Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage – A multicentre subanalysis of the German PBM Network Registry

Purpose Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. Methods This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 until 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Results A total of n = 9,081 patients were analysed (aSAH n = 5,008; ICH n = 4,073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR= 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR= 1.48 in aSAH, OR= 1.53 in ICH, p < 0.001) and for several postoperative complications. Conclusions Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Trial registration: ClinicalTrials.gov, NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795

Factors Contributing to Red Blood Cells Crossmatch and Transfusion among Obstetrics Patients in a Single Tertiary Hospital

INTRODUCTION: Transfusion of blood and blood components among obstetrics patients is a common practice but they are not without risks. This study aims to determine crossmatch to transfusion ratio (C:T ratio) and to assess the factors that influence red blood cells (RBC) transfusion among obstetrics patients in a single tertiary hospital. MATERIAL AND METHODS: This was a retrospective cohort study of RBC crossmatch requests with data collected from 350 obstetrics patients. The patients were grouped into either received RBC transfusion or did not receive transfusion. Demographics and clinical characteristics were analyzed using descriptive and multivariate analysis. RESULTS: The mean C:T ratio was 3.1. Of 350 patients, 149 (42.6%) patients did receive RBC transfusion. Patients with underlying hemoglobinopathy (75.9%), history of postpartum hemorrhage (63.6%), underwent instrumental assisted delivery (64.3%), and with hemoglobin level of < 70 g/L upon crossmatch requests (90.5%) did receive RBC transfusion. Cesarean section (p=0.011), hemoglobin level < 99 g/L (p<0.001), estimated blood loss > 1000 mL (p<0.001), and symptomatic anemia (p=0.029) were the significant factors associated with RBC transfusion. CONCLUSION: The mean C:T ratio in our study was high. Identifying the factors contributing to RBC transfusion among obstetrics patients are important to reduce unnecessary crossmatch and subsequently improve blood inventory management, and thus further reduce the risks associated with allogeneic transfusion.

Safety of Uncrossmatched ABO-Compatible RBCs in Alloimmunized Patients with Bleeding: Data from Two Decades: Results of a Systematic Analysis in 6,109 Patients

<b><i>Introduction:</i></b> Uncrossmatched ABO-compatible red blood cells (RBCs) are generally recommended in patients with life-threatening massive bleeding. There is little data regarding RBC transfusion when patients are transfused against clinically significant alloantibodies because compatible RBCs are not immediately available. <b><i>Methods/Patients:</i></b> All patients reviewed in this study (<i>n</i> = 6,109) required emergency blood transfusion and were treated at the Charité – Universitätsmedizin Berlin between 2001 and 2015. Primary uncrossmatched O Rh(D)-positive or -negative RBC units were immediately transfused prior to complete regulatory serological testing including determination of ABO group, Rhesus antigens, antibody screening, and crossmatching. <b><i>Results:</i></b> Without any significant change in the protocol of emergency transfusion of RBCs, a total of 63,373 RBC units were transfused in 6,109 patients. Antibody screening was positive in 413 patients (6.8%), and 19 of these patients received RBC units against clinically significant alloantibodies. None of these patients appeared to have developed significant hemolysis, and only one patient with anti-D seems to have developed signs of insignificant hemolysis following the transfusion of three Rh(D)-positive units. One patient who had anti-Jk^a received unselected units and did not develop a hemolytic transfusion reaction. <b><i>Conclusion:</i></b> Transfusion of uncrossmatched ABO-compatible RBCs against alloantibodies is highly safe in patients with life-threatening hemorrhage.

