Red Cell Transfusion Research Articles

Mitapivat for Acquired Pyruvate Kinase Deficiency.

Pyruvate kinase (PK) activation is emerging as a promising treatment modality for numerous congenital hemolytic anemias of diverse pathophysiology, and one agent, mitapivat, is already licensed to treat patients with congenital PK deficiency. However, PK deficiency may also be acquired in the setting of clonal myeloid disorders and other pathologies, where it may result in severe hemolytic anemia and remains without known therapies. This case report describes the novel application of mitapivat therapy in a patient with acquired PK deficiency causing red cell transfusion dependence, liberating the patient from transfusions and resulting in marked improvement in symptoms and quality of life.

Prophylactic red cell transfusions for sickle cell disease pregnancy: increased use of therapy could transform outcomes.

Pregnancy for people with sickle cell disease (SCD) is high risk with persistently high rates of severe maternal and fetal mortality and morbidity. Transfusion therapy is the best-studied treatment for SCD in pregnancy; hydroxyurea is not usually used because of teratogenicity concerns. In high-resource settings, red cell transfusions are likely underutilized, while in low-resource settings, they may be altogether unavailable. A randomized controlled trial and meta-analysis, two of the strongest forms of clinical research, show transfusion significantly reduces maternal and fetal death, painful crisis, thrombosis, and acute respiratory failure. Downstream benefits of treatment are less well measured and may include improving maternal anemia, reducing opioid exposure, and avoiding hospitalization, which presents risk for additional complications. Alloimmunization is a particular transfusion risk in SCD. However, many strategies can mitigate this risk. Accordingly, the American Society of Hematology classifies chronic transfusion in pregnancy as low risk. Given the low risk classification, lack of alternative therapies, dismal, stagnant pregnancy outcomes and the potential for profound treatment benefit, wider use of chronic transfusion therapy for SCD pregnancy is likely indicated. This review discusses the benefits and potential risks of prophylactic transfusions for SCD pregnancy. Use of chronic transfusions during pregnancy is indicated to help urgently transform outcomes.

Effect of platelet storage duration on platelet increment and clinical outcomes in critically ill patients - a randomised controlled trial.

Platelet storage duration may influence transfusion effectiveness and patient outcomes.The present study aimed to evaluate the effect of platelet storage duration on platelet increment and clinical outcomes in patients admitted to the intensive care unit (ICU). This prospective, open-label, randomized controlled trial, conducted at a single centre, enrolled ICU patients requiring platelet transfusion. Patients were randomly assigned to receive platelet concentrates aged ≤3 days (Group 1) or 4-5 days (Group 2). Platelet increments were assessed by Absolute Platelet Count Increment (ACI), Corrected Count Increment (CCI), and Percentage Platelet Recovery (PPR). Clinical outcomes including bleeding, infection rates, ICU stay, red cell transfusion requirements, and mortality were also monitored. Patients transfused fresher platelets (Group 1) had higher median ACI, CCI and PPR at 1 hour compared to those transfused older platelets (Group 2) though the difference was not statistically significant.At 24 hours, Group 1 patients had a median ACI of 28,000/µl compared to 14,000/µl in Group 2(p = 0.001). The median CCI was 16,800 in Group 1 versus 8,200in Group 2(p = 0.001). Group 1 also had a higher median PPR of 45.7% compared to 23.6% in Group 2(p = 0.011).There was no significant difference in clinical outcomes such as bleeding, infection rates, ICU stay, or mortality between the groups. Multivariate analysis indicated that co-morbidities and higher APACHE-III score were associated with increased mortality. Transfusion of fresher platelets resulted in higher increments and transfusion effectiveness but did not affect clinical outcomes or mortality. Trial registration details: Clinical Trials Registry of India (CTRI/2023/03/050676).

Frequencies and causes of ABO-incompatible red cell transfusions in France, Germany and the United Kingdom.

