Red Blood Cell Transfusion Requirements Research Articles

Thirty-Day Transfusion and G-CSF Requirement after CD19 CAR T Infusion

Introduction: CAR T therapy has improved overall survival for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who otherwise have poor outcomes with traditional chemoimmunotherapy. Cytokine release syndrome (CRS) and neurotoxicity are well known side effect from CAR T therapy. Cytopenia has been reported as well. However, to our knowledge, transfusion requirements during the first 30 days post-CAR T treatment have not been reported. Here we report the cytopenia characteristics and transfusion requirements in 15 patients who received commercial Axicabtagene ciloleucel (Yescarta) CAR-T cell therapy. Methods: We retrospectively reviewed all DLBCL patients who received Yescarta between July 2018 through May 2019 at Weill Cornell Medical Center. All patients received cyclophosphamide (500mg/m2) and fludarabine (30mg/m2) lymphodepleting regimen from days -5 to -3 before the CAR T cell infusion. Cytopenia, granulocyte-colony stimulating factor (G-CSF) use, packed red blood cell (RBC) and platelet transfusion requirements during 30 days after CAR T infusion were examined. Cytopenia was defined according to CTCAE criteria. Grade 3 cytopenia was white blood cell (WBC) <2 x 103/mL, absolute neutrophil count (ANC) <1 × 103/mL, hemoglobin (Hb )<8 g/dL or platelet count <50 × 103/mL. Grade 4 cytopenia was white blood cell (WBC) <1 x 103/mL, absolute neutrophil count (ANC) <0.5 × 103/mL, hemoglobin (Hb )<6.5 g/dL or platelet count <25 × 103/mL. Results: Median age was 68 years (range, 21-86yr) with 53% males (Table 1). Ten patients (67%) experienced cytokine release syndrome (CRS) with 8 patients receiving at least 1 dose of tocilizumab. Five patients (33%) experienced immune cell-associated neurologic syndrome (ICANS) and all received dexamethasone. Among patients with ICANS, one required ventilation support, one had a focal seizure and one had cerebellar ischemic stroke. Ten (70%) of the 14 evaluable patients had a D30 restaging PET/CT. Two patients had progressive disease and12 patients achieved partial response (PR). On admission, grade 3 or 4 leukopenia or neutropenia was observed in 0 patients, except 1 patient (WBC14.1, but ANC 0). There were 2 patients had grade 3 anemia, none of the patients had grade 4 anemia or grade 3/4 thrombocytopenia. Between D0 and D30, grade 3 or 4 leukopenia or neutropenia was observed in 12 patients (Figure 1). Grade 3 or 4 anemia was observed in 6 and 5 patients and grade 3 or 4 thrombocytopenia in 9 and 6 patients respectively. A total of 6 patients (43%) required G-CSF, 6 (43%) and 6 (43%) patients required red blood cell transfusion and/or platelet transfusion support. The median PRBC and platelet transfusion was 0 (range, 0-8) and 0 (range, 0-19). Three (20%) of the 15 patients accounted for the majority of the transfusion support. Conclusion: Cytopenia was common during the first 30 days after CAR-T cell therapy. Although nearly half of the patients required G-CSF and transfusion support, few patients had a significant burden. Disclosures Van Besien: Miltenyi Biotec: Research Funding.

Roxadustat (FG4592; ASP1517; AZD9941) in the Treatment of Anemia in Patients with Lower Risk Myelodysplastic Syndrome (LR-MDS) and Low Red Blood Cell (RBC) Transfusion Burden (LTB)

Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. Transient, intermittent HIF activation by roxadustat mimics a physiological response that increases endogenous erythropoietin (EPO) production to near physiologic range and stimulates EPO receptor synthesis. In addition, roxadustat promotes iron metabolism by reducing serum hepcidin to allow absorption of iron from the gut and mobilize iron from cellular storage making more iron available for erythropoiesis. Roxadustat corrected and maintained hemoglobin (Hb) in chronic kidney disease patients in multiple Phase 3 trials irrespective of underlying inflammation. In these studies, roxadustat-treated patients required less IV iron to correct and maintain Hb compared to erythropoiesis-stimulating agent (ESA)-treated patients. MDS is characterized by symptomatic anemia and many patients require RBC transfusion and/or ESA treatment. As response to ESAs varies across sub-populations with limited durability, there is an unmet need for treatment of anemia in LR-MDS. This is the first study to evaluate the effect of roxadustat in treating anemia in primary MDS patients. Methods: This is a two-part study; an open-label (OL), dose-finding segment (N=24) followed by a randomized double-blind (DB) placebo-controlled segment (N=156, 3:2 ratio of roxadustat to placebo). The primary goal of the OL segment is to identify the starting roxadustat dose-level for the DB segment. A total 24 patients in the OL segment have been enrolled in three sequential cohorts with 8 patients in each starting dose cohort (1.5, 2.0, or 2.5 mg/kg). RBC transfusion has been allowed per institutional criteria. Eligible patients were very low, low or intermediate risk primary MDS patients based on the International Prognostic Scoring System Revised classification with <5% bone marrow blasts; had baseline Hb < 10.0 g/dL; were >18 years old; and had LTB defined as receiving 1-4 RBC units per 8 week period. Patients were ineligible if they used an ESA within 8 weeks of the study start; had endogenous EPO levels >400 mIU/mL, or had a del(5q) cytogenetic abnormality. Roxadustat was administered TIW with doses titrated every 8 weeks per a dosing algorithm based on Hb response and transfusion need. Data from the OL segment were evaluated to identify the starting dose for the DB segment (currently enrolling). The primary endpoint is transfusion independence (TI) for ≥56 consecutive days during the first 28 weeks of treatment. The proportion of patients who achieve ≥50% reduction in RBC transfusion over any 8 weeks compared to baseline (8 weeks prior to Day 1) and proportion of patients who achieve TI for ≥20 consecutive weeks are evaluated. Safety and tolerability are assessed by adverse event reporting, percentage of patients progressing to acute myeloid leukemia (AML), and clinical laboratory values. Results: Twenty-four transfusion dependent, LR-MDS patients were enrolled in the OL segment of this global Phase 3 trial. Nine patients (38%) achieved TI for at least 56 consecutive days within the first 28 weeks.Three of 9 patients started at 1.5 mg/kg dose, 1 patient started at 2.0 mg/kg dose and 5 patients started at 2.5 mg/kg dose. At the time of achieving TI, 7 of 9 patients (78%) were on 2.5 mg/kg dose, 1 patient (11%) was on 2.0 mg/kg dose (started with 1.5 mg/kg dose) and one patient (11%) was on 1.5 mg/kg dose. Four patients remained TI for >20 weeks (one at 1.5 mg/kg dose level and three at 2.5 mg/Kg dose-level). One additional patient achieved TI after the initial 28-week dosing period at a dose-level of 3.5 mg/kg (starting dose 2.0 mg/kg). A total of 14 patients (58%) achieved a ≥50% reduction in RBC units in any 8-week period compared to baseline (range of 2-4 RBC units in 8 weeks before dosing); 12 of these patients were at ≥ 2.5 mg/kg dose level when achieving a 50% reduction in transfusion without need for IV iron. The overall safety profile observed is consistent with the patient population under study. Six patients reported 8 treatment-emergent SAEs with none being fatal. No patient has progressed to AML. Full results from the OL segment of the study will be presented. Conclusion: Based on the observed response (TI and transfusion reduction) and safety profile in LR-MDS patients, 2.5 mg/kg was selected as the starting dose for the ongoing 156-patient DB portion of the trial. Disclosures Harrup: Cooperative Trial Group for NeuroOncolog: Other: Collaborative Clinical Trials Group; Cancer Council of Tasmania: Membership on an entity's Board of Directors or advisory committees. Mittelman:Novartis: Honoraria, Research Funding, Speakers Bureau. Bradley:FibroGen Inc.: Employment, Equity Ownership. Saha:FibroGen Inc.: Employment, Equity Ownership. Bartels:FibroGen Inc.: Employment, Equity Ownership. Robert:FibroGen Inc.: Employment, Equity Ownership. Yu:FibroGen Inc.: Employment, Equity Ownership.

