Hemoglobin Transfusion Research Articles

Real Life Blood Management Practices in Thalassemia and Myelodysplastic Syndrome Patients.

The effect of pretransfusion hemoglobin on transfusion burden, thrombosis, and mortality in thalassemia and myelodysplastic syndrome is unclear. We aimed to study the pretransfusion hemoglobin and erythrocyte transfusion burden and investigate the effects of these variables on each other in real-life in thalassemia and myelodysplastic syndrome. Adult patients with thalassemia and myelodysplastic syndrome who received at least one erythrocyte concentrate unit outpatient at Sanliurfa Mehmet Akif Inan Training and Research Hospital during 1 year were included in the study. The data were retrospectively obtained. Ethical approval was obtained for the study. Ninety-two patients were included in the study. In thalassemia major, pretransfusion hemoglobin ≥ 9 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (15 vs. 27) and median annual number of transfusion sessions (11 vs. 14) p=0.002, p=0.009, respectively). In myelodysplastic syndrome, a pretransfusion hemoglobin level ≥ 8 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (6 vs. 24) (p=0.016). In thalassemia major with an intact spleen, pretransfusion hemoglobin ≥ 8 g/dL was associated with an increased median annual number of transfused erythrocyte concentrate units (32 vs. 27) and median annual number of transfusion sessions (18 vs. 14) (p=0.046, p=0.038, respectively). In conclusion, higher pretransfusion hemoglobin levels were related to a lower transfusion burden in thalassemia major and myelodysplastic syndrome.

Retrospective Analysis: Exploring Transfusion Thresholds' Impact on Patients with Sepsis and Renal Failure.

Sepsis with renal failure is a common condition in intensive care units (ICUs) and is associated with poor prognosis. A unified consensus on the optimal transfusion hemoglobin concentration threshold is needed to improve outcomes. This study investigated the effects of different transfusion thresholds during hospitalization on the prognosis of patients with sepsis and renal failure. A total of 2,972 patients were included in this study. By using the Medical Information Mart for Intensive Care (MIMIC-IV) database, data from patients with sepsis and renal failure were screened and divided into a low-threshold group (Hb ≤ 7 g/dL) and a high-threshold group (Hb > 7 g/dL) based on the average hemoglobin (Hb) level 24 hours before transfusion. Univariate and multivariate Cox regression analyses and inverse probability weighting were used to compare in-hospital and ICU mortality rates between the two groups. Additionally, 30-day, 60-day, and 90-day survival rates, length of hospital stay, and ICU stay duration were evaluated. Statistically significant differences in baseline characteristics were observed between the two groups. After propensity score matching to eliminate baseline characteristic differences, it was found that among the Cau¬casian population a higher transfusion threshold significantly reduced the risk of in-hospital mortality (HR, 0.774; 95% CI: 0.613 - 0.978, p < 0.05). For patients with sepsis and renal failure, transfusion thresholds should be determined by considering the patient's race to achieve individualized transfusion strategies.

Evaluating estimated health care resource utilization and costs in patients with myelofibrosis based on transfusion status and anemia severity: A retrospective analysis of the Medicare Fee-For-Service claims data.