Prevention of ABO-incompatible red cell transfusions (ABO-it) requires accurate donor and patient identification and correct application of processes for transfusion safety. In France and Germany, a bedside identity check and ABO compatibility test are performed. In the UK, an identity check, often structured as a bedside checklist, is performed with or without electronic patient identification (ePID). To compare the efficacy of ABO-it bedside preventive measures, frequencies and causes of ABO-it between 2013 and 2022 were investigated in all three countries. Despite differing bedside safety measures, similar average ABO-it frequencies were observed in France (0.19 [SD:0.09]/100 000 issued red cell units) and in the UK (0.28 [SD:0.17]/100 000), whereas a higher frequency (0.71 [SD:0.23]/100 000) was observed in Germany which has similar bedside safety measures to France. ABO-it resulted mostly from erroneous patient identification and transfusion of a red cell unit intended for another patient. In France and Germany, all ABO-it were associated with incorrectly performed identity check and ABO compatibility test. In the UK, most ABO-it were associated with incorrectly performed identity checks. Current measures to prevent ABO-it are not fully effective. Further development and implementation of effective patient identification systems, including electronic information systems, across the entire transfusion process, should be considered.

Spontaneous Renal Arteriovenous Malformation Presenting with Hematuria: A Case Report

Introduction: Rare vascular abnormalities called renal arteriovenous malformations (AVMs) can cause hematuria among other symptoms. Due to overlapping clinical and radiological symptoms, differentiating between renal AVMs and other disorders such renal cell carcinoma (RCC) can be difficult. Here, we report a case of a patient who developed hematuria and was first diagnosed with renal AVM. We go over the difficulties in diagnosing this ailment and the approaches to managing it. Case Presentation: A 34-year-old female patient, reported having hematuria with clots for one week, coupled with fever and left loin discomfort that persisted for four and one day, respectively. Her hemoglobin level was 4.5 g/dL at arrival, which required packed red cell transfusions. A left double-J stent was implanted after an emergency cystoscopy revealed bloody efflux from the left ureteric orifice. A potential arteriovenous malformation in the left kidney's upper pole area was discovered by further imaging. A cirsoid-type AV abnormality arising from the superior polar branch of the renal artery was verified by renal angiography. After therapeutic embolization, the patient's symptoms were relieved and hematuria stopped. Discussion: The case study highlights the need of taking renal AVMs into account when making a differential diagnosis for hematuria, especially if there haven't been any previous urological operations. It also emphasises how important imaging techniques like renal angiography and renal ultrasonography with Doppler are for making the right diagnosis. Distinctive diagnosis from other ailments, such as renal cell carcinoma, highlights the necessity of comprehensive assessment and monitoring to guarantee suitable treatment. Conclusion: Renal arteriovenous malformations are rare but important causes of hematuria. Prompt diagnosis and management are crucial to prevent complications and improve patient outcomes. This case report demonstrates the diagnostic challenges associated with renal AVMs and underscores the importance of a multidisciplinary approach in their evaluation and treatment.

Generalizability of SELECT to a contemporary cohort of cardiac surgical patients: analysis of the TRICS III Randomized Trial