Results of a Clinical Trial of H3B-8800, a Splicing Modulator, in Patients with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML)

Results of a Clinical Trial of H3B-8800, a Splicing Modulator, in Patients with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML)

Clinical Efficacy of Ruxolitinib in Patients with Myelofibrosis: A Nationwide Population-Based Study in Korea

Background: The survival benefit of ruxolitinib, approved for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera (PV) MF, and post-essential thrombocythemia (ET) MF, has been reported in phase-3 studies. However, population-based comparison data of its efficacy in primary and secondary MF are limited. We analyzed the effects of ruxolitinib in MF patients from a real-world population using National Health Insurance Research Database of Korea. Methods: A total of 1171 patients who diagnosed MF (ICD-10 code D47.4) from January 1, 2011 to December 31, 2017 were identified. Of these, 291 patients previously diagnosed with leukemia, myelodysplastic syndromes, or lymphoma were excluded. The remaining 880 patients (361 patients with primary MF and 519 with secondary MF) were included in the study and divided into 2 group according to ruxolitinib treatment. Patients who received ruxolitinib (n = 276) were matched with those who did not receive ruxolitinib (n = 604) using the 1:1 greedy matching algorithm. Propensity scores were formulated using six variables: age, sex, previous history of arterial/venous thrombosis, red blood cell (RBC) or platelet (PLT) transfusion dependence, and previous hydroxyurea treatment. Overall survival (OS) and occurrence of acute leukemia and thrombotic complications were evaluated using stratified Cox-regression analysis between patients who received ruxolitinib and those who did not. Among the former, we evaluated the risk factors for OS as the primary outcome and occurrence of acute leukemia, thrombotic complications, and RBC and PLT transfusion response as secondary outcomes using multivariable Cox-regression analysis. Primary MF was defined as MF without a prior diagnosis of PV (ICD-10 code D45), ET (ICD-10 code D47.3), and chronic myeloproliferative disease (ICD-10 code D47.1). Secondary MF was defined as MF, which was not included in primary MF. Results: In the Cox-regression analysis for OS, non-ruxolitinib treatment (adjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.22-2.10; P <0.001) was a significant prognostic factor for shorter survival. In the subgroup analysis, non-ruxolitinib treatment was a significant prognostic factor for poor survival in patients with secondary MF (adjusted HR, 1.78; 95% CI, 1.28-2.48; P <0.001). Contrastingly, no significant difference was observed in patients with primary MF (adjusted HR, 1.00; 95% CI, 0.73-1.94; P = 0.478). Ruxolitinib treatment did not affect the occurrence of leukemia and thrombotic complications in patients with both primary and secondary MF. In the multivariable Cox-regression analysis for OS in patients treated with ruxolitinib, older age (adjusted HR, 1.06; P <0.001), RBC (adjusted HR, 2.91; P <0.001), and PLT (adjusted HR, 9.65; P <0.001) transfusion dependence were significantly associated with poor survival, although MF type did not significantly affect survival. In the multivariable analysis for secondary outcomes, PLT transfusion dependency was the only significant risk factor for the occurrence of acute leukemia (adjusted HR, 4.78; P = 0.046) and thrombotic complications (adjusted HR, 14.16; P = 0.002). Older age (adjusted HR, 1.05; P <0.001) and previous hydroxyurea treatment (adjusted HR, 0.41; P = 0.005) significantly affected the response to RBC transfusion. Patients with secondary MF who received ruxolitinib showed a better RBC transfusion response than those with primary MF (adjusted HR, 0.51; P = 0.055). Conclusions: Ruxolitinib treatment led to better survival in patients with MF and might be more beneficial in secondary MF. Moreover, ruxolitinib was more efficacious in reducing RBC transfusion requirement in secondary MF than in primary MF. Further studies on the efficacy of ruxolitinib in other populations are needed. Disclosures No relevant conflicts of interest to declare.

