pRBC Units Research Articles

A 6-month Review of pRBC Transfusion Practices in a Tertiary Institution in Brooklyn, NY

Abstract Introduction/Objective Many factors are considered when managing hospital blood inventory. Because demographics and types of services vary per institution, a conscious effort to survey the prevalence of different blood types is necessary to make better predictions of inventory adequacy and decrease inappropriate use of O pRBC units. Methods/Case Report We reviewed the transfused pRBC units between October 2023 and March 2024 to determine the number of patients receiving ABO-type specific units and the number of D+ patients receiving D- units. Results (if a Case Study enter NA) After review, the patient population was found to be approximately 80% African Americans. Most of our patients were D+ with a monthly average of 224 patients. In contrast, we served 15 D- patients per month (PPM). Between 21-33% of D+ patients received D- units. O blood type was the most common, with an average of 224 PPM, followed by A blood type at 57 PPM and B blood type at 51 PPM. Since we see an average of 10 AB blood type patients monthly, it wasn’t surprising that they all received non-type specific units. Noteworthy is the significant proportion of A and B blood type patients receiving ABO type-specific units, ranging from 74-85% for A blood type and 70-90% for B blood type. Conclusion Our institution’s commitment to hemovigilance and conservation of O units is evident in the relatively high percentage of patients receiving ABO-type specific units. It is worth noting that we are a tertiary institution mainly serving the African American population. This creates a unique need to maintain adequate O units for emergency transfusion and increase the possibility of using O units to meet our sickle cell disease patients’ needs. Given that our demographics are primarily D+, some of our D- units were utilized in D+ patients. By adhering to our transfusion protocol and surveying our patients’ ABO and D blood types, we can anticipate our inventory needs and help prevent future O pRBC shortages.

Determination of Citrate Content of Commonly Transfused Blood Products

Abstract Background Citrate is a calcium-chelating anion used as an anticoagulant in the collection and manufacturing of blood products for transfusion. Overwhelming of normal hepatic catabolism of infused citrate, such as in liver failure or in massive transfusion, may cause citrate toxicity. Resultant hypocalcemia, impaired coagulation, and metabolic alkalosis results in increased patient mortality and morbidity. The citrate load per blood product unit is rarely known to the transfusionist, precluding precise calcium repletion. Manufacturing data of citrate content is available, but it is unreliable and often contradictory. The aim of this project is to directly measure the citrate concentrations of common blood products including packed red blood cells (pRBCs), plasma, and apheresis platelets. Methods Blood products (or samples thereof) were obtained, centrifuged, and assayed using a benchtop enzymatic citrate assay (Sigma-Aldrich). This technique generates a chromogenic product detectable via spectrophotometry at 570nm via conversion of citrate to a pyruvate intermediate. Blood products were serially diluted to the assay’s concentration measurement range based on estimations from the product manufacturing processes. Validation studies were performed to verify no significant interference from native pyruvate or from hemolysis at the dilutions used. All samples were run with a paired reference standard. Product type, storage duration, volume, and anticoagulant/preservative solution were recorded. Results Preliminary testing was performed on eleven pRBC units, twelve apheresis platelet units, and four whole blood(WB)-derived plasma. Measured citrate content of AS-1 and AS-5 units ranged from 43.56 - 114.5 mg while that of AS-3 units ranged from 327.23 – 816.82 mg, compared to manufacturing estimates of 188 mg and 883 mg, respectively. Measured citrate content of apheresis platelets ranged from 822-1533 mg compared to manufacturing estimates of 805 mg. Measured citrate content of WB-derived plasma also exceeded the manufacturing estimate of 1201 mg. Interference from pyruvate and hemolysis were insignificant at the dilutions used for testing. Validation of pRBC segment sampling is ongoing. Conclusion Varying guidelines exist for the correction of hypocalcemia during ongoing trauma resuscitation; however, guidance is limited regarding repletion by specific blood product. Our investigation affirms significant heterogeneity in pRBC citrate concentrations by collection method and identifies lower citrate concentrations than expected. This may be due to citrate metabolism by RBCs during storage. Platelet and FFP products contain significantly greater citrate masses by comparison, with a high degree of variation observed due to inherent product volume variability. Further sampling and testing are ongoing to establish reliable expected citrate loads for commonly transfused blood products.