Red Blood Cell Transfusion and Postoperative Delirium in Hip Fracture Surgery Patients: A Retrospective Observational Cohort Study

Background. Patients having hip fracture surgery are at high risk for postoperative delirium. Red blood cell (RBC) transfusion may increase postoperative delirium risk by causing neuroinflammation. We hypothesized that RBC transfusion would be associated with postoperative delirium in patients having hip fracture surgery. Methods. An observational cohort study was performed using the United States National Surgical Quality Improvement Program (NSQIP) participant use files for hip fracture from 2016 to 2018. Propensity score analysis and inverse probability of treatment weighting (IPTW) were used to reduce bias from confounding. An IPTW adjusted odds ratio for developing postoperative delirium was calculated for patients who received RBC transfusion during surgery or in the 72 hours after. Results. There were 20,838 patients who had eligible current procedural terminology (CPT) codes for primary hip fracture surgery and complete study data. After employing strict exclusions to balance covariates and reduce bias, 3,715 patients remained in the IPTW cohort. Of these, 626 patients (16.9%) received RBC transfusion and 665 patients (17.9%) developed postoperative delirium. IPTW adjustment led to good covariate balance between patients who received RBC transfusion and those who did not. Patients who received RBC transfusion had significantly higher odds of postoperative delirium, IPTW adjusted odds ratio = 1.21, 95% CI = 1.03 to 1.43, and P = 0.02. Discharge location also differed significantly between patients who received RBC transfusion and those who did not ( P < 0.001) with in-hospital mortality or referral to hospice occurring in 1.6% of patients who received RBC transfusion and 1.3% of patients who were not transfused. Conclusion. RBC transfusion is associated with increased odds of postoperative delirium after hip fracture surgery and may be associated with worse clinical outcome.

Central Line Access is Predictive of Diagnostic Blood Loss and Transfusion in the Surgical Intensive Care Unit

Background: Diagnostic laboratory testing (DLT) is a source of blood loss in critically ill patients. Approximately half of patients admitted to the intensive care unit (ICU) present with anemia, with the remainder developing a multifactorial anemia with etiologies including central venous catheter (CVC) placement. Consequently, about a third of ICU patients require red blood cell (RBC) transfusion, a practice associated with poorer clinical outcomes. Our objectives were to characterize DLT blood loss in the surgical intensive care unit (SICU), and its relationship with anemia, RBC transfusion, and CVC placement.Methods: An observational study was performed by retrospective chart review of patients admitted to a SICU over 1-year. The number of DLT blood draws, average volume of blood drawn, and estimated discard volume were recorded along with clinical and laboratory findings. Results: A cohort of 292 patients (mean age 62.2 years, male to female ratio 1.5) underwent 299 hospitalizations with an average daily DLT blood loss of 14.3 mL (229.5 mL per admission). Among admissions, 51.2% presented with anemia and 95.3% were anemic at discharge, with 32% of patients receiving an RBC transfusion. Patients with greater DLT-associated blood loss had lower discharge hemoglobin (p=<0.001). Admissions requiring CVC (49.8%), demonstrated a significantly greater number of DLT blood draws, increased DLT-associated blood loss, higher rates of RBC transfusion, and an increased length of stay.Conclusions: Findings from this study suggest that DLT blood loss contributes to anemia in the SICU and the presence and duration of CVC leads to increased testing, blood loss, anemia, and is predictive of RBC transfusion.

Blood transfusion had no influence on the 5-year biochemical recurrence after robot-assisted radical prostatectomy: a retrospective study

Background Although red blood cells (RBC) transfusion is known to be significantly associated with biochemical recurrence in patients undergoing open prostatectomy, its influence on biochemical recurrence after robot-assisted laparoscopic radical prostatectomy remains unclear. Therefore, this study aimed to validate the effect of RBC transfusion on the 5-year biochemical recurrence in patients undergoing robot-assisted laparoscopic radical prostatectomy. Methods This study retrospectively analyzed the medical records of patients who underwent robot-assisted laparoscopic radical prostatectomy at single tertiary academic hospital between October 2007 and December 2014. Univariate and multivariate Cox proportional hazard regression analysis was performed to identify any potential variables associated with 5-year biochemical recurrence. Results A total of 1311 patients were included in the final analysis. Of these, 30 patients (2.3%) were transfused with RBC either during robot-assisted laparoscopic radical prostatectomy or during their hospital stay, which corresponded to 5-year biochemical recurrence of 15.7%. Multivariate Cox proportional hazard regression analysis showed that RBC transfusion had no influence on the 5-year biochemical recurrence. Variables including pathologic T stage (Hazard ratio [HR] 3.5, 95% confidence interval [CI] 2.4–5.1 p < 0.001), N stage (HR 2.3, 95% CI 1.5–3.7, p < 0.001), Gleason score (HR 2.4, 95% CI 1.8–3.2, p < 0.001), and surgical margin (HR 2.0, 95% CI 1.5–2.8, p < 0.001) were independently associated with the 5-year biochemical recurrence. Conclusions RBC transfusion had no significant influence on the 5-year biochemical recurrence in patients undergoing robot-assisted laparoscopic radical prostatectomy.