Myelofibrosis (MF) is a rare but aggressive myeloproliferative neoplasm that commonly affects older patients, with a mean age of onset of older than 60 years. At least a third of patients with primary MF are anemic at diagnosis, and nearly all patients become anemic over time; approximately half require red blood cell transfusions within a year of diagnosis. Anemia and transfusion dependence are leading negative prognostic factors for overall survival and are associated with diminished quality of life and increased health care-related economic burden in patients with MF. To describe baseline characteristics, health care resource utilization (HCRU), and costs as a function of transfusion status and anemia severity in patients diagnosed with MF among the US Medicare Fee-For-Service (FFS) population. This retrospective cohort study included patients diagnosed with MF appearing in the 100% Medicare FFS database enrolled between January 1, 2012, and December 31, 2020. Patients were segmented into hemoglobin level cohorts (no, mild, moderate, and severe anemia) and transfusion status cohorts (transfusion independent [TI], transfusion requiring [TR], or transfusion dependent [TD]). Across cohorts, demographics and disease characteristics were assessed at baseline; per patient per month all-cause HCRU and medical and pharmacy costs were reported during follow-up. All results were summarized descriptively. The transfusion status cohort (N = 1,749) included TI (n = 980), TR (n = 559), and TD (n = 210) patients; the anemia severity cohort (N = 365) included patients with no (n = 100), mild (n = 128), moderate (n = 99), and severe (n = 38) anemia. On average, TR and TD patients or those with moderate or severe anemia had numerically higher Deyo-Charlson Comorbidity Index scores than those who were TI or had mild or no anemia. TR and TD cohorts reported numerically greater all-cause outpatient, inpatient, and emergency department utilization vs the TI cohort. All-cause costs were numerically higher in the TD and TR cohorts vs the TI cohort ($14,655 and $14,249 vs $8,191). Incremental increases in HCRU and costs were also observed with increasing anemia severity. All-cause medical and pharmacy costs for no, mild, moderate, and severe anemia cohorts were $4,689, $7,268, $10,439, and $13,590, respectively. This retrospective analysis of the US Medicare FFS database descriptively evaluated patients by transfusion status and anemia severity and showed that costs and HCRU were numerically lower for patients with transfusion independence compared with those with transfusion dependence. Similar trends were seen when comparing patients based on anemia status, with numerically lower HCRU and cost observed with decreasing anemia severity.

Hematologic Toxicity Profiles and the Impact of Hemoglobin Nadir and Transfusion on Oncologic Outcome in Definitive Radiochemotherapy for Cervical Cancer.

Background/Objectives: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m2 weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy. Methods: We retrospectively analyzed 147 patients, who received definitive radiochemotherapy between 2000 and 2019 and evaluated laboratory parameters before, after, and at each chemotherapy cycle to evaluate the occurrence, course, and profile of hematotoxicity. Further, we assessed the impact of hemoglobin levels and transfusion on oncological outcomes. Results: In a high-risk cervical cancer population with 82.3% of women with FIGO ≥ III stage, the 1-, 2-, and 5-year rates of overall survival (OS) were 89.1%, 74.7%, and 63.3%, and local control (LC) rates were 90.1%, 86.1%, and 75.0%, respectively. Grade 3 leukopenia was present in 2.1% and grade 3 anemia in 4.3%. No higher grade ≥ 4 hematotoxicity was observed. Absolute hemoglobin levels significantly reduced after the fourth cycle, with a median time from the start of therapy to hemoglobin nadir of 36 days. A lower hemoglobin nadir (<9 g/dL) was significantly associated with inferior LC. Red blood cell transfusion was applied in 44.9% of the women; the necessity of transfusion was significantly correlated to inferior OS, LC, and distant control. Conclusions: Our results suggest the need for special consideration of increased hematotoxicity and consistent implementation of anemia therapy, particularly from the fourth RT week onwards, to enable full-course definitive radiochemotherapy for locally advanced cervical cancer patients.

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold &amp;lt;7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold &amp;lt;10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of &amp;lt;10g/dL, &amp;lt;9g/dL, &amp;lt;8g/dL, and &amp;lt;7g/dL transfusion strategies in adults with acute MI and Hgb &amp;lt;10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the &amp;lt;10g/dL strategy and highest in the &amp;lt;9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the &amp;lt;10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the &amp;lt;9g/dL strategy, 1.14 (0.84-1.55) for the &amp;lt;8g/dL strategy, and 1.44 (0.99-2.09) for the &amp;lt;7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a &amp;lt;10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury

Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy. ClinicalTrials.gov Identifier: NCT02968654.

Assessment of Blood Products Transfusion in Tertiary Neonatal Intensive Care Units Ain Shams University