6668 Myxedema Coma and Takotsubo Cardiomyopathy

Abstract Disclosure: A.M. Skariah: None. S. Jain: None. Background: Takotsubo cardiomyopathy (TCM) also know as broken heart syndrome is a transient decrease in systolic cardiac function in the absence of obstructive CAD. TCM is likely related to hyperadrenergic conditions leading to increased cardiac sensitivity to catecholamine surge leading to cardiomyopathy. TCM is more associated with hyperthyroidism. Case presentation: Patient is an 84-year-old female with PMH of celiac disease,hypertension,prediabetes, and atrial fibrillation s/p cardioversion, on amiodarone. She was brought to the ER after having an unwitnessed fall. She was hypotensive 76/56 mm of Hg, hypothermic 35.5 degree C, HR 90 beats/min; labs significant for hyponatremia, macrocytic anemia, TSH 65.47uIU/ml, FT4 <0.4 ng/dl and mild QTC prolongation of 469ms. Family mentioned history of constipation, progressive weakness, poor oral intake, memory problems and cold sensitivity for a couple of months. Started on 1 pressor, 3 units of PRBC and 2 liters of IVF; BP improved; labs and history suggestive of myxedema coma with myxedema coma Popoveniuc score 85 suggestive of high suspicion for myxedema coma.She had TSH 50.39 uIU/ml and FT4 of 0.4 ng/dl for her memory issues workup 2 months prior to presentation but was not started on medication. Upon admission, started stress dose steroids followed by IV levothyroxine 100 mcg. Not started on LT3 given her old age and atrial fibrillation history. Received additional dose of LT4 100 mcg within few hours. TFT improved with TSH 35 uIU/ml and FT4 1 ng/dl after 2 doses. Later same day, shock worsened, and patient was on 3 pressors along with stress dose of steroids. Cardiology was consulted; recommended an Echocardiogram.Echo was done on day 2; EF 55-60 % with severe hypokinesis of apical myocardium consistent with TCM. Normal echocardiogram studies 4 months ago.Started on weight-based regimen of LT4 75 mcg IV on day 3 and switched to 100 mcg oral when patient tolerated pills.Patient was down to 2 pressors on day 3 and gradually off pressors by day 6. Repeat TFT -showed improvement TSH 12 uIU/ml and FT4 0.7 ng/dl—day 5. Eventually her mentation improved and was discharged on oral LT4. Conclusion: TCM is rare complication of treatment of myxedema coma. Our patient developed shock requiring 1 pressor which unexpectedly worsened to 3 pressors requirement after initial LT4 treatment. High doses of LT4 and LT3 which is part of myxedema coma treatment sensitizes myocardial tissue to catecholamines by increasing expression of beta adrenoreceptors in cardiac myocytes with subsequent ionotropic and chronotropic effects. This may contribute to cardiac stunning and TCM. It’s beneficial to evaluate patients with myxedema coma who develop worsening cardiac status after initiation of high dose of thyroid hormone replacement for TCM. Presentation: 6/2/2024

A-114 Protective effect of leukocytes in preventing Cold Induced Hyperkalemia

Abstract Background Cellular components, especially PRBC units stored in blood banks show progressively increasing extracellular potassium because ATP dependent Na+/ K+ATPase that pumps potassium into cells is slowed at cold but K+ leak continues. The extracellular potassium levels in these units may go well above the range of linearity of some electrolyte analyzers and may need dilution to measure accurately. We wanted to see effect of Leukocytes on this progressive cold-storage hyperkalemia. Buffy-Coat, the leukocyte rich layer of spun whole blood, a discard product of blood banks using buffy-coat-method for components, was used as the source of leukocytes. Methods Buffy-Coat-bags (from Terumo Quadruple-bag-set, in CPD) were separated from 32 donations from male donors (with IRB, consent). Eight ABO,Rh compatible pools of four buffy each, were prepared and divided into 2 groups of four pools each:Leukoreduced pools (LR group): Each pool leukoreduced by a clinical-grade commercial Leukofilter (Mitra).Non-leukoreduced pools (NLR group) rich in leukocytes. Potassium/VBG on Cobas B221(Roche), and CBC were done on days 0, 3, 7 on each pool stored at 4oC. Results Potassium was significantly lower in NLR than LR pools on days 3 & 7, and potassium had significant negative correlation with WBC count. Multiple-linear-regression and analysis of additional control experiments consistently showed that independent of days of storage, pH, and Hct, WBC-Count had significant negative correlation with Potassium. Conclusions Preanalytic artefacts like “seasonal-pseudohypokalemia” and pseudohypokalemia in a subset of AMLs (opposite of pseudohyperkalemia in fragile hyperleukocytosis) suggest that leukocytes may be capable of reducing extracellular potassium. Our in-vitro closed-system controlled experiments show that leukocyte-rich/Non-Leuko-Reduced (NLR) pools were relatively protected from hyperkaleimia than filtered leukocyte-poor/Leuko-Reduced (LR) buffy pools, and potassium has significant negative correlation with leukocyte count independent of storage-time, pH & Hct. Though considered otherwise bad/aggravator for “PRBC-storage-lesion”, leukocytes may help abate progressive cold-storage-hyperkalemia.