Clinical Efficacy of JAK Inhibitors in Patients with Vexas Syndrome: A Multicenter Retrospective Study

Background VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is due to a somatically acquired mutation of the E1-ubiquitin ligase UBA1, leading to the expression of a catalytically impaired isoform in myeloid cells. VEXAS syndrome combines severe auto-inflammatory manifestations and is frequently associated with myeloid neoplasia (MN). The outcome of VEXAS is poor, and most patients require high dose corticosteroids to reduce inflammation (Bourbon et al. Blood 2021). Therapeutic options besides steroids are currently limited in those patients. In this multicenter retrospective study, we report some clinical efficacy of JAK inhibitors (JAKi) in VEXAS patients. Patients We analyzed retrospectively 24 UBA1 mutated patients (Met41 or previously reported alternative splicing site) treated with JAKi (11 with ruxolitinib (RUXO), 11 with tofacitinib (TOFA), 1 with baricitinib, 1 with upadicitinib) in 7 French, 1 Portugese and 2 US centers. Complete clinical (CCR) and complete biological response (CBR) were defined as complete resolution of clinical symptoms and normalization of inflammation markers (C reactive protein, CRP) respectively. Partial clinical (PCR) and biological (PBR) response were defined by reduction of at least 50% of clinical or inflammation markers, respectively. Results All 24 patients were males with a median age at VEXAS diagnosis of 72 years [range 54-89]. Thirteen had documented myeloid neoplasia (MN) (1 CMML-0, 1 other MDS/MPN, 10 MDS). Clinical manifestations at VEXAS diagnosis include skin involvement (87.5%), arthritis or arthralgia (83.3%), vasculitis (37.5%), fever (75%), ocular manifestations (29.2%) and pulmonary infiltrates (41.6%). IPSS-R was very low/low/intermediate in 8/3/2 cases respectively. Median time between first VEXAS related clinical manifestations and JAKi onset was 2.45 years [0.15-5.45]. Prior to JAKi onset, patients had received a median of 2.5 immunosuppressive/immunomodulatory treatments [range 0-9]. After 1 month, 12/24 (50%) patients had achieved clinical and/or biological response. CCR and CBR was achieved in 7/11 (64%) and 6/11 (54%) patients treated with RUXO, and in 3/13 (23%) and 2/13 (15%) patients treated with other JAKi (figure A). After 3 months, CCR and CBR was 100% and 80% (10 evaluable patients) in the RUXO group as compared to 25% and 25 % in patients treated with other JAKi (8 evaluable patients) (p=0.0036 et 0.0055 respectively, figure B). RUXO efficacy was similar in patients with (n=9) or without (n=2) associated MN. In RUXO treated patients, median CRP and steroid dose reduction was 72.5% [range 21.5- 99.5] and 66.25% [range 0-75] respectively at 3 months. With a median follow-up of 4 months [range 1.4-12], only 1 RUXO treated patient had lost response, whereas median time to next of treatment was 3.4 months with other JAKi (figure C). Of the 13 patients with MN, 7 were RBC transfusion dependent at JAKi onset (6 with RUXO, 1 with other JAKi). Four of 6 patients treated with RUXO achieved RBC transfusion independence at 3 months, but not the patient treated with other JAKi. Regarding safety, severe adverse events were reported in 6 patients: 3 deep vein thrombosis, (2 with TOFA/1 with RUXO), 1 pneumonia (RUXO), 1 enterohemorrhagic E. Coli infection (RUXO), and 1 lethal legionellosis (TOFA)). Conclusion Ruxolitinib (and less often other JAK inhibitors used in this study) provides rapid response in most VEXAS patients, allowing in two third of the cases corticosteroid dose reduction/withdrawal and RBC transfusion independence in 4/6 patients with MN who were initially transfusion dependent. Those retrospective preliminary results, with limited follow up, must be interpreted with caution and will be updated at the meeting. The effect of RUXO on VEXAS patients with concomitant MN will soon be studied prospectively in a Groupe Francophone des Myélodysplasies (GFM) clinical study. Figure 1 Figure 1. Disclosures Galicier: Novartis Pharma Sas, Sanofi Aventis France: Consultancy; Lilly France, Baxalta France, Sanofi Aventis France Sas: Other: Payments as Speaker for Educational Program; Shire France SA, Janssen-Cilag, Pfizer Sas: Other: Invitation to Congress. Hirsch: Novartis Pharma: Consultancy; Daiichi Sankyo Oncology: Consultancy. Warrington: Eli Lilly: Research Funding; Kiniksa: Research Funding. Fenaux: Novartis: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.