Abstract Background Preterm Neonates, especially very low birth weight infants, remain a category of patients with high transfusion needs. Appropriate transfusion of neonates is vital when the potential clinical benefit outweighs the risk. However, the association between transfusion and adverse outcomes remains inconclusive. Aim Of The Work To evaluate transfusion practices in Tertiary Neonatal Intensive Care Units at Ain Shams University. Patients and Methods A cross sectional observational study was conducted on patients selected from Tertiary Neonatal Intensive Care Units at Ain Shams University- Children’s hospital. There were 703 neonates (29.64%) who received at least one type of blood products (packed red blood cells, platelets, fresh frozen plasma or cryoprecipitate) transfusion or underwent exchange transfusion during their hospital stay. All neonates receiving blood products transfusions were assessed for full history taking, clinical parameters i.e. gestational age, birth weight and general examination, indications for admission whether medical or surgical indications. Co-morbid illness such as bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, sepsis and patent ductus arteriosus were also noted. In addition, the indications for each of blood products transfusion i.e. anemia, exchange transfusion, thrombocytopenia, sepsis or other indications. Then, the requisition was assessed for pre- and post-transfusion laboratory parameters. Results Packed red blood cell was the most frequent blood component transfused (82.4%) and the main indication was anemia of prematurity (34.8%). There was a highly statistically significant increase in each of hemoglobin and hematocrit (HCT) post transfusion (with P value &amp;lt;0.0001) and a highly statistically decrease in the required median fraction of inspired oxygen (FiO2) (with P value &amp;lt;0.0001). 681 neonates (96.9%) presented with comorbidities; the most common comorbidity was neonatal sepsis in 81.2%. Packed red blood cells (PRBCs) transfusions were highly statistically significant related to comorbidity development. Conclusion Majority of blood transfusions occur during the first 2 weeks of life. Gestational age, birth weight, underlying disease of neonates, the need for oxygen support and blood collection within first two weeks of birth influence their transfusion needs. Sepsis remains the foremost etiological factor for blood component transfusion.

Multicenter comparative study of polysomnography outcomes in children with the monogenic disorder sickle cell disease.

Sleep-disordered breathing (SDB) is prevalent in children with sickle cell disease (SCD) and is associated with worse outcomes. This study aims to compare the outcomes of polysomnography (PSG) performed for pediatric patients with SCD at three United States centers. We included children with SCD aged 0-21 who underwent PSG at three American Academy of Sleep Medicine accredited centers: the University of Alabama at Birmingham (UAB), the University of Florida (UF), and Duke University Hospital (DUH), between 2012 and 2022. Descriptive statistics were used as appropriate to compare the baseline characters and PSG outcomes among the different centers. A total of 210 children with SCD from the three centers were included, with comparable sex, SCD genotypes, hemoglobin, hematocrit levels, and chronic transfusion. Children from the different centers exhibited variations in age (P < .001), BMI (P < .05), mean corpuscular volume (P < .05), and hydroxyurea use (P < .05) at the time of the PSG. Overall, the three centers showed significantly different PSG outcomes. Patients from UF had worse obstructive sleep apnea, oxygenation, and periodic leg movement events, together with lower hydroxyurea usage. While those from DUH showed higher hypoventilation and arousal indices. This multicenter study underscores variations in PSG outcomes among pediatric SCD patients at different centers in the Southeast United States. These findings emphasize the need for standardized approaches to screen for SDB, refer to PSG, and interpret the results in children with SCD. These conclusions may apply to other genetic disorders associated with an increased risk of sleep-disordered breathing.

Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023

Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown. To describe neonatal RBC transfusion practice in Europe. This international prospective observational cohort study collected data between September 1, 2022, and August 31, 2023, with a 6-week observation period per center, from 64 NICUs in 22 European countries. Participants included 1143 preterm infants born before 32 weeks of gestation. Admission to the NICU. Study outcome measures included RBC transfusion prevalence rates, cumulative incidence, indications, pretransfusion hemoglobin (Hb) levels, volumes, and transfusion rates, Hb increment, and adverse effects of RBC transfusion. A total of 1143 preterm infants were included (641 male [56.1%]; median gestational age at birth, 28 weeks plus 2 days [IQR, 26 weeks plus 2 days to 30 weeks plus 2 days]; median birth weight, 1030 [IQR, 780-1350] g), of whom 396 received 1 or more RBC transfusions, totaling 903 transfusions. Overall RBC transfusion prevalence rate during postnatal days 1 to 28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%-41.5%) of infants had received at least 1 transfusion. Most transfusions were given based on a defined Hb threshold (748 [82.8%]). Hemoglobin levels before transfusions indicated for threshold were below the restrictive thresholds set by ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%). Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) transfusions, respectively, and above liberal thresholds in 53 (7.3%) and 55 (7.5%) transfusions, respectively. Most transfusions given based on threshold had volumes of 15 mL/kg (470 of 738 [63.7%]) and were administered over 3 hours (400 of 738 [54.2%]), but there was substantial variation in dose and duration. In this cohort study of very preterm infants, most transfusions indicated for threshold were given for pretransfusion Hb levels above restrictive transfusion thresholds evaluated in recent trials. These results underline the need to optimize practices and for implementation research to support uptake of evidence.