The Effect of Immigration on Adverse Perinatal Outcomes: Analysis of Experiences at a Turkish Tertiary Hospital.

Introduction In literature, it is well documented that migration is associated with adverse perinatal outcomes in many countries over the world. But in Turkey, health care providers and obstetricians had to face the effects of migration for the first time after civil war in Syria. Hence, this situation motivated us to conduct the current research in Turkey. Also we aimed to evaluate the effect of immigration on adverse perinatal outcomes, comparing the obstetric results of a native population and an immigrant population, and focusing on relevant indicators of perinatal health. Methods Information from the hospital database of pregnant women who had vaginal or cesarean delivery was evaluated. The patients were divided into two groups, native women and immigrant women, according to their ethnic origin. Adverse perinatal outcomes were compared between groups using multivariate regression models. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated. Results A total of 6311 patients were evaluated, of which 4271 were classified as native and 2040 were classified as immigrants. Mean hemoglobin level before delivery was significantly lower in the immigrant group. Preterm delivery (aOR: 1.41; 95% CI: 1.19–1.65), stillbirth (aOR: 1.88; 95% CI: 1.09–3.23), red blood cell transfusion requirement (aOR: 3.12; 95% CI: 2.02–3.98), unplanned birth rates before hospital arrival (aOR: 2.25; 95% CI: 1.53–3.31), and postpartum infection rates (aOR:2.12; 95% CI: 1.48–3.08) were significantly increased in the immigrant group compared with native group, even considering adjustment for potential confounders. Conclusion The immigration may be an important and independent risk factor for some adverse maternal and neonatal outcomes.

Blood utilisation and transfusion reactions in adult patients transfused with conventional or pathogen-reduced platelets.

SummaryPathogen‐reduced (PR) platelets are routinely used in many countries. Some studies reported changes in platelet and red blood cell (RBC) transfusion requirements in patients who received PR platelets when compared to conventional (CONV) platelets. Over a 28‐month period we retrospectively analysed platelet utilisation, RBC transfusion trends, and transfusion reaction rates data from all transfused adult patients transfused at the Yale‐New Haven Hospital, New Haven, CT, USA. We determined the number of RBC and platelet components administered between 2 and 24, 48, 72 or 96 h. A total of 3767 patients received 21 907 platelet components (CONV = 8912; PR = 12 995); 1,087 patients received only CONV platelets (1578 components) and 1,466 patients received only PR platelets (2604 components). The number of subsequently transfused platelet components was slightly higher following PR platelet components (P < 0·05); however, fewer RBCs were transfused following PR platelet administration (P < 0·05). The mean time‐to‐next platelet component transfusion was slightly shorter following PR platelet transfusion (P = 0·002). The rate of non‐septic transfusion reactions did not differ (all P > 0·05). Septic transfusion reactions (N = 5) were seen only after CONV platelet transfusions (P = 0·011). These results provide evidence for comparable clinical efficacy of PR and CONV platelets. PR platelets eliminated septic transfusion reactions without increased risk of other types of transfusions with only slight increase in platelet utilisation.

Thalidomide Use Reduces Risk of Refractory Gastrointestinal Bleeding in Patients with Continuous Flow Left Ventricular Assist Devices.

Gastrointestinal (GI) bleeding is a common complication seen in patients with implanted continuous flow left ventricular assist devices (CF-LVAD), often attributed to arteriovenous malformations (AVMs). Whether thalidomide reduces recurrent GI bleeding risk in CF-LVAD patients has been incompletely evaluated. We conducted a retrospective review of all CF-LVAD patients at our institution with GI bleeding from AVMs who had a trial both off and on thalidomide. The primary endpoint was time to rebleed, while secondary endpoints included overall GI bleeding events, packed red blood cell (PRBC) transfusion requirements, and adverse events related to thalidomide. We report on 24 patients with recurrent AVM-associated GI bleeding who met criteria for and received thalidomide therapy, of which 17 had sufficient follow-up to be ultimately included for final analysis. We found the risk of rebleeding was significantly reduced in those on thalidomide therapy versus off (hazard ratio = 0.23, p = 0.022). The median number of GI bleeds per year was reduced from 4.6 to 0.4 (p = 0.0008) and the PRBC requirement was lower (36.1 vs. 0.9 units per year, p = 0.004) in those on thalidomide therapy. The adverse event rate with thalidomide was 59%, with symptoms resolution in most following dose reduction without increased bleeding. Thalidomide reduced the risk of AVM-associated GI rebleeding, number of bleeding events, and PRBC requirements in CF-LVAD patients. When initiating therapy, potential side effects and overall clinical context should be considered.