Acid–base and electrolyte changes in dogs after packed red blood cell transfusion

AbstractBackgroundPacked RBC (pRBC) transfusions are often necessary to enhance organ perfusion and tissue oxygenation in cases of severe anemia.ObjectivesWe aimed to describe changes in acid–base and biochemical parameters in dogs after transfusion of pRBC and potential effects on the outcome.MethodsThe prospective observational study included anemic dogs requiring pRBC transfusions. Venous blood gas and electrolytes were measured pre‐transfusion and repeated within 1 h post‐transfusion. Signalment, pre‐existing conditions and underlying disease(s), number of days spent of hospitalization, the quantity of transfused pRBC units, and the outcome were also recorded. Associations between analytical values and all other parameters before and after transfusion were assessed using the Wilcoxon test. A generalized linear model was generated for each of the blood gas parameters post‐transfusion, including the pre‐transfusion values and the characteristics of the animal as fixed effects. The effect of the blood gas parameters on the mortality and hospitalization length was assessed using logistic regression and generalized linear models, respectively.ResultsTwenty‐six dogs with different causes of anemia were included in the study, with dogs remaining hospitalized for a median of 3 days (range: 0–11). Pre‐transfusion heart rate, respiratory rate, Angap, base excess, and lactate were higher than post‐transfusion values. Post‐transfusion results showed an increase in hematocrit, hemoglobin, HCO3‐, PCO2, tCO2, and chloride. Pre‐transfusion hypophosphatemia and receiving an increased volume of transfused pRBC were associated with a longer hospital stay, while higher pre‐transfusion lactate values were associated with higher mortality.ConclusionspRBC transfusion in anemic dogs was associated with an improvement in perfusion and acid–base parameters. Pre‐transfusion lactate may be an indicator of mortality in dogs.

Effects of red blood cell transfusion on patients undergoing cardiac surgery in Queensland – a retrospective cohort study

BackgroundPacked red blood cell (pRBC) transfusion is a relatively safe and mainstay treatment commonly used in cardiac surgical patients. However, there is limited evidence on clinical effects of transfusing blood nearing end-of shelf life that has undergone biochemical changes during storage.ObjectiveTo investigate evidence of associations between morbidity/mortality and transfusion of blood near end of shelf-life (> 35 days) in cardiac surgical patients.MethodsData from the Queensland Health Admitted Patient Data Collection database 2007–2013 was retrospectively analysed. Coronary artery bypass graft and valvular repair patients were included. Multivariable logistic regression was used to examine the effect of pRBC age (< 35 days vs. ≥ 35 days) on in-hospital mortality and morbidity. As secondary analysis, outcomes associated with the number of pRBC units transfused (≤ 4 units vs. ≥ 5 units) were also assessed.ResultsA total of 4514 cardiac surgery patients received pRBC transfusion. Of these, 292 (6.5%) received pRBCs ≥ 35 days. No difference in in-hospital mortality or frequency of complications was observed. Transfusion of ≥ 5 units of pRBCs compared to the ≤ 4 units was associated with higher rates of in-hospital mortality (5.6% vs. 1.3%), acute renal failure (17.6% vs. 8%), infection (10% vs. 3.4%), and acute myocardial infarction (9.2% vs. 4.3%). Infection carried an odds ratio of 1.37 between groups (CI = 0.9–2.09; p = 0.14) and stroke/neurological complications, 1.59 (CI = 0.96–2.63; p = 0.07).ConclusionIn cardiac surgery patients, transfusion of pRBCs closer to end of shelf-life was not shown to be associated with significantly increased mortality or morbidity. Dose-dependent differences in adverse outcomes (particularly where units transfused were > 4) were supported.

Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial.

In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment.

FINDING THE SWEET SPOT: THE ASSOCIATION BETWEEN WHOLE BLOOD TO RED BLOOD CELLS RATIO AND OUTCOMES OF HEMORRHAGING CIVILIAN TRAUMA PATIENTS.

Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients.