Abstract Background The SELECT trial reported a significant reduction in cardiovascular (CV) outcomes with semaglutide amongst patients without diabetes who had pre-existing CV disease and a body-mass index (BMI) of 27 or greater. Patients undergoing cardiac surgery represent a high-risk subset of those with established CV disease, and may benefit from treatment with semaglutide. Purpose This study evaluated the generalizability of SELECT to a contemporary international cohort of cardiac surgical patients, and assessed whether differences between SELECT-eligible and non-eligible patients translated to altered risks of CV outcomes. Methods Present data was gathered from the TRICS III trial, a multicentre, randomized trial of restrictive versus liberal red-cell transfusion thresholds amongst 5243 cardiac surgical patients with a EuroSCORE I of ≥6. The proportion of cardiac surgical patients eligible for SELECT was determined by applying its selection criteria to the TRICS III cohort. Finally, baseline characteristics and outcomes stratified by SELECT eligibility were compared. Results A total of 4887 patients from the TRICS III cohort had available data for analysis, of which 452 (9.2%) were deemed to have been eligible for the SELECT trial. A comparison of baseline characteristics between SELECT-eligible and non-eligible patients are presented in Table 1; while SELECT-eligible patients were more likely to have preserved left ventricular function (71.7% vs. 61.0%), EuroSCORE I values were comparable between the two groups (7.8±2.1 vs. 7.9±1.9). The rate of a 3-point MACCE of Death, MI or stroke in the present cohort of SELECT-eligible patients undergoing cardiac surgery (16.6%) was numerically higher than those enrolled in SELECT receiving semaglutide (8.1%) or placebo (10.0%), despite the shorter follow-up (6 months vs. 39.8 months). Six month outcomes following cardiac surgery were similar regardless of SELECT eligibility (Figure 1); no difference in risk of outcomes was documented for the 3-point MACCE [SELECT Eligible vs. Non-eligible – 16.6% vs. 14.5%; OR 1.17 (0.9-1.53); P=0.24] and the TRICS III primary composite of Death, MI, Stroke, or New-Onset Renal Failure with Dialysis [17.0% vs. 17.0%; OR 1.0 (0.77-1.29); P=0.98]. There was a trend towards higher rates of MI at 6 months amongst SELECT-eligible patients, but this difference failed to reach statistical significance [8.5% vs. 6.3%; OR 2.0 (0.96-1.39); P=0.08). Conclusions In this large international cohort of contemporary cardiac surgical patients, nearly 10% would have met eligibility for SELECT. SELECT-eligible patients undergoing cardiac surgery in TRICS III had a numerically higher rate of MACCE than those enrolled in SELECT, highlighting the high risk nature of this patient subgroup. However, amongst SELECT-eligible and non-eligible patients undergoing cardiac surgery, no significant difference in CV outcomes was uncovered.

Red cell transfusion related toxic metals exposure for fetus and newborns: an under-recognized public health concern.

Red cell transfusion related toxic metals exposure for fetus and newborns: an under-recognized public health concern.

Red blood cell transfusion in a tertiary Haitian hospital’s emergency department: patient characteristics and availability challenges

BackgroundRed blood cell (RBC) transfusions are essential for many patients admitted to emergency departments (ED). However, accessibility to red cell transfusions is often limited, especially in low-income countries such as Haiti. This article aims to determine the proportion of patients requiring emergency transfusion, transfused patients’ characteristics, as well as the response rate and timeliness of blood product delivery for requests made.MethodsA retrospective study was conducted among all patients with RBC transfusion indications from January to June 2022 at the ED of Mirebalais Teaching Hospital. The parameters studied included transfusion indications, pre-transfusion hemoglobin levels, and delay from prescription to transfusion.ResultsDuring the study period, 3993 patients received treatment in the ED. The proportion of patients requiring RBCs was 7.69%, including 145 males and 117 females, with a median age of 43 [30–56] years. Only 21.7% of these patients received a transfusion. The average pre-transfusion hemoglobin level was 4.75 ± 1.68 g/dL. The most common transfusion’s indications were infection/sepsis (36.74%), trauma (23.48%), and cancer (21.57%). The median time delay from prescription to transfusion was 2.37 [0.97–4.93] days. The study identified significant associations between RBC transfusion probability and patient factors like hemoglobin levels, patient disposition, urgency of RBC request, and length of stay.ConclusionRBC transfusion requests are frequent in the ED of Mirebalais Teaching Hospital, with a relatively high transfusion delay. Further studies on the relevance of RBC requests and ways to reduce delay from prescription to transfusion would be beneficial to improve this situation.

Clinical correlates of cerebellar injury in preterm infants with surgical necrotizing enterocolitis.