Understanding the Association between Red Blood Cell Transfusion Dependency and Humanistic, Psychosocial, and Psychological Burden in Patients with β-Thalassemia from the Patients' Perspective

Introduction: A recent systematic literature review (Betts M, et al . Clin Ther 2020;42:322-337) perceived that in the past 2 decades, advancements in the treatment and management of β-thalassemia have resulted in improvements in iron control. However, clinical complications, including alloimmunization, iron overload, and resultant cardiac and liver disease, remain a challenge. While red blood cell (RBC) transfusions are used to treat anemia in patients with β-thalassemia, those who are transfusion dependent reported poorer health-related quality of life (HRQoL) compared with the US general population. The literature misses a holistic understanding of the humanistic, psychosocial, and psychological burden of transfusion dependency in β-thalassemia in terms of the impact of disease and treatment on patients' daily lives, distress arising from the possibility of adverse events, and comorbidities. Methods: First, concept elicitation qualitative interviews (n=3) and cognitive pre-test interviews (n=3) were conducted with patients from the Cooley's Anemia Foundation (CAF) to test and revise a 30-minute web-based patient survey questionnaire for clarity and relevance. Following, a larger cross-sectional study included adult patients with β-thalassemia in the USA identified by the CAF. Patients were recruited via email invitation or social media, and invited by CAF to take the survey, at which point informed consent was obtained. Inclusion criteria included ≥18 years of age, self-reported physician diagnosis of β-thalassemia, and ≥1 RBC transfusion in the past 6 months. Survey instruments included the Functional Assessment of Cancer Therapy-Anemia (FACT-An), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), ad hoc questions around patient treatment experience, side effects resulting from β-thalassemia treatment, and psychological burden due to treatment. All results were reported descriptively, with frequency counts and percentages for categorical/ordinal data and mean and standard deviations (SD) for continuous data. Results: Overall, 100 patients in the USA completed the survey; 65% were female, average age was 36.0 (SD=10.4) years, 42% were Asian/Pacific Islander, and 33% reported a household income of USD 100,000 or more. On average, patients had been diagnosed with β-thalassemia for 34.4 (SD=10.3) years and received 9.6 (SD=4.3) RBC transfusions in the past 6 months. Among all patients, 70% reported moderate to extremely high burden of RBC transfusions, 81% reported experiencing iron overload due to RBC transfusion, and 42% reported not being as social with friends/family due to the time needed for RBC transfusions and the associated recovery time. Over 50% of patients reported mild to severe depression (52%) via PHQ-9 and anxiety (53%) via GAD-7 symptoms over the previous 2 weeks. The FACT-An (0-188), where higher scores indicate better outcomes, average score was 132 (SD=33.5), while fatigue symptoms (0-52) average score was 33.3 (SD=12.3), and anemia symptoms (0-28) average score was 20.4 (SD=5.5) in the past 7 days. A week prior to receiving an RBC transfusion, 18% of patients reported their overall health as "very well" versus 52% 1 week after an RBC transfusion. Conclusions: Although upon RBC transfusion HRQoL temporarily improves, overall, these results demonstrated patients with transfusion-dependent β-thalassemia experienced poor health prior to RBC transfusion, mild to severe depression and anxiety, increased psychological burden, and suboptimal HRQoL. These findings contribute to the understanding of the humanistic and psychological burden of RBC transfusion dependency in patients with β-thalassemia and suggest that new treatment options that can improve outcomes in this population are needed. Disclosures Price: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Gupta: Bristol Myers Squibb: Consultancy, Research Funding; Kantar Health: Current Employment. Perkowski: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Costantino: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Inyart: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Ashka: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Clapp: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Knoth: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