Factor Eight Inhibitor Bypassing Activity as First-line Therapy for Coagulopathy in Cardiac Surgery

ObjectiveTo compare the outcomes of Factor Eight Inhibitor Bypassing Activity (FEIBA) versus Fresh Frozen Plasma (FFP) as the primary treatment for postoperative coagulopathy in cardiac surgery patients. DesignA retrospective, propensity-matched study. SettingA single, tertiary hospital. ParticipantsPatients who underwent non-coronary open-heart surgery with cardiopulmonary bypass between 2015 and 2023. InterventionsNone. Measurements and Main ResultsWe stratified patients into two groups based on whether they received intraoperative FFP or FEIBA, while cases using both were excluded. We analyzed 434 cases, with 197 receiving FFP and 237 receiving FEIBA. After propensity-matching, there was no significant difference in the proportion of the patients who required pRBC transfusions (p=0.08). However, of those who required pRBC transfusions, patients in the FEIBA group required significantly less units of pRBC (p<0.001). Significantly less patients in the FEIBA group required platelet (p<0.001) and cryoprecipitate (p<0.001) transfusions. The FEIBA group showed reduced prolonged postoperative intubation (p=0.05), reduced ICU length of stay (p=0.04), and lower 30-day readmission rates (p=0.03). There were no differences in rates of thrombotic complications between the two cohorts. ConclusionsIn the initial treatment of post-cardiopulmonary bypass coagulopathy, FEIBA may be more effective than FFP in reducing blood product transfusions and readmission rates. Further studies are needed to explore the potential routine use of FEIBA as first line agent in this patient population.

Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study.

Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC. We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior. Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA. PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. Therapeutic/Care Management; Level III.

Reconsidering Fresh Frozen Plasma Availability to Reduce Blood Product Waste During Massive Transfusion Events in Trauma.

Within component therapy of massive transfusion protocol (MTP) in trauma, thawed plasma is particularly susceptible to expiring without use given its short 5-day shelf life. Optimizing the number of thawed products without compromising safety is important for hospital resource management. The goal is to examine thawed plasma utilization rates in trauma MTP events and optimize the MTP cooler content at our Level I trauma center. Trauma MTP activations from 01/2019 to 12/2022 were retrospectively reviewed. During the study period, blood products were distributed in a 12:12:1 ratio of packed red blood cells (pRBC): plasma: platelets per cooler, with up to 4 additional units of low-titer, group O whole blood (LTOWB) available. The primary measure was percent return of unused, thawed plasma. There were 367 trauma MTP activations with a median (IQR) activation call-to-first cooler delivery time of 8 (6-10) minutes. 73.0% of thawed plasma was returned to the blood bank unused. In one third of MTP activations, all dispensed plasma was returned. The majority (74.1%) of patients required 6 or fewer units of plasma. In 81.5% of activations, 10 or fewer units of plasma and 10 or fewer units of pRBC were used. The majority of trauma MTP requirements may be accommodated with a reduced cooler content of 6 units pRBC, 6 units plasma, and 1 pheresis platelets, buffered by up to 4 units LTOWB (approximates 4 units of pRBC/4 units plasma), in conjunction with a sub-10min cooler delivery time. Follow-up longitudinal studies are needed.

Effect of leukoreduction on the omics phenotypes of canine packed red blood cells during refrigerated storage.

Red blood cell (RBC) storage promotes biochemical and morphological alterations, collectively referred to as storage lesions (SLs). Studies in humans have identified leukoreduction (LR) as a critical processing step that mitigates SLs. To date no study has evaluated the impact of LR on metabolic SLs in canine blood units using omics technologies. Compare the lipid and metabolic profiles of canine packed RBC (pRBC) units as a function of LR in fresh and stored refrigerated (up to 42 days) units. Packed RBC units were obtained from 8 donor dogs enrolled at 2 different Italian veterinary blood banks. Observational study. A volume of 450 mL of whole blood was collected using Citrate-Phosphate-Dextrose-Saline-Adenine-Glucose-Mannitol (CPD-SAGM) transfusion bags with a LR filter to produce 2 pRBC units for each donor, without (nLR-pRBC) and with (LR-pRBC) LR. Units were stored in the blood bank at 4 ± 2°C. Sterile weekly samples were obtained from each unit for omics analyses. A significant effect of LR on fresh and stored RBC metabolic phenotypes was observed. The nLR-pRBC were characterized by higher concentrations of free short and medium-chain fatty acids, carboxylic acids (pyruvate, lactate), and amino acids (arginine, cystine). The LR-pRBC had higher concentrations of glycolytic metabolites, high energy phosphate compounds (adenosine triphosphate [ATP]), and antioxidant metabolites (pentose phosphate, total glutathione). Leukoreduction decreases the metabolic SLs of canine pRBC by preserving energy metabolism and preventing oxidative lesions.

