BACKGROUND: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration.
METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively.
RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower.
CONCLUSIONS: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies.
BACKGROUND: ClinicalTrials.gov: NCT02101268.
Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.

BACKGROUND: Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest.
METHODS: We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization.
RESULTS: In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group.
CONCLUSIONS: This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients.

BACKGROUND: Whether perioperative red blood cell transfusions increases the risk of postoperative venous thromboembolism is controversial and uncertain.We aims to explore the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism by conducting a meta-analysis.
OBJECTIVE: To conduct a meta-analysis to systematically evaluate the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism.
METHODS: PubMed, Embase, Cochrane, and Web of Science databases were searched to identify studies examining the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism. The databases were searched from establishment to August 2023.Two researchers independently screened literature and extracted data according to inclusion and exclusion criteria. Newcastle-ottawa Scale was used for quality assessment. Meta-analysis of data was performed using RevMan 5.4 software.
RESULTS: A total of 15 studies involving 1,880,990 patients were included in this study.Meta-analysis showed that perioperative red blood cell transfusions increased the risk of postoperative venous thromboembolism [OR = 1.61, 95%CI (1.37, 1.89), P < 0.001]. Subgroup analyses showed that the transfusion dose,transfusion timing,study population and follow-up time were closely related to the risk of postoperative venous thromboembolism.
CONCLUSIONS: In summary, this meta-analysis demonstrated a significant positive association between perioperative red blood cell transfusions and postoperative venous thromboembolism.Healthcare professionals should pay attention to the influence of blood transfusions on postoperative venous thromboembolism, strengthen management and prevention.

Alterations in skin blood flow (SBF) may help to detect occult hypoperfusion in critically ill patients after fluid resuscitation. In this study, SBF is globally unaltered by red blood cell transfusion (RBCT) in non-bleeding critically ill patients after initial resuscitation; however, 37.5% of patients showed a significant increase in SBF. No correlation between relative changes in SBF and systemic variables after RBCT was observed.

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.

Pediatric patients on extracorporeal membrane oxygenation (ECMO) often receive repeated red blood cell (RBC) transfusions. This study aims to quantify and characterize causes of RBC loss on ECMO.
This retrospective, single-center, observational study includes 91 ECMO patients (age 1 day-20 years). An RBC loss index (RLI), equal to ml RBCs lost per liter of patient + circuit volume per hour, was calculated from the changes in hematocrit and transfused RBCs. To measure the contribution of RBC injury/activation, RBC extracellular vesicle (REV) generation was measured by flow cytometry.
Median RLI on ECMO was 1.9 ml/L/h, 13-fold higher than normal RBC production rate (0.15 ml/L/h) and equivalent to a 4.6 drop in hematocrit/day. Median RBC loss was higher in patients who died (2.95 ml/L/h) versus survived (1.70 ml/L/h, p = .0008). RLI correlated with transfusion rate (r2  = 0.71); however, transfusion rate (ml/kg) underestimated RBC loss in patients with large changes in hematocrit and over-estimated RBC loss in neonates where the circuit volume is greater than the patient blood volume. In non-bleeding patients, intravascular hemolysis represented 16% of total RBC loss and diagnostic phlebotomy 24%, suggesting that ~60% of RBC loss was due to other causes. REV generation was increased sevenfold to ninefold during ECMO.
RLI (ml/L/h) is a more reliable quantitative indicator of RBC loss than transfusion rate (ml/kg) for pediatric patients on ECMO. Phlebotomy and intravascular hemolysis only account for 40% of RBC loss in non-bleeding ECMO patients. High REV generation suggests sublethal damage and extravascular clearance may be a cause of RBC loss on ECMO.

Many patients with lower-risk myelodysplastic syndromes (LR MDS) require long-term red blood cell (RBC) transfusions to manage anemia. The consequences of RBC transfusions in LR MDS with ring sideroblasts (LR MDS-RS) are not well known. We estimated the association between cumulative RBC dose density and clinical and patient-reported outcomes using data from the MDS-CAN registry for patients enrolled between January 2008 and December 2018. Outcomes included overall survival, hospitalization, and health-related quality of life (HRQoL). A total of 145 enrolled patients with LR MDS and RS ≥5% had a median follow-up time of 27.1 months; 45 had no transfusions during follow-up, 51 had <1 transfusion per month, and 49 had ≥1 transfusion per month. The cumulative density of RBC transfusions was associated with significantly greater mortality, hospitalization, and inferior HRQoL, suggesting that exposure to RBC transfusion may constitute a significant treatment burden in patients with LR MDS-RS.