A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759).

Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.

The Comparison of The Efficacy and Safety of Original and Biosimilar Filgrastim in Prevention of Chemotherapy-Induced Neutropenia in Children with Cancer.

In adults and children, the duration of chemotherapy-induced neutropenia and associated complications has decreased because of the prophylactic use of granulocyte colony-stimulating factors (G-CSFs). Biosimilar G-CSFs can play an important role in reducing treatment costs in daily practice. However, some concerns regarding the efficacy and safety of new biosimilar products exist among clinicians. This study compared the efficacy and safety of original and biosimilar filgrastims for the prophylaxis of chemotherapy-induced neutropenia in children. Thirty children receiving myelosuppressive chemotherapy were enrolled in this study. Filgrastims (5 μg/kg/day) were subcutaneously administered in Group A (biosimilar, Leucostim®; Dem İlaç) and Group B (original drug, Neupogen®; Roche). Hemoglobin, white blood cell (WBC) count, platelet count, transfusion requirements, duration of hospitalization, and frequency and duration of adverse events including fever, neutropenia, and mucositis were evaluated following 25 treatment cycles in both groups. The hemoglobin value, WBC count, and platelet count on days 1, 5, and 10, and the red blood cell and platelet transfusion requirements, frequency, duration, and severity of mucositis, and durations of fever, febrile neutropenia, and hospitalization were similar in both groups. Although the mean WBC counts on days 1 and 5 were lower in Group A, the difference was statistically insignificant. The biosimilar filgrastim, Leucostim, is as effective and safe as the original drug for prophylaxis of chemotherapy-induced neutropenia in children.

Hematologic improvement with iron chelation therapy in myelodysplastic syndromes: Clinical data, potential mechanisms, and outstanding questions.

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenias and progression to acute myeloid leukemia (AML). Although several treatments for MDS are available, the mainstay of therapy for most patients remains supportive care. This includes red blood cell (RBC) transfusion to correct anemia, which leads to iron overload. RBC transfusion dependence and iron overload portend inferior overall survival. Some studies indicate that iron chelation therapy (ICT) may have beneficial effects on clinical endpoints in MDS; however, these data are from non-randomized trials and the validity of the results is vigorously debated. A consistent observation in clinical studies of ICT in MDS has been hematologic improvement (HI) in some patients, including a reduction in RBC transfusion requirements and even transfusion independence. Here, we review data on HI with ICT in lower risk MDS, preclinical data examining mechanisms by which HI may occur, and identify areas for future investigation.

Increased Transfusion Requirements with Pharmacologic Thromboembolism Prophylaxis During Inflammatory Bowel Disease Exacerbation.