O blood type is not associated with worse coagulopathy or outcome in exsanguinating trauma

BackgroundDespite improving understanding of trauma-induced coagulopathy (TIC), mortality and morbidity due to exsanguinating trauma remain high. Increased complications due to hemorrhage have been reported in blood group O, possibly due to reduced levels of von Willebrand factor (vWF). MethodsAn urban level 1 adult trauma center registry was retrospectively queried. Patients receiving ≥6 units of pRBC within 4 ​h of presentation were included. Patient demographics, admission labs and outcomes were obtained. Univariate and multiple logistic regression analyses were performed. Results562 patients were identified. There were no significant differences in demographics, admission labs, or outcome between different ABO groups. After adjustment, Type A patients were more likely to be hypocoagulable compared to Type O patients (p ​= ​0.014). No mortality differences were seen between ABO types in multiple regression analysis. ConclusionsNo outcome or mortality differences were seen between ABO types, therefore factors other than vWF expression should be considered to explain coagulopathy in trauma patients.

The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials.

Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock. We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325. Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20). Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups. Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.

Efficacy and Safety of Roxadustat for Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndrome (LR-MDS) with Low Red Blood Cell (RBC) Transfusion Burden: Results of Phase III Matterhorn Study

Presented on behalf of all MATTERHORN (FGCL-4592-082) study investigators Introduction: For patients (pts) with LR-MDS, anemia poses a major clinical challenge, with limited response to first-line erythropoietin (EPO)-stimulating agents (ESAs) and a median duration of response ≤2 years. Further, pts with RBC transfusion dependence (≥2 packed RBC [pRBC] units every 8 weeks [Q8W]) are less likely to respond to ESAs. Anemia treatments with novel mechanisms of action enabling transfusion independence (TI) are needed to reduce frequent RBC transfusion burden. Roxadustat is a first-in-class, hypoxia-inducible factor prolyl hydroxylase inhibitor for treatment of anemia with chronic kidney disease. In the MATTERHORN (NCT03263091) dose-selection stage, roxadustat was well-tolerated, and 37.5% of pts (9/24) with LR-MDS and low RBC transfusion burden ([LTB] 1 pRBC unit Q8W for two consecutive 8-week periods or 2-4 pRBC units Q8W) achieved TI. In the MATTERHORN double-blind stage, TI response rate and safety of roxadustat were further assessed. Methods: MATTERHORN is an ongoing, double-blind, Phase III, randomized, placebo (PBO)-controlled trial. Eligible adult pts (≥18 years of age) had very low-, low-, or intermediate-risk primary MDS per Revised International Prognostic Scoring System (IPSS-R) classification (&amp;lt;5% bone marrow blasts); hemoglobin (Hb) ≤10.0 g/dL at baseline (BL); and LTB. Prior ESA use (&amp;gt;8 weeks before randomization) was permitted. Pts were randomized 3:2 to roxadustat or PBO, then stratified by serum EPO concentration (≤200 or 200-400 mIU/mL), IPSS-R risk, and transfusion burden. Pts received oral roxadustat (starting dosage: 2.5 mg/kg three times weekly based on the dose-selection stage) or PBO with best supportive care (BSC; per institutional criteria, including RBC transfusion) for a 52-week treatment period, followed by a 4-week follow-up period. Primary efficacy endpoint was percentage of pts with TI (the absence of RBC transfusion) for ≥56 consecutive days during the first 28 treatment weeks (TI responder). The percentage of pts with TI and mean Hb increase of ≥1.0 and ≥1.5 g/dL (averaged over 8 weeks) compared with BL pretransfusion Hb was also assessed (to be reported separately). Safety (including treatment-emergent adverse events [TEAEs] and serious TEAEs) was evaluated throughout the study. Results: As of the final 28-week interim analysis of the double-blind stage (data cutoff: April 24, 2023), 140 pts (82 roxadustat, 58 PBO) were randomized and treated. Across arms, median age was 71.5 years (range, 26-96), 59.3% (83/140) were male, and 80.0% (112/140) were white. Most pts (72.1% [101/140]) had IPSS-R low-risk disease and a transfusion burden of 2-4 pRBC units Q8W (92.1% [129/140]). Median (range) BL transfusion burden was 2.5 (1-10) pRBC units. Seventy pts (50.0%) received prior ESAs (98.6% [69/70] were ESA-refractory). Eighty-four pts (41/82 [50.0%] roxadustat, 43/58 [74.1%] PBO) completed 28 weeks of treatment, and 15 pts (6/82 [7.3%] roxadustat, 9/58 [15.5%] PBO) were continuing treatment. Median (range) treatment duration was 24.1 (1.1-28.0) weeks for the roxadustat arm and 28.0 (0.1-28.0) weeks for the PBO arm. A greater percentage of pts in the roxadustat arm compared with the PBO arm were TI responders (47.5% vs. 33.3%). However, this difference did not reach statistical significance ( p=0.22; figure). Percentages of pts with TEAEs of any grade, serious TEAEs, and TEAEs leading to treatment discontinuation were similar across arms (table). Six deaths occurred on study (roxadustat: pneumonia [n=2], acute myocardial infarction and ischemic stroke [n=1], multiorgan failure [n=1]; PBO: urosepsis [n=1], disease progression [n=1]). Three pts (all in roxadustat arm) progressed to acute myeloid leukemia. The study was terminated by the sponsor and is currently being completed. Conclusions: Despite not meeting the primary endpoint, roxadustat plus BSC was well-tolerated, and a high percentage of pts with LR-MDS and LTB were TI responders. The high TI response rate in the PBO arm, historically poor outcomes in pts with ESA-refractory disease, and the inclusion of pts who were not transfusion-dependent (1 pRBC unit Q8W) may have contributed to the lack of a statistically significant difference in TI response rates between arms. MATTERHORN outcomes highlight the continued unmet need for effective and safe therapies that reduce RBC transfusion burden in LR-MDS.