The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

Plasma proteomes of acute myeloid leukemia patients treated with transfusions reveal signatures of inflammation and hemostatic dysregulation

BackgroundBone marrow aplasia is a common feature in acute myeloid leukemia (AML) patients during their remission induction treatment, and is associated with potential complications such as bleeding, infection and anemia. Frequent platelet and red cell transfusions are administered to prevent and treat these complications. However, platelet counts are poorly associated with bleeding events in this population. Therefore, plasma protein levels could add valuable insights to improve our understanding of the patient's health state. In this study, we aimed to delineate the plasma proteome, including inflammatory pathways, hemostatic and immune components, of AML patients during treatment with intensive transfusion support.MethodsWe employed unbiased mass spectrometry (MS)-based proteomics on longitudinal plasma samples from 10 AML patients during intensive-transfusion treatment phase with healthy individuals as baseline control.ResultsA total of 450 proteins were quantified in plasma samples from AML patients and healthy controls. Alteration in proteins levels were mainly observed for proteins involved in inflammation (e.g. SAA1 and CRP), and complement (e.g. C9 and MASP2) when comparing AML versus healthy individuals. Correlation analysis revealed additional affected protein dynamics, including proteins associated with coagulation cascade, endopeptidase inhibitors activity and lipoprotein remodeling.ConclusionThe plasma proteome from AML patients during intensive treatment shows a disbalance in inflammation, endopeptidase inhibitors activity, lipoprotein remodeling, coagulation and complement. These effects and potential associations with bleeding risk will be further studied in a bigger cohort.

The Effects of Calcium Gluconate Administration on Potassium Levels of Post Packed Red Cell (PRC) Transfusion Patients with More Than Three-Day-Stored Blood at RSUP Haji Adam Malik, Medan

Background: Blood transfusion is an important and routine medical treatment, especially in cases requiring surgeries such as trauma. One of the biochemical changes that occurs in PRC due to erythrocyte storage is an increase in potassium levels. Hyperkalemia is the most common complication of stored blood transfusion. Cardiac arrest has been widely reported in transfusion-associated hyperkalemia. Methods : This study used a pre-experimental study with a pretest-posttest group design to determine the effects of Ca gluconate administration on blood potassium levels in patients receiving packed red cell (PRC) transfusions with blood stored for > 3 days at RSUP Haji Adam Malik Medan. Results : The distribution of sample characteristics in this study showed a mean age of 46 ± 13.63. There were 7 (22.6%) male and 24 (77.4%) female patients, with a mean BMI of 23.28 ± 6.44. Based on the hemodynamic profile, the mean systolic BP was 105.87 ± 20.59, diastolic BP 70.41 ± 11.94, RR 23.06 ± 2.39 and MAP 83.31 ± 14.48. The mean value of potassium levels before an administration of Ca gluconate was 5.84 ± 0.89, while the mean value after the administration was 5.43 ± 0.90. There were no statistically significant changes in the potassium levels after the administration of Ca gluconate in any samples. Conclusions : There are effects of Ca gluconate administration on the potassium levels of post Packed red cell (PRC) transfusion patients with blood stored for > 3 days at RSUP Haji Adam Malik Medan.

Myoglobin saturation as an intracellular indicator for transfusion need in oncology patients.