Inflammatory bowel disease (IBD) exacerbation requiring hospitalization increases the risk of venous thromboembolism (VTE), and current guidelines recommend pharmacologic VTE prophylaxis (PVTEP). Bleeding risks with PVTEP in this population are poorly defined, and no study has investigated packed red blood cell (PRBC) transfusion requirements in this population. We conducted a chart review of all adult hospitalizations for IBD exacerbation within the Northwell Healthcare system. Patient characteristics recorded included demographics, disease type ulcerative colitis or Crohn's disease, severe disease defined by inpatient corticosteroid or biologic use, and admission hemoglobin. Inpatient use of PVTEP and anti-platelet therapies were identified. The primary outcome was the occurrence of any packed red blood cell (PRBC) transfusion. In total, 717 patients met inclusion criteria, accounting for 891 admissions. PVTEP was used during 60.4% of admissions, and 11.1% of patient admissions included a transfusion event. Severe disease patients receiving PVTEP had an 18.6% transfusion risk, versus 11.1% for those not receiving PVTEP, OR 1.82, CI (1.04-3.17). One multivariable analysis transfusion was associated with PVTEP, OR 2.11, 95% CI 1.18, 3.77, p = 0.0120, disease severity OR 3.17, 95% CI 1.81,5.54, p < 0.0001, anti-platelet therapies OR 2.46, 95% CI 1.23-4.90, p = 0.0107, bowel resection OR 3.88, 95% CI 1.97,7.63, p < 0.0001 and decreased admission hemoglobin OR 2.01, 95% CI 1.73-2.32, p < 0.0001, but not disease type ulcerative colitis OR 0.71, 95% CI 0.42-1.20. PVTEP during IBD exacerbation is associated with increased PRBC transfusions. Our findings do not constitute a contraindication to PVTEP, but may be incorporated into patient counseling during inpatient IBD management.

Issue Highlights - May 2019.

Issue Highlights - May 2019.

Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions.

Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusions but alloimmunization remains a significant complication. Alloantibodies can lead to delayed hemolytic transfusion reactions (DHTRs) days to weeks after a RBC transfusion, but may be underrecognized in patients with chronic hemolysis. This retrospective study aimed to determine the incidence and severity of DHTRs associated with new antibody detection in a cohort of 624 patients with SCD who received transfusion with C-, E-, and K-matched RBCs from primarily African American donors over a 14-year period. We identified potential DHTRs by the change in hemoglobin (Hb) and %HbS at baseline, before transfusion, and up to 30 days after the transfusion that preceded new antibody identification. Laboratory evidence of a DHTR was associated with 54 of 178 evaluable antibodies at first detection (30%), among which less than half were recognized by the patient or provider at the time of the event. A DHTR was associated with 26% of Rh antibodies identified in patients receiving serologic Rh-matched RBCs, and 38% of non-Rh antibodies. Twenty-one of the 54 DHTRs (39%) were associated with a Hb decline greater than 1 g/dL lower than pretransfusion values. Among these 21 severe DHTRs, Rh specificities were identified in 10 of 12 DHTRs in chronically transfused patients, while non-Rh specificities were associated with seven of nine DHTRs in episodically transfused patients. High clinical suspicion and monitoring for DHTRs is warranted, as they may be more common in patients with SCD than previously appreciated.

RISK FACTORS FOR BLOOD TRANSFUSION IN WOMEN UNDERGOING GYNAECOLOGICAL SURGERY

Objectives A common complication of surgery is peri-operative blood loss, which increases the likelihood of red blood cell (RBC) transfusion and its associated risks. The objective of this study was to identify demographic, medical, and surgical factors that may predict the need for RBC transfusion in patients undergoing benign gynaecological surgery. Methods We performed a retrospective cohort study of patients undergoing benign gynaecological surgery between April 1st 2016 to March 31st 2017 in a tertiary care hospital. Log binomial regression model was used to calculate risk ratios and adjusted risk ratios, while controlling for the effect of preoperative anaemia. Results Among the 988 patients included, 41 patients (4.1%) received an RBC transfusion and 185 (18.7%) had preoperative anemia. In the total cohort, mean haemoglobin was 126.19+/-15.43g/L, while itwas 104.39+/-21.59g/L among those who received RBC transfusion. Patients had an increased risk of requiring RBC transfusion if they had preoperative anemia (RR 8.37[95%CI 4.48-15.64]), abnormal uterine or vaginal bleeding (RR 2.47[95%CI 1.21-5.03]), underwent vaginal/hysteroscopic myomectomy (RR 6.28[95%CI 1.82-21.69]), or had a salpingectomy (RR 2.13[95%CI 1.01-4.48]). Risk of RBC transfusion was lower among patients with vaginal hysterectomy (RR 0.08[95%CI 0.01-0.57]) and prolapse repair (RR 0.06[95%CI 0.01-0.44]). After controlling for preoperative anemia, only vaginal/hysteroscopic myomectomy showed increased risk of requiring RBC transfusion (RR 3.36[95%CI 1.13-10.01]). Conclusions Preoperative anemia and vaginal/hysteroscopic myomectomy are important independent risk factors for predicting the need for increased RBC transfusion in the peri-operative period. Identifying risk factors can facilitate peri-operative management to minimize the need for transfusion.