A Phase I/II, Intra-Patient Dose-Escalation Study of Bitopertin, a Selective Inhibitor of GlyT1 and Heme Synthesis, for Steroid-Refractory Diamond-Blackfan Anemia

Background: Diamond-Blackfan anemia (DBA) is a heritable bone marrow failure disorder characterized by macrocytic anemia with reticulocytopenia and bone marrow erythroid hypoplasia, usually presenting within the first two years of life. Treatment consists of systemic corticosteroids. Treatment failure or steroid intolerance occurs in approximately half of all cases, necessitating chronic transfusions, which carry the risks of iron overload and infections. Hematopoietic cell transplant remains the sole curative therapy for DBA. In cases where a causative mutation can be identified, with rare exceptions, the affected genes encode ribosomal proteins (RPs), defining DBA as prototypic haploinsufficient ribosomopathy. Erythrocyte hemoglobinization requires balanced heme synthesis and globin translation. Various in vitro and animal models suggest that RP insufficiency results in reduced ribosomal biogenesis, disrupting this balance and leading to excess of heme, resulting in toxicity to developing erythroid cells and premature termination of erythroid differentiation. Bitopertin is an investigational, orally administered, inhibitor of the GlyT1 glycine transporter. Outside the central nervous system (CNS), GlyT1 is expressed almost exclusively on developing erythrocytes. By reducing intracellular glycine, a rate-limiting substrate for heme synthesis, bitopertin slows heme synthesis and thus we hypothesize rebalances hemoglobin synthesis. In preclinical DBA models, bitopertin rescues erythropoiesis. The drug was originally developed for CNS indications, and has been shown to exhibit a favorable safety profile in prior studies with cumulative enrollment of over 4,000 patients and healthy volunteers. It is currently under clinical investigation for the treatment of erythropoietic protoporphyria. Study Design and Methods: This is a phase I/II, intra-patient dose-escalation study of bitopertin for steroid-refractory DBA, conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland. Subjects visit the NIH for initial evaluation and eligibility assessment and at the primary endpoint, with interim follow-up conducted via telehealth and local laboratory assessments. Subjects must be 18 years of age or and older, diagnosed with DBA and with clinically significant anemia (hemoglobin &amp;lt; 9/dL and/or requiring 2 units PRBC per 8 weeks). They must have relapsed and/or steroid refractory disease or be intolerant of systemic steroids, and be without significant comorbidities. Ongoing transfusions and chelation therapy are allowed, but other DBA-directed therapy, most notably steroids and growth factors, are not. Each subject will take oral bitopertin daily, escalating the dose monthly (5 mg, 10 mg, 20 mg, 40mg, and 60 mg) until reaching either the study maximum dose of 60 mg, the minimum effective dose (MED), or the maximum tolerated dose (MTD). Subjects will be followed for 8 months (32 weeks), including a minimum of 4 months (16 weeks) at the final dose (MED, MTD or study maximum). Response will be assessed on an ongoing basis and will be defined as an increase in hemoglobin ≥by 1.5 g/dL and/or a reduction in the units of PRBC transfusions by ≥50% from baseline. Furthermore, a robust response will be defined as a hemoglobin ≥10 g/dL and transfusion independence for 8 weeks. Patients with response (robust or non) by the 8-month primary endpoint will be allowed to continue extended therapy for 3 additional years. The primary endpoint is erythroid response. Secondary endpoints include safety as defined by the toxicity profile over 8 months of therapy and on extended therapy, relapse, survival, clonal evolution, health-related quality of life, and ancillary laboratory studies including the impact of bitopertin upon erythroid cell dynamics. The study employs a minmax design. A minimum of 15 patients will be enrolled. If the minimum efficacy threshold is met or surpassed (≥13% response rate), an additional 10 patients will be enrolled. Status: This study has been granted an FDA IND (165778) and is open for enrollment. It is monitored under the NIH Institutional Review Board (001528-H) and is registered with the U.S. National Library of Medicine (NCT05828108). Funding: This study is supported by the NHLBI Division of Intramural Research and in part through a Cooperative Research and Development Agreement (CRADA) with Disc Medicine, Inc. (Watertown, MA).