This study aims to demonstrate the potential of myoglobin saturation as an indicator of oxygen delivery adequacy to help determine the need for red cell transfusion. Modern blood management approaches have been established to optimise use of red blood cells for transfusions in patients with anaemia. However, most approaches make recommendations to transfuse based on haemoglobin or haematocrit levels and do not directly address adequacy of oxygen delivery. Intracellular oxygen determined by myoglobin saturation directly measures oxygen delivery at the tissue level. A custom built spectrometer system with an optical fibre probe was used in this pilot study to measure muscle cell myoglobin saturation noninvasively from the first digital interosseous muscles in patients undergoing planned red blood cell transfusion. Patients were recruited from both the in-patient and out-patient oncology service at a major university medical centre. Measurements were made immediately before, immediately after, and 24 h following transfusion. Clinical data and tissue oxygen values from the Somanetics INVOS system were also collected. Myoglobin saturation, and thus cellular oxygen increased in some, but not all patients receiving a transfusion, and was most pronounced in patients who initially had low myoglobin saturation compared with the group as a whole. Clinical decisions to transfuse based on haemoglobin or haematocrit thresholds alone are likely insufficient to optimise use of red blood cell transfusions. The combination of haemoglobin or haematocrit with myoglobin saturation may optimally determine who will benefit physiologically from a transfusion.

Role of dithiothreitol in the resolution of pretransfusion immunohematology testing in patients receiving the anti-CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma

Abstract: INTRODUCTION: Daratumumab (Darzalex; Janssen-Cilag Pty Ltd), an anti-CD38 monoclonal antibody (MoAb), has demonstrated high efficacy in treating relapsed and refractory multiple myeloma (MM). It stands as the pioneering anti-CD38 MoAb approved by the US FDA (2015) and TGA Australia (2017). While targeting CD38 on myeloma cells, daratumumab poses a challenge in pretransfusion testing by inducing panreactivity in indirect antiglobulin tests (IATs) due to CD38 expression on red cells. This study investigates the role of dithiothreitol (DTT) in resolving pretransfusion immunohematology testing in patients treated with daratumumab for MM. MATERIALS AND METHODS: Pretransfusion samples from three hematological patients diagnosed with MM and receiving anti-CD38 drugs necessitating red cell transfusion were subjected to immunohematology serological testing. Clinicians provided patient information, including gender, age, transfusion history, and time between anti-CD38 MoAb infusion and sample collection. Tests included ABO/RhD typing, IAT, both polyspecific and monospecific direct antiglobulin test (DAT), antibody (Ab) screening, Ab identification, eluate preparation, and red cell crossmatch. Control tests were conducted by incubating patient samples at 37°C for 1 h. RESULTS: ABO/RhD typing remained unaffected, yet all samples exhibited panreactivity in IATs. Two samples showed positive DAT results but negative eluates. Treatment of reagent red blood cells (RBCs) with 0.2 M DTT effectively mitigated interference by anti-CD38 monoclonal antibodies, resulting in compatible red cell crossmatches. Notably, incubation of patient samples at 37°C for 1 h yielded identical results. CONCLUSION: Pretreatment of erythrocytes with DTT deactivated the CD38 antigen, eliminating reactivity with patient serum treated with daratumumab. DTT treatment of reagent RBCs emerges as an efficient and accessible strategy to counteract interference from anti-CD38 drugs in pretransfusion tests.

Catheters linked thrombosis in neonates: a single center observational study

BackgroundCentral venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors.MethodsThis observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study’s eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed.ResultsSeventeen patients with catheter’s thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs’ days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters’ days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013–32.836).ConclusionMany factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.

Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents

BackgroundVitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents. ObjectivesTo evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK. MethodsWe retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK. ResultsTwo hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024). ConclusionFII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

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.

Pure Red Cell Aplasia - Post Major ABO Incompatible Allogenic Stem Cell Transplantation Role of Ibrutinib