Neonatal anaemia is a very frequent clinical condition that may be due to apparent or not evident blood loss, decreased red blood cells (RBCs) production, or increased destruction of RBCs. RBCs transfusion criteria are clearly defined by several national and locally agreed guidelines. However, it is not possible to define a unique cut-off to guide clinicians\' transfusion practice, which needs a multiparametric analysis of demographic variables (gestational age, postnatal age, birth weight), clinical evaluation, conventional and new generation monitoring (such as echocardiography and near-infrared spectroscopy). Unfortunately, few tools are available in the delivery room to help neonatologists in the management of newborn with acute anaemia. Early volume replacement with cristalloids and RBCs transfusion could be life-saving in the delivery room when a hypovolaemic shock is suspected, but the use of un-crossmatched whole is not risk-free nor easily available in clinical practice. Placental transfusion could be an extremely effective and inexpensive method to increase haemoglobin (Hb), to improve oxygen delivery, and to increase cardiac output with a reduced need for RBCs transfusions, a reduced risk of intraventricular haemorrhages, and an improved survival of the newborn.

In this review paper, we examine the latest evidence regarding the use of iron supplementation, erythropoiesis-stimulating agents (ESAs), and blood transfusions as therapeutic targets for anemia to mitigate morbidity and mortality in patients with cardiovascular disease.
Intravenous ferric carboxymaltose (FC) injections in heart failure (HF) have resulted in improved self-reported patient symptoms; higher exercise capacity, as measured by 6-min walk test distance in anemic patients; and lower re-hospitalization rates in iron deficient patients. Darbepoetin alfa has shown evidence of improved Kansas City Cardiomyopathy Questionnaire scores. No mortality benefits have been noted thus far with FC injections or darbepoetin in HF, with an increase in adverse events with darbepoetin. Aggressive transfusions (Hg < 10 g/dL) are not associated with improved outcomes in cardiovascular disease. Quality of life metrics, rather than mortality, appear to improve with IV FC and ESA use in HF. More studies are required to see if these treatments have a role in coronary artery disease. Current evidence suggests that anemia is a marker of underlying disease severity, with a limited role in disease modification. Further studies are required to solidify our understanding of this topic.

BACKGROUND: Low red blood cell (RBC) levels are associated with worse intracerebral hemorrhage (ICH) outcomes. However, relationships of RBC transfusions on ICH outcomes are unclear given the overlap of RBC transfusion, comorbidities, and disease severity. We investigated RBC transfusion relationships on ICH outcomes while accounting for comorbidities and disease severity.
METHODS: ICH hospitalizations between 2002 and 2011 and RBC transfusion exposure were identified from the Nationwide Inpatient Sample using ICD-9-CM codes. Logistic regression was used to study the relationship between RBC transfusion on outcomes after adjusting for demographics, baseline comorbidities, and markers of disease severity. Additional sensitivity analyses stratified by comorbidity burden and disease severity were performed.
RESULTS: Of 597,046 ICH hospitalizations, RBC transfusions were administered in 22,904 (4%). RBC transfusion was associated with higher odds of in-hospital mortality (adjusted OR: 1.22 [95%CI: 1.10-1.35]). In sensitivity analyses, RBC transfusions resulted in poor outcomes regardless of the comorbidity burden, but attenuation in this relationship was notable with lower comorbidities (adjusted OR 1.43 [95%CI: 1.34-1.51] vs 1.18 [95%CI: 1.10-1.29]). There were no associations of RBC transfusions with poor outcomes in hospitalizations without mechanical ventilation (adjusted OR 0.88 [95%CI: 0.83-1.13]) and in cases requiring ventriculostomy drains (adjusted OR 1.05 [95%CI: 0.97-1.10]).
CONCLUSIONS: In a large, nationally representative sample, RBC transfusion was associated with poor ICH outcomes. However, there were variations in this relationship based on comorbidities and disease severity. Additional prospective studies are required to assess direct risks and benefits from RBC transfusions in ICH.