Thalidomide Use Reduces Risk of Refractory Gastrointestinal Bleeding in Patients with Continuous Flow Left Ventricular Assist Devices

Methods We conducted a single-center, retrospective review of all CF-LVAD patients at our institution who subsequently experienced GI bleeding events, underwent endoscopy, and were treated with thalidomide. Only patients who had bleeding from suspected or confirmed AVMs and had a trial both off and on thalidomide were included. Our primary endpoint was reduction in time to re-bleed, while secondary endpoints included reduction in number of GI bleeding events, reduction in packed red blood cell (PRBC) transfusion requirements, and adverse events related to thalidomide. Results Of the 274 CF-LVAD patients at our institution, 11.3% had recurrent GI bleeding, of which 17 were treated with thalidomide and had a sufficient observation period prior to and during treatment. The risk of re-bleeding was significantly reduced in patients on thalidomide therapy versus off (hazard ratio = 0.23, p = 0.022). The median rate of GI bleeding events was reduced from 4.6 to 0.4 events per year (p = 0.0008) and the median PRBC requirement was lower (36.1 vs 0.9 units per year, p = 0.004) in those on thalidomide therapy. While side effects, including dizziness and peripheral neuropathy, were seen in approximately 59% of patients on thalidomide, most resolved with dose reduction without any increase in bleeding, and only 11% required discontinuation. Conclusion Among patients with CF-LVAD implantation who subsequently experience recurrent GI bleeding related to AVMs, treatment with thalidomide markedly reduced the GI re-bleeding risk, number of recurrent bleeding events and PRBC transfusion requirement. Our findings suggest that thalidomide should be considered as a medical therapy for the treatment of recurrent GI bleeding in CF-LVAD patients.

Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients.

Relationships between red blood cell (RBC) transfusion, circulating cell-free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients. This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion. Cell-free heme was measured in RBC units before transfusion and in the patients' plasma before and after transfusion. Total plasma heme levels increased in response to transfusion, from a median (interquartile range [IQR]) of 35 (26-76) μmol/L to 47 (35-73) μmol/L (p < 0.001). Posttransfusion total plasma heme was higher in nonsurvivors (54 [35-136] μmol/L) versus survivors (44 [31-65] μmol/L, p = 0.03). Posttransfusion total plasma heme predicted hospital mortality (odds ratio [95% confidence interval] per quartile increase in posttransfusion plasma heme, 1.76 [1.17-2.66]; p = 0.007). Posttransfusion total plasma heme was not correlated with RBC unit storage duration and weakly correlated with RBC unit cell-free heme concentration. Total plasma heme concentration increases in critically ill patients after RBC transfusion and is independently associated with mortality. This transfusion-associated increase in total plasma heme is not fully explained by RBC unit storage age or cell-free heme content. Additional studies are warranted to define mechanisms of transfusion-related plasma heme accumulation and test prevention strategies.

Efficacy of three consecutive therapeutic plasma exchanges in major ABO-incompatible hematopoietic stem cell transplantation.