Pure Red Cell Aplasia (PRCA) is a well-recognized complication of Major ABO-incompatible allogeneic stem cell transplantation. It is featured by anemia, Reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy. The mechanism for PRCA is presumed to be the persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which probably interfere with the engraftment of donor erythroid cells. Several risk factors for PRCA have been reported, such as the presence of Anti-A Isoagglutininsbefore transplantation, reduced intensity conditioning, absence of Graft Versus Host Disease (GVHD), sibling donor and Cyclosporin A(CsA) as GVHD prophylaxis. PRCA is not a barrier to going ahead with Hematopoietic Stem Cell Transplantation (HSCT). There are many therapeutic options however few recover spontaneously, among the available options include high-dose steroids, Erythropoietin(EPO), Plasma exchange, Donor lymphocyte Infusion (DLI), treatment with Rituximab, Bortezomib, Daratumumab and tapering or discontinuation of immunosuppression. All these options have variable success in the literature ranging from 30% - 70%, Non-responders become red cell transfusion dependent and their quality of life is impaired. We are reporting a novel therapeutic option, Ibrutinib as an armamentarium in treating the PRCA post-HSCT, which works by blocking the Bruton Tyrosine Kinase (BTK) pathway thereby inhibiting the host B cell isoagglutinins production and good clinical response.

A Propensity-Matched Cohort Study of Intravenous Iron versus Red Cell Transfusions for Preoperative Iron-Deficiency Anemia.

While preoperative anemia is associated with adverse perioperative outcomes, the benefits of treatment with iron replacement versus red blood cell (RBC) transfusion remain uncertain. We used a national database to establish trends in preoperative iron-deficiency anemia (IDA) treatment and to test the hypothesis that treatment with preoperative iron may be superior to RBC transfusion. This study is a propensity-matched retrospective cohort analysis from 2003 to 2023 using TriNetX Research Network, which included surgical patients diagnosed with IDA within 3 months preoperatively. After matching for surgery type and comorbidities, we compared a cohort of patients with preoperative IDA who were treated with preoperative intravenous (IV) iron but not RBCs (n = 77,179), with a cohort receiving preoperative RBCs but not IV iron (n = 77,179). Propensity-score matching was performed for age, ethnicity, race, sex, overweight and obesity, type 2 diabetes, hyperlipidemia, essential hypertension, heart failure, chronic ischemic heart disease, neoplasms, hypothyroidism, chronic kidney disease, nicotine dependence, surgery type, and lab values from the day of surgery including ferritin, transferrin, and hemoglobin split into low (<7 g/dL), medium (7-<12 g/dL), and high (≥12 g/dL) to account for anemia severity. The primary outcome was 30-day postoperative mortality with the secondary outcomes being 30-day morbidity, postoperative hemoglobin level, and 30-day postoperative RBC transfusion. Compared with RBC transfusion, preoperative IV iron was associated with lower risk of postoperative mortality (n = 2550/77,179 [3.3%] vs n = 4042/77,179 [5.2%]; relative risk [RR], 0.63, 95% confidence interval [CI], 0.60-0.66), and a lower risk of postoperative composite morbidity (n = 14,174/77,179 [18.4%] vs n = 18,632/77,179 [24.1%]; RR, 0.76, 95% CI, 0.75-0.78) (both P = .001 after Bonferroni adjustment). Compared with RBC transfusion, IV iron was also associated with a higher hemoglobin in the 30-day postoperative period (10.1 ± 1.8 g/dL vs 9.4 ± 1.7 g/dL, P = .001 after Bonferroni adjustment) and a reduced incidence of postoperative RBC transfusion (n = 3773/77,179 [4.9%] vs n = 12,629/77,179 [16.4%]; RR, 0.30, 95% CI, 0.29-0.31). In a risk-adjusted analysis, preoperative IDA treatment with IV iron compared to RBC transfusion was associated with a reduction in 30-day postoperative mortality and morbidity, a higher 30-day postoperative hemoglobin level, and reduced postoperative RBC transfusion. This evidence represents a promising opportunity to improve patient outcomes and reduce blood transfusions and their associated risk and costs.