Retrospective Study of Blood Transfusion Utilization in Surgical Patients in a Quebec, Canada Health Region: Do We Overestimate the Surgical Risk

Introduction Blood transfusions were initially developed in the 20 th century to support emergency surgery on injured soldiers. Their access and use have since revolutionized our ability to perform elective surgeries. However, there is a misconception that surgical procedures continue to be a primary user of blood transfusions, such that many surgeons have become reliant on blood units being reserved for their patients. A high-risk surgery is currently defined as a 48-hour risk of requiring a transfusion in at least 2-4% of cases ( Blood 2012,120:2954-2963). Patients meeting that risk category must have a blood group determination and cross-match before elective surgeries. While data from the ACS-NSQIP US database reported a decrease from 5.5% to 4% in transfusion rate for general surgery procedures between 2012 and 2018, rates remain elevated, included a risk of 6.6% for hemorrhoid ligation ( Transfusion 2021,61:3119-3128). The present study sought to evaluate the rates of use of transfusions during and immediately following surgery in a Canadian setting. Given improvement in surgical techniques, the regulated training of surgeons, and a universal healthcare access favoring the concentration of more complex surgical cases to regional centers, it was suspected that the need for blood products may be overestimated. Study design We conducted a retrospective study of the use of pRBC transfusions in all surgeries performed during a 24-month period in a single Quebec health region. Region 12 has a mix of urban and rural communities with a total population of almost half a million inhabitants. All types of surgeries are performed, with the exception of cardiac surgery, neurosurgery, and transplantation. The region includes 5 operating theaters, a larger regional center with 8 operating rooms and 4 smaller centers with 2-5 rooms. The current recommendation is for all patients undergoing surgery to have a group determination and cross-match before all major surgeries. Results Between January 2018 to December 2019, a total of 34 934 elective and emergency surgeries were performed. 172 patients received a total of 546 pRBC units (0.49% of surgeries). 395 units were transfused either during surgery or during the first 24 hours post-operatively. During the same period, a total of 10 982 blood units were transfused in the health region for all indications. Only 4.9% were given to surgical patients. Table 1 demonstrates transfusion rates by surgical specialty in Health Region 12. Major surgeries such as thoracic and vascular surgery, and urologic and ENT oncology are centralized to the urban regional center. 9% of vascular surgeries required blood transfusions (half being elective procedures), followed by thoracic surgery with 2.8% of surgeries (half also being elective procedures). All other types of surgeries had a &amp;lt; 1% utilization of blood transfusion, independent of hospital. 34 cases (0.1%) required 3 or more blood units during surgery. Only 3 of 9 patients who received more than 5 blood units during the first 24 hours of surgery survived 30 days post-operatively. Of the 172 patients who were transfused, alloantibodies were found in only 7 patients, of which 4 were significant. All four were already known in the national database, even though two were not detected during the pre-operative cross-match. Conclusions The 48-hour surgical blood transfusion risk in our region is significantly lower than that reported in recent data. Surgical sub-specialization and the concentration of more complex cases in higher volume centers may explain the reduced operative blood transfusion risk. In the present study, only vascular and thoracic surgeries qualified as high-risk, representing only 1.4% of all surgeries performed in the region. Therefore, pre-operative complete cross-matching could be avoided in more than 98% of surgeries, resulting in significant savings in specialized technical time, which is of particular importance at a time of personnel shortages.