Are outcomes of locally advanced cervical cancer associated with prebrachytherapy hemoglobin values and transfusion practice? An observational study comparing two large academic centres with divergent clinical guidelines

Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L. This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2). Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality. The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use.

The use of topical tranexamic acid in geriatric fractured hip

Background: Topical tranexamic acid (TXA) is used preoperatively to reduce blood loss. This study evaluated the effect of topical TXA on post-operative transfusion rate and haemoglobin level in geriatric patients with hip fractures. Methods: This retrospective cohort study included 135 patients over 65 years old with hip fractures from June 2020 to June 2023. Their total haemoglobin mass loss, transfusion rate and thromboembolic events were compared based on the fracture type and intervention (10–15 mg/kg of topical TXA). Results: No significant differences were found in total haemoglobin mass, transfusion rate or thromboembolic events. There was no evidence of an association between the use of TXA and post-operative blood transfusion (OR = 0.82, 95% CI: 0.27–2.52, p = 0.734) or thromboembolic events (OR = 0.81, 95% CI: 0.07–9.49, p = 0.866). Conclusion: A 10–15 mg/kg topical TXA did not reduce total haemoglobin mass loss, influence transfusion needs or increase thromboembolic events or 30-day mortality.

Perioperative Transfusion Practices in Adults Having Noncardiac Surgery

Surgical patients are often transfused to manage bleeding and anemia. Best practices for red blood cell (RBC) transfusion administration in patient having noncardiac surgery remains controversial and a robust evaluation and description of perioperative transfusion practices is lacking. We characterized perioperative hemoglobin concentrations and transfusion practices from the prospective VISION cohort which included 39,222 patients aged ≥45 years who had inpatient noncardiac surgery. Variations in transfusion practices were analyzed using hierarchical mixed models, and associations with mortality and complications were evaluated using a nested frailty survival model. Within the cohort, 16.1% (n = 6296) were given perioperative RBC transfusions, with the fraction declining from 20% to 13% over the 6-year study period. The proportion of patients transfused varied by surgery type from 6.4% for low-risk operations (i.e., minor surgery) to 31.5% for orthopedic surgeries. Variations were largely associated with patient hemoglobin concentrations, but also with center (range: 3.7%-27.3%) and country (0.4%-25.3%). Even after adjusting for baseline hemoglobin, comorbidities and type of surgery, both center and country were significant sources of variation in transfusion practices. Among transfused participants, 60.4% (n = 3728/6170) had at least 1 hemoglobin concentration ≤80g/L and 86.0% (n = 5305/6170) had at least 1 hemoglobin concentration ≤90g/L, suggesting that relatively restrictive transfusion strategies were used in most. The proportion of patients receiving at least 1 RBC transfusion declined from 20% to 13% over 6 years. However, there was considerable unexplained variation in transfusion practices.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5–9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as “restrictive” or “liberal” based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5–9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7–8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70–0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15–3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07–2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76–1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59–6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022–11–07.

Clinical and Demographic Characteristics of Pyruvate Kinase Deficiency Patients: A Comprehensive Case Series Analysis.