Predictors and pathways of in-hospital mortality in active vascular contrast extravasation detected on abdominopelvic CT

ObjectivesThis study aimed to identify factors influencing in-hospital mortality in adult patients with active vascular contrast extravasation (AVCE) on abdominopelvic computed tomography (CT).MethodsAll consecutive patients with AVCE detected on CT between January 2019 and May 2022 were retrospectively included. Their data were compared through uni- and multivariable analyses between patients with and without in-hospital mortality. Path analysis was utilized to clarify the relationships among factors affecting mortality.ResultsThere were 272 patients (60.2 ± 19.4 years, 150 men) included, of whom 70 experienced in-hospital mortality. Multivariable analysis revealed nonsurgery, chronic kidney disease (CKD) stage 4–5 or dialysis, prolonged partial thromboplastin time (PTT), minimum AVCE length > 8 mm, and a lower rate of packed red cell (PRC) transfusion were identified as independent predictors of in-hospital mortality (p = 0.005–0.048). Path analysis demonstrated direct influences of CKD4-5 or dialysis, prolonged PTT, and minimum AVCE length on mortality (coefficients 0.525–0.616; p = 0.009 to < 0.001). PRC transfusion impacted mortality through nonsurgery (coefficient 0.798, p = 0.003) and intensive care unit (ICU) admission (coefficients 0.025, p = 0.016), leading to subsequent death. Three AVCE spaces (free, loose, and tight) defined on CT were not directly associated with in-hospital mortality.ConclusionIn adults with AVCE on CT, AVCE size had a direct independent influence on mortality, highlighting the critical role of radiologists in detecting and characterizing this finding. Additionally, CKD4-5 or dialysis and prolonged PTT also directly influenced mortality, while the lower rate of PRC transfusion impacted mortality through nonsurgery and ICU admission.Clinical relevance statementIn patients with active vascular contrast extravasation (AVCE) on abdominopelvic CT, larger AVCE directly increased in-hospital mortality. Radiologists’ detection and characterization of this finding is crucial, along with recognizing factors like CKD4-5, dialysis, and prolonged PTT to improve patient outcomes.Key PointsSeveral factors independently predicted in-hospital mortality in patients with abdominopelvic AVCE.Extravasation length > 8 mm was the only imaging marker predictive of in-hospital mortality.Non-imaging factors correlated with in-hospital mortality, and PRC transfusion impacted mortality through nonsurgery and ICU admission pathways.Graphical

Perioperative Albumin Among Adults Undergoing Thoracic Surgery in the United States: Utilization, Associations With Clinical Outcomes, and Contribution to Hospital Costs

Objectives: To estimate the use of albumin among adults undergoing thoracic surgery in the United States, compare baseline characteristics, clinical and cost outcomes of recipients versus non-recipients, and determine albumin's contribution to total hospital costs. Design: Retrospective cohort study. Setting: Nationwide sample of US hospitals. Participants: Adults undergoing open and minimally invasive thoracic surgery between 2011 and 2017. Interventions: Albumin on the day of surgery (identified using itemized hospital billing logs). Measurements and Main Results: Albumin was used in 170 of 342 US hospitals, among 13% and 7% of 14672 and 22532 patients who respectively underwent open and minimally invasive thoracic surgery (median volume 500cc). Baseline comorbidities and organ supportive treatments were several-fold more prevalent among recipients (particularly vasopressors, mechanical ventilation, red cell transfusions). In standardized mortality ratio propensity score weighted analysis, albumin use was not associated with in-hospital mortality (adjusted RR 1.17 [0.72, 1.92] and 1.51 [0.97, 2.34], with open and minimally procedures), but was associated with morbidity and higher costs, more so with minimally invasive than open surgery. Total costs among recipients were higher by $4,744 [$3,591, $5,897] and $5,088 [$4,075, $6,100] for open and minimally invasive procedures respectively. Albumin accounted for 2.6% of this difference (median $124 [$83-$189] per patient). Conclusions: Albumin use varies widely across hospitals, and 9% of patients receive it (median 500cc). Use was not associated with in-hospital mortality and was associated with more morbidity and cost. The cost of albumin accounted for a trivial portion of hospital costs. Clinical trials must examine effects of albumin on complications and costs after thoracic surgery.