The Evaluation of Transfusion Data from the Phase 3 Clinical Study of L-Glutamine in Sickle Cell Disease

Introduction The multicenter trial of L-glutamine in sickle cell disease enrolled a total of 230 patients, randomized 2:1, to receive L-glutamine (152 patients) or placebo (78 patients). Following 48 weeks of therapy, patients in the L-glutamine group had significantly fewer pain crises and fewer hospitalizations than those in the placebo group. Two thirds of the patients in both trial groups received concomitant hydroxyurea. The Multicenter Study of Hydroxyurea showed that the treatment group differed from the placebo group in the number of units of blood transfused and in the number of patients receiving transfusions. 1 Since an evaluation of transfusions was not pre-specified in the L-glutamine study, post-hoc analyses were performed on the number of units of red blood cells (RBC) transfused and on the number of transfusions that took place during the study. Methods For the number of units of RBCs transfused through Week 48, analyses of the transfusion dataset were performed using the Poisson regression model with both a robust error variance method and a bootstrap method with baseline reticulocyte count as a covariate. The bias-corrected and accelerated bootstrap method was based on 10,000 draws with replacement from the original data used to compute the 95% confidence interval (CI) for relative risk of the number of units of RBCs transfused and the p-value. For the number of transfusion episodes, the recurrent-event time analysis using the Lin-Wei-Yang-Ying (LWYY) method was employed to model the mean cumulative number of RBC transfusion episodes over the 48-week treatment period with baseline reticulocyte count as a covariate. 2 Results There was a significant difference in the number of units of RBCs transfused in the L-glutamine treatment arm than in the placebo arm; 2.86 units per patient-year in the L-glutamine group vs. 5.38 units per patient-year in the placebo group (Table 1). There was a lower trend in the mean cumulative number of RBC transfusion episodes in the L-glutamine arm than the placebo arm during the 48-week treatment period; 1.702 RBC transfusion episodes per patient-year in the L-glutamine arm compared to 2.659 RBC transfusion episodes per patient-year in the placebo arm (Table 2, Figure 1). Conclusion The post-hoc analyses of the L-glutamine phase 3 clinical study in SCD indicated that, of patients requiring RBC transfusions, those assigned to L-glutamine required approximately 43% fewer units of RBCs compared to those assigned to placebo over the 48-Week period. The recurrent event-time analysis showed a favorable trend in the fewer number of RBC transfusion episodes for those receiving L-glutamine as compared to placebo. These observations are significant when considering the fact that 66% of participants in both arms of this study were on hydroxyurea therapy. REFERENCES 1) Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of L-glutamine in sickle cell disease. N Eng J Med. 2018;379:226-35. 2) Lin DY, Wei LJ, Yang I, Ying Z. Semiparametric regression for the mean and rate functions of recurrent events. J Royal Statistical Society Series B. 2000;62(4):711-30. Figure 1 Figure 1. Disclosures Becerra: Emmaus Medical, Inc: Current Employment. Stark: Emmaus Medical, Inc: Current Employment. Niihara: Emmaus Lifesciences, Inc.: Current Employment. Callaghan: Agios Pharmaceuticals: Current Employment; BioMarin: Consultancy; Chiesi: Consultancy; Forma: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; Hema Biologics: Consultancy; Kedrion: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Speakers Bureau; Sanofi: Consultancy; Spark: Consultancy; Takeda: Consultancy, Speakers Bureau; uniQure: Consultancy.