Introduction Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder characterized by mutations in the PKLR gene, causing impaired glycolysis in red blood cells and leading to diverse clinical manifestations. The prevalence of PKD in Saudi Arabia remains understudied, particularly in the context of consanguinity and non-specialized medical facilities. Methods We conducted a retrospective analysis of seven PKD patients of Arab ethnicity, focusing on demographics, medical history, clinical features, laboratory results, treatments, and outcomes. Results Our patient cohort comprised five males and two females, aged 10 to 38 years, of Arab ethnicity. Consanguinity was prevalent, and hereditary connections were identified in five patients. PKD exhibited varying clinical presentations, with early-onset symptoms including neonatal jaundice and symptomatic anemia. One patient experienced severe hepatic disease progression leading to multiorgan failure. Blood transfusions were universally required, indicating the severity of the disorder. Anemia severity varied among patients, with diverse hematological irregularities. Splenectomy was performed for most patients, improving hemoglobin levels and transfusion needs in some cases. Iron chelation was administered, although iron overload persisted. Thrombocytosis and venous thromboembolism were observed post splenectomy. Jaundice and gallstones were common, leading to cholecystectomy. Laboratory findings remained consistent, with heightened reticulocyte counts and altered enzyme levels. Discussion PKD is a rare disorder characterized by diverse clinical manifestations. Prevalence estimation is complex due to various factors, and its diagnosis is challenged by clinical similarities with other disorders. Our cohort exhibited a spectrum of complications, highlighting the necessity for tailored interventions. Iron overload remained a concern, necessitating continuous monitoring. Although endocrine disorders and osteoporosis were absent in our cohort, vigilance is essential due to the disease's progressive nature. Genetic factors were prominent, supporting the genetic basis of PKD. Splenectomy improved anemia but had a limited impact on gallstones. Iron overload management and bone health remain crucial considerations. Conclusion This study offers comprehensive insights into the clinical and demographic characteristics of PKD patients, illustrating the complex nature of the disorder. The findings underscore the need for personalized management strategies and vigilant monitoring to address the diverse clinical manifestations and challenges associated with PKD.

Evaluating the Effect of Decreasing Preoperative Hemoglobin on Blood Transfusions, Major Complications, and Periprosthetic Joint Infection After Primary Total Knee Arthroplasty.

Preoperative anemia is associated with increased postoperative transfusion and complication rates after total knee arthroplasty (TKA). We aimed to create TKA-specific data-driven preoperative hemoglobin strata that quantify the likelihood of 90-day postoperative blood transfusion and evaluate whether these strata are associated with increased risk of 90-day major complications and 2-year prosthetic joint infection (PJI). Primary TKA patients from 2013 to 2022 were identified using a national database. Stratum-specific likelihood ratio (SSLR) analysis defined hemoglobin strata associated with the risk of 90-day blood transfusion. Each stratum was propensity score matched to the highest identified hemoglobin strata. Unmatched incidence rates and matched risk of 90-day major complications and 2-year PJI between strata were compared. SSLR identified four 90-day blood transfusion hemoglobin strata for men (strata [g/dL], likelihood ratio [<11.4, 8.06; 11.5 to 11.9, 4.34; 12.0 to 12.9, 1.70; 13.0 to 17.0, 0.54]) and women (<10.4, 8.22; 10.5 to 11.4, 2.84; 11.5 to 12.4, 1.38; 12.5 to 17.0, 0.50). Increased 2-year PJI risk was associated with three male strata (<11.4, 11.5 to 11.9, 12.0 to 12.9; all P < 0.001) and three female strata (<10.4, 10.5 to 11.4, 11.5 to 12.4; all P < 0.001). Increased 90-day major complication risk was associated with three male strata (<11.4, 11.5 to 11.9, 12.0 to 12.9; all P < 0.001) and three female strata (<10.4, 10.5 to 11.4, 11.5 to 12.4; all P < 0.001). Using SSLR analysis, we identified unique TKA-specific data-driven hemoglobin strata for both men and women that quantify the likelihood of 90-day blood transfusions and predict the risk of both 90-day major complications and 2-year PJI. These strata are a first in the TKA literature and can assist surgeons in stratifying patients' transfusion and complication risk based on their preoperative hemoglobin value. While optimizing patients in the preoperative setting, we recommend using these TKA-specific hemoglobin thresholds to help guide decision making on the need for presurgery anemia optimization and to help reduce the need for blood transfusion.

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis

Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. ClinicalTrials.gov Identifier: NCT01702805.