We retrospectively analyzed data of recipients who underwent three consecutive therapeutic plasma exchanges (TPEs) before major ABO-incompatible (ABOi) hematopoietic stem cell transplantation (HSCT) in our hospital from 2012 to 2017 and evaluated the efficacy of TPE for successful ABOi HSCT. We investigated the efficacy of TPE in 29 recipients with major ABOi HSCT based on the following: (1) requirement of red blood cell (RBC) transfusion during 100 days, (2) erythrocyte engraftment by reticulocyte count at 3 months, and (3) erythropoiesis recovery by bone marrow examination at 1 month and 3 months after ABOi HSCT. IgM and IgG donor-specific isoagglutinins (DSIs) of 31 cases of TPE were significantly decreased after three consecutive TPEs (IgM median, 1:32 to 1:2, P < .0001; IgG median, 1:256 to 1:8, P < .0001). We divided a total of 31 TPEs into two groups depending on their final DSI titers after TPE (group F, DSI > 1:16; group S, DSI ≤ 1:16). RBC transfusions were required more by group F (median, 12 units) than those by group S (median, 2 units, P = .001). Relative frequencies of erythrocyte engraftment and normal erythropoiesis after ABOi HSCT showed higher tendencies in group S than those in group F. Our study demonstrated that three consecutive TPEs were effective in reducing DSI titer in major ABOi HSCT. Reduction of pretransplant DSI in recipients could decrease requirement for RBC transfusion. Three consecutive TPEs are necessary for successful erythrocyte engraftment and normal erythropoiesis in this setting.

Comparative Analysis of Prothrombin Complex Concentrate and Fresh Frozen Plasma in Coronary Surgery

Recent studies suggested that prothrombin complex concentrate (PCC) might be more effective than fresh frozen plasma (FFP) to reduce red blood cell (RBC) transfusion requirement after cardiac surgery. This is a comparative analysis of 416 patients who received FFP postoperatively and 119 patients who received PCC with or without FFP after isolated coronary artery bypass grafting (CABG). Mixed-effects regression analyses adjusted for multiple covariates and participating centres showed that PCC significantly decreased RBC transfusion (67.2% vs. 87.5%, adjusted OR 0.319, 95%CI 0.136-0.752) and platelet transfusion requirements (11.8% vs. 45.2%, adjusted OR 0.238, 95%CI 0.097-0.566) compared with FFP. The PCC cohort received a mean of 2.7±3.7 (median, 2.0, IQR 4) units of RBC and the FFP cohort received a mean of 4.9±6.3 (median, 3.0, IQR 4) units of RBC (adjusted coefficient, -1.926, 95%CI -3.357-0.494). The use of PCC increased the risk of KDIGO (Kidney Disease: Improving Global Outcomes) acute kidney injury (41.4% vs. 28.2%, adjusted OR 2.300, 1.203-4.400), but not of KDIGO acute kidney injury stage 3 (6.0% vs. 8.0%, OR 0.850, 95%CI 0.258-2.796) when compared with the FFP cohort. These results suggest that the use of PCC compared with FFP may reduce the need of blood transfusion after CABG.

Comparison of Hemoglobin Correction Effects According to Storage Period and Other Factors in the Transfusion of Packed Red Blood Cells in Neonatal Intensive Care Unit Patients

Purpose Preterm infants frequently require red blood cell (RBC) transfusions in neonatal intensive care units (NICU). Storage RBCs undergo many changes during storage periods. We aimed to compare the hemoglobin (Hb) correction effect according to the period of RBC storage and investigate the factors influencing Hb correction. Methods This retrospective study reviewed the medical records of 289 patients who received RBC transfusion more than once in the NICU of Kosin University Gospel Hospital between February 2006 and March 2016. The subjects were classified into two storage groups: short-term (≤7 days, n=88) and long-term (>7 days, n=201), according to the period of RBC storage. We checked Hb levels by complete blood cell count tests conducted within 2 days before and 5 to 9 days after the first transfusion. We compared the Hb difference between the two groups and analyzed the factors influencing Hb correction. Results Excluding the use of an invasive ventilator, there was no significant difference between the two groups in terms of clinical characteristics. There was no significant difference in the Hb correction effect between the two groups (P=0.537). Birth weight greater than 1,500 g, higher weight at transfusion, and larger volume of transfusion were significant prognostic factors affecting greater changes in Hb. In addition, surgeryexperience, higher Hb level at transfusion, and additional blood tests were found to be significantly associated with less changes in Hb. Conclusion The RBC storage period did not affect the Hb correction effect. The Hb correction effect may be diminished in infants with lower birth weight and lower weight at transfusion under unstable clinical conditions. Keywords: Premature birth; Erythrocyte aging; Erythrocyte transfusion; Newborn infant; Hemoglobins

The Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions

The Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions