each). NDec will be administered orally, with a meal, according to body weight intervals to attain a decitabine dose level of 0.16−0.25 mg/kg and THU dose level of 8−12.5 mg/kg. The primary endpoint is change in total Hb (g/dL) from baseline (BL) to Week 24. Secondary efficacy endpoints include change in HbF (g/dL and %HbF of total Hb), change in %F-cells of total RBCs, and change in hemolysis markers from BL to Week 24. Secondary efficacy endpoints also include numbers of VOCs, acute chest syndrome and transfused RBC units from BL to Week 48. The secondary safety endpoint is the number of adverse events (grade ≥3) from BL to Week 52. Changes in patient-reported outcomes from BL to Week 48 will be assessed using 5 validated questionnaires for SCD. Statistical analysis: The primary endpoint will be analyzed using an ANCOVA model with treatment, historical VOC rate and sex as fixed factors, and BL Hb as covariate. Treatment policy estimand will be used to handle intercurrent events. Considerations: In this trial, VOCs are defined as ≥1 predefined clinical events requiring a medical visit, including home and telemedicine visits, for those with limited regular access to medical management at a clinic/hospital. NDec and HU both induce HbF and will not be given together due to a theoretical potentiation of hematologic toxicity. The exploratory HU active block enables preliminary comparisons of the efficacy and safety between NDec and HU. The extension phase allows for analyses that may require longer follow-up to show clinical benefits and sustainability of NDec in SCD. The recruitment to ASCENT1 started in summer 2022. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Red Blood Cell Utilization Among Patients with Sickle Cell Disease: A Single Center Experience

Introduction: Red blood cell (RBC) transfusion remains a mainstay of treatment for both acute and chronic complications of sickle cell disease (SCD). RBC transfusions improve oxygen-carrying capacity of blood, decrease hemoglobin S levels, and are indicated for the treatment of complications such as stroke, acute chest syndrome, sickle cell hepatopathy and multiorgan failure syndrome. RBC transfusions may also be considered to reduce the frequency of pain crises for those intolerant or non-responsive to hydroxyurea. Prior practice surveys havedemonstrated significant practice variation in the management of patients with SCD with respect to RBC transfusions. The utilization of both simple RBC transfusions and red cell exchange (RCE) is poorly described, and unknown in the Canadian context, including at our center. The objective of this study is to describe RBC utilization at our center in a cohort of patients with SCD. Methods: All adult patients with SCD who have received care [inpatient, outpatient, or emergency department (ED)] at the Ottawa Hospital, from January 2006 to May 2019 were identified for study inclusion. Transfusion and health care utilization data was obtained through to December 2021 from clinical, administrative and laboratory databases at the Ottawa Hospital. Results: A total of 273 patients with SCD were identified. The median age for the cohort was 25 years (IQR 19,33) at first visit, with females comprising 53.9% of the cohort. The median duration of follow-up was 8.1 years (IQR 5,12.4). O-positive was the most frequent blood type (41.8%), and 8 (2.9%) individuals were O-negative. The annual RBC and health care utilization for the study cohort is depicted in Figure 1. The total number of hospital visits during the study period was 23127, with a median of 45 visits (IQR 18,100) per patient. 165 patients (60.4%) received 22538 RBC units with a median of 2 units (IQR 1,19) per patient, per year. 86.5% of the RBC units were infused in the outpatient setting, 12.1% in the inpatient setting and 0.8% in the ED. 40.3% of inpatient hospital visits were associated with an RBC transfusion event, compared to 2.4% of ED encounters. The proportion of RBC units transfused that were O-negative was 29.1% (6557 units). 147 patients received 2205 (9.7%) as simple RBC transfusions. The median number of simple RBC units transfused per patient, per year was 1 unit (IQR 1,2). 88 patients received 20333 RBC units during 2702 RCE sessions (median of 14.5 RCE sessions per patient), with 91.5% occurring in the outpatient setting. Of the 88 patients who received RCE, 64 patients (72.7%) had more than one RCE session, 54 patients (61.4%) had more than 5 RCE sessions and 48 patients (54.5%) had more than 10 RCE sessions. The median number of RBC units transfused per RCE session was 7 (IQR 6,9), with a median duration of 30 days (IQR 28,40) between RCE sessions. Conclusions: RBC transfusion was common in our cohort, with the majority of patients having received at least one RBC transfusion. The largest proportion of transfused RBC units stem from RCE use, which represents a small proportion of on our SCD cohort. O-negative units represented a large proportion of units transfused, despite the predominance of non-group O patients, likely due to both differences in donor and patient blood group phenotypes, and recommendations for extended phenotype matching. With pressure on transfusion medicine to provide appropriately matched units and the scarcity of O-negative units, further data accrual on RBC utilization, particularly assessment of indications, requirements for matching, and review of RCE procedures will define further quality improvement interventions to ensure optimal utilization of RBCs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-Dependent Anemia Due to Very Low, Low and Intermediate Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts, Who Had an Unsatisfactory Response to or Are Ineligible for Erythropoietin-Based Therapy: A Retrospective Multicenter Study By Fondazione Italiana Sindromi Mielodisplastiche (FiSiM ETS)

Background: Patients with lower-risk myelodysplastic syndromes (MDS) who develop red blood cells (RBC) transfusion-dependent anemia, experience worse quality of life and shorter survival. Therapeutic strategies after failure of erythropoiesis stimulating agents (ESAs) are limited. Regulatory approval of luspatercept in lower-risk MDS with ring sideroblasts (MDS-RS) offers a novel approach for the treatment of transfusion-dependent anemia in this subset of patients. However, data about luspatercept effectiveness in a real-world clinical setting are lacking. Here we report the results of a multicenter retrospective study including patients who were treated with luspatercept within the Italian compassionate use program. Methods: Eligible patients were ≥ 18 years old, had MDS-RS (2016 WHO classification), met criteria for very low, low, or intermediate IPSS-R risk; were receiving regular RBC transfusions (≥2 units/8 weeks in the 16 weeks before study entry); were refractory to or unlikely to respond to ESAs. Primary end point was transfusion independence (TI) for 8 weeks or longer during weeks 1 through 24; key secondary end point was TI for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. Other secondary end points included erythroid response (defined by the IWG 2006 criteria), progression to acute myeloid leukemia (AML) and safety analyses. Exploratory analyses were performed to identify predictive factors for treatment response. Results: 184 patients who were enrolled in the Italian luspatercept compassionate use program between December 2020 and December 2021 were analyzed in this study. Median age at enrollment was 74 years (range, 31-88), median time since diagnosis was 43 months, and median time since onset of transfusion-dependence was 23 months. Overall, 123 (66.8%) patients had at least one comorbidity requiring ongoing treatment, 39 (21.2%) had at least three. Baseline median transfusion burden was 6 RBC units every 8 weeks (range, 2-25). At the time of data analysis (June 30, 2022), 130 (73.4%) patients completed at least 24 weeks of treatment. Median time on treatment was 301.5 days, and median follow-up time was 376 days. During the first 24 weeks of the trial, 59 (32%) patients had TI for 8 weeks or longer. The percentage of patients achieving TI increased to 38.6% in the first 48 weeks of the trial. Median duration of TI was 27.9 weeks. Focusing on secondary endpoints, 36 patients (19.6%) had TI for 12 weeks or longer during the first 24 weeks, 52 (28.3%) had TI for 12 weeks or longer considering the first 48 weeks of the trial. A reduction ≥ 4 RBC units/8 weeks during weeks 1-24 was seen in 66 patients (40.2%). Four (2.2%) patients evolved to AML. Serious adverse events were recorded in 27 (15.2%) patients and led to study discontinuation in 5 (2.8%). Overall, treatment was discontinued in 72 (40.7%) patients, mainly for lack of benefit (table 1) The maximum approved dose (1.75 mg/kg) of luspatercept was administered at least once in 144 (81%) patients. Among patients who achieved TI for 8 weeks or longer in the first 48 weeks, luspatercept dose (mg/kg) at response was 1, 1.33 and 1.75 in 31 (46.3%), 18 (29.9%) and 18 (29.9%%) patients, respectively. Logistic regression analysis showed that higher baseline transfusion burden was significantly associated with a lower probability of achieving TI. We identified 3 group of patients stratified according to baseline transfusion burden (group 1, ≤4 units/8 weeks; group 2, 5 to 7 units/8 weeks, group 3, ≥8 units/8 weeks) with a significantly different probability to achieve both the primary endpoint (51.9%, 35.2% and 16.7%, respectively, P<0.01) and the key secondary endpoint (30.8%, 24.1% and 9%, respectively, P<0.01). Patients with higher transfusion burden had higher luspatercept doses at first response (table 2). In patients with low probability to achieve TI (group 2 and 3), a reduction in transfusions equal or greater than 4 units/8 weeks was achieved in 66 (46.2%). Conclusion: Luspatercept was effective for the treatment of transfusion-dependent anemia in MDS-RS in a real-life setting. The benefit extended beyond the achievement of TI and produced a significant reduction in the number of RBC transfusions. Higher baseline transfusion burden was associated with a reduced probability to achieve TI; in these patients, the reduction of transfused RBC units appears a more reliable treatment target. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Retrospective Review of Red Blood Cell Transfusion Practices in a Rural Community Hospital System

Introduction: Anemia is associated with increased length of stay and mortality in hospitalized patients. Red blood cell (RBC) transfusions could be lifesaving intervention and are generally used as a stabilizing measure until underlying etiology of anemia is identified and corrected. However, RBC transfusions have several adverse effects which occasionally could be life-threatening, including transfusion associated infections, immunologic reactions, volume overload, electrolyte imbalances, and iron overload. The decision on RBC transfusions should be based on patient's clinical status and physician's judgment, supported by data from randomized trials. Methods: In efforts to improve RBC transfusion practices in Northern Arizona Healthcare (NAH) facilities, all RBC transfusions between 01/01/2021 and 03/31/2022 were evaluated. Based on randomized clinical trial data, the following RBC transfusion thresholds were considered: Hemoglobin (Hgb) <8 g/dL for hospitalized anemic patients with established cardiovascular disease (CVD) or undergoing surgery, and Hgb <7 g/dL in hemodynamically stable hospitalized patients. Transfusions in pediatric patients, active/suspected blood loss, anemia with hemodynamic instability and massive or recurrent transfusions were excluded from the analysis. For the purpose of this study, RBC transfusion was deemed to be unjustified in cases where only 1 unit of RBC could have been sufficient to raise Hgb level above the specified threshold, however >1 unit was used with no clear justification. Results: A total of 2756 units of RBC transfusions were analyzed in hospitalized patients ages 18-102 years. Three patient groups were identified based on the documented provider justification for RBC transfusions: 1) Hgb <7 g/dL, 2) Hgb <8 g/dL with established CVD or undergoing surgery, 3) "other" who did not meet criteria for the previous groups. In the "other" group, the justification was manually entered by the provider. In the Hgb <7 group, 2004 RBC units were transfused in 1019 patients. Of those, 1440 units were transfused for Hgb level of 6.0-6.9 g/dL in 837 patients, with 273 patients receiving 2-4 units of RBCs when 1 unit could have been sufficient to raise the Hgb level >7 g/dL. Therefore, 303 RBC units were considered unjustified. Also, 83 units were deemed unjustified as they were transfused in 72 patients with pre-transfusion Hgb of ≥7.0 g/dL. In the Hgb <8 group, a total of 711 units were transfused in 500 patients. In the CVD group, 401 units were transfused in 287 patients, of which 260 patients had a Hgb of 7.0-7.9 g/dL. Thirty-four of these patients received 2-3 units when 1 unit was deemed sufficient to increase Hgb >8 (35 unjustified units). Additionally, 5 patients received at least 1 unit of RBC when Hgb was ≥8.0 g/dL (6 unjustified units). In patients undergoing surgery, 213 patients received 310 units. Of those, 150 patients had a Hgb 7.0-7.9 g/dL, 23 of which received >1 units (23 unjustified units). In the group classified as "other", 41 units were transfused in 39 patients. Hgb levels in this group were between 6.7 to 13.3 g/dL. After further evaluation, 18 units transfused in 17 patients were deemed to be unjustified. Discussion: RBC transfusion practices were evaluated in two hospitals in a rural setting in Arizona. From a total of 2756 units, 468 (16.9%) were deemed to be unjustified. The majority of these cases were seen in the Hgb <7 group. This is the first evaluation of RBC transfusion practices at this institution and a stepping stone to implement measures to improve these practices in the future. The next step includes creating an order set module that would not only require providing justification for blood transfusion, but also confirmation of pre-transfusion and desired target Hgb levels. Additionally, it would implement a notification encouraging single unit transfusions when feasible to decrease transfusion associated adverse reactions and cost burden on patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Outcomes of Ruxolitinib in Patients With Myelofibrosis Focusing on Red Blood Cell Transfusion: A Multicenter Study From the MPN Working Party of the Korean Society of Hematology

Ruxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF. We retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea. At ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence. The requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding.

Measurement of post-transfusion red blood cell survival kinetics in sickle cell disease and β-Thalassemia: A biotin label approach.

Red blood cell (RBC) transfusions are an important treatment modality for patients with sickle cell disease (SCD) and β-thalassemia. A subgroup of these patients relies on a chronic RBC transfusion regimen. Little is known about RBC survival (RCS) of the transfused allogeneic RBCs. In this study, we aimed to study the RCS kinetics of transfused RBCs in SCD and β-thalassemia and to investigate factors that determine RCS. We performed a prospective cohort study on fourteen adults with SCD and β-thalassemia disease receiving a chronic transfusion regimen. RCS and the influence of donor and patient characteristics on RCS were assessed by simultaneous transfusion of two allogeneic RBCs using RBC biotinylation. Phenotyping of well-known RBC markers over time was performed using flow cytometry. RCS of the two transfused RBC units was similar in most patients. Although intra-individual variation was small, inter-individual variation in RCS kinetics was observed. Most patients demonstrated a non-linear trend in RCS that was different from the observed linear RCS kinetics in healthy volunteers. After an initial slight increase in the proportion of biotinylated RBCs during the first 24 h, a rapid decrease within the first 10-12 days was followed by a slower clearance rate. These are the first data to demonstrate that patient-related factors largely determine post-transfusion RCS behavior of donor RBC in SCD and β-thalassemia, while donor factors exert a negligible effect. Further assessment and modeling of RCS kinetics and its determinants in SCD and β-thalassemia patients may ultimately improve transfusion therapy.