Utilisation of intravenous iron and erythropoietin in dialysis patients: A prospective observational study

In this prospective observational study, the utilization of intravenous iron and erythropoietin in dialysis patients was thoroughly investigated. The study aimed to assess the effectiveness of these treatments in managing anaemia, a common complication in individuals undergoing dialysis. Anaemia is a significant concern in this population due to impaired erythropoiesis and iron deficiency resulting from renal dysfunction. The study followed a cohort of dialysis patients, tracking their response to intravenous iron supplementation and erythropoietin therapy over a specified period. Through regular monitoring and evaluation, the study sought to determine the impact of these interventions on haemoglobin levels, transfusion requirements, and overall patient outcomes. Additionally, the study likely analysed factors such as dosing regimens, adverse effects, and the need for additional interventions to achieve optimal haemoglobin levels. By conducting a prospective observational study, researchers aimed to provide valuable insights into the real-world effectiveness and safety of intravenous iron and erythropoietin in managing anaemia in dialysis patients, which could inform clinical practice and improve patient care strategies.

Combination of a TGF-β ligand trap (RAP-GRL) and TMPRSS6-ASO is superior for correcting β-thalassemia.

A recently approved drug that induces erythroid cell maturation (luspatercept) has been shown to improve anemia and reduce the need for blood transfusion in non-transfusion-dependent as well as transfusion-dependent β-thalassemia (BT) patients. Although these results were predominantly positive, not all the patients showed the expected increase in hemoglobin (Hb) levels or transfusion burden reduction. Additional studies indicated that administration of luspatercept in transfusion-dependent BT was associated with increased erythropoietic markers, decreased hepcidin levels, and increased liver iron content. Altogether, these studies suggest that luspatercept may necessitate additional drugs for improved erythroid and iron management. As luspatercept does not appear to directly affect iron metabolism, we hypothesized that TMPRSS6-ASO could improve iron parameters and iron overload when co-administered with luspatercept. We used an agent analogous to murine luspatercept (RAP-GRL) and another novel therapeutic, IONIS TMPRSS6-LRx (TMPRSS6-ASO), a hepcidin inducer, to treat non-transfusion-dependent BT-intermedia mice. Our study shows that RAP-GRL alone improved red blood cell (RBC) production, with no or limited effect on splenomegaly and iron parameters. In contrast, TMPRSS6-ASO improved RBC measurements, ameliorated splenomegaly, and improved iron overload most effectively. Our results provide pre-clinical support for combining TMPRSS6-ASO and luspatercept in treating BT, as these drugs together show potential for simultaneously improving both erythroid and iron parameters in BT patients.

Safety and complications of continuation of aspirin therapy in patients undergoing robot-assisted laparoscopic simple prostatectomy

To evaluate the safety and feasibility of continued perioperative aspirin at the time of robotic assisted simple prostatectomy (RASP). We performed a retrospective review of our IRB approved institutional database of patients who underwent RASP between 2013 and 2022. Comparative groups included patients taking aspirin in the perioperative period and those not taking aspirin pre-operatively. The primary outcome was any post-operative bleeding related complication using the modified Clavien–Dindo classification. Secondary outcomes included the identification of risk factors for increased blood loss in the entire study population, operative time, and blood transfusion requirement. 143 patients underwent RASP of which 55 (38.5%) patients continued perioperative aspirin therapy and 88 (61.5%) patients did not. Baseline demographics were similar between groups. Patients taking perioperative aspirin had a higher rate of hypertension (74.5% vs 58.0%, p = 0.04) and other cardiovascular disease (30.9% vs 11.4%, p = 0.007). Postoperative complications were similar between the groups (Clavien-Dindo ≥ 3; p = 0.43). Median blood loss (150 cc vs 150 cc, p = 0.38), percentage drop in hemoglobin (13.4 vs 13.2, p = 0.94) and blood transfusion rate (3.6 vs 1.1, p = 0.56) were also similar between groups. The median blood loss was 150 ml for the whole study population. On regression analysis, neither aspirin nor any other variable was associated with increased blood loss (> 150 ml). Aspirin can be safely continued perioperatively in patients undergoing RASP without any risk of bleeding related complications, blood loss, or increased transfusion rate.

Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48Weeks: 307 Open-Label Extension Study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first targeted complement component3 (C3) PNH therapy, was safe and efficacious in treatment-naive and pre-treated patients with PNH in five clinical trials. The 307 open-label extension (OLE) study (NCT03531255) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin > 12g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6g/dL; female, ≥ 12g/dL) were assessed as percentage of patients with data available and no transfusions 60days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported. Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin > 12g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred. Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan. ClinicalTrials.gov identifier, NCT03531255.