Trauma Laparotomy for the Cirrhotic Patient: An Outcome-Based Analysis

IntroductionThere is a lack of large-scale data on outcomes of cirrhotic patients undergoing trauma laparotomy. We aimed to compare outcomes of cirrhotic versus noncirrhotic trauma patients undergoing laparotomy. MethodsWe analyzed 2018 American College of Surgeons Trauma Quality Improvement Program. We included blunt trauma patients (≥18 y) who underwent a laparotomy. Patients who were transferred, dead on arrival, or had penetrating injuries were excluded. Patients were matched in a 1:2 ratio (cirrhotic and noncirrhotic). Outcomes included mortality, complications, failure to rescue, transfusion requirements, and hospital and intensive care unit (ICU) lengths of stay. Multivariable backward stepwise regression analysis was performed. ResultsFour hundred and seventy-one patients (cirrhotic, 157; noncirrhotic, 314) were matched. Mean age was 57 ± 15 y, 78% were male, and median injury severity score was 24. Cirrhotic patients had higher rates of mortality (60% versus 30%, P value <0.001), complications (49% versus 37%; P value = 0.01), failure to rescue (66% versus 36%, P value<0.001), and pRBC (units, median, 11 [7-18] versus 7 [4-11], P value <0.001) transfusion requirements. There were no significant differences in hospital and intensive care unit (ICU) lengths of stay (P value ≥0.05). On multivariate analysis, increasing age (adjusted odds ratio [aOR] 1.02, P value <0.001), Glasgow Coma Scale score ≤8 at presentation (aOR 3.3, P value <0.001), and total splenectomy (aOR 5.7, P value <0.001) were associated with higher odds of mortality. Platelet transfusion was associated with lower odds of mortality (aOR 0.84, P value = 0.044). ConclusionsOn a national scale, mortality following trauma laparotomy is twice as high for cirrhotic patients compared to noncirrhotic patients with higher rates of major complications and failure to rescue. Our finding of a protective effect of platelet transfusion may be explained by the platelet dysfunction associated with cirrhosis. Liver cirrhosis among trauma patients warrants heightened surveillance.

Evaluation of leukocyte depletion of packed red blood cell units and impact on clinically observed transfusion reactions.

The aim of this retrospective study was to determine whether there is an association between leukoreduction of packed red blood cell (pRBC) units and reduction of clinically observed transfusion reactions (TR), particularly febrile non-haemolytic transfusion reactions (FNHTR), and better outcomes in dogs. Secondary aims were to evaluate the effects of other factors suspected to influence transfusion reaction frequency or survival, including crossmatching, use of immunosuppressive drugs, and age and number of the blood products being administered. Medical data on dogs transfused with leukocyte-reduced (LR) and non-leukocyte-reduced (N-LR) pRBC units at the Animal Hospital Zürich, University of Zürich, Switzerland between January 1, 2007, and December 17, 2018 were searched. Before 2014, only N-LR blood were transfused. After 2014, both LR and N-LR blood were available. A total of 339 canine patients were transfused with 413 pRBC units; 30.5% (126/413) were LR units and 69.5% (287/413) were N-LR. Data collected from medical records was analyzed using univariate and multivariate logistic regression. In the present study, TR occurred in 19.8% of pRBC units (25/126) with LR and in 17.7% (51/287) of pRBC with N-LR; p > 0.05. FNHTR occurred in 6.3% of pRBC units (8/126) with LR and in 4.5% (13/287) of those with N-LR; p > 0.05. There was no correlation between the occurrence of TR and discharge from hospital (p > 0.05). Crossmatching, immunosuppressive therapy, and age of the blood product were not associated with the frequency of TR; p > 0.05 for all. The duration of survival days was not related to the number of transfusions dogs received. In the present study, the leukocyte-depletion of transfused pRBC units was not associated with fewer TR nor to fewer FNHTR compared to N-LR units. Discharge of dogs from hospital was not dependent on the occurrence of TR.

Fast Track Liver Transplantation: Lessons learned after 10 years running a prospective cohort study with an ERAS-like protocol

Fast Tracking in Liver Transplantation has been around for the past 25 years, although no substantial advancement, in the form of a comprehensive protocol, had been readily available. Few centers had embraced this goal, so before we started our program, a little over a decade ago, we adopted most of these ideas into a comprehensive pathway that would swiftly carry our patients from the preoperative stage through a safe home discharge. From day one, we have used this Fast Track pathway and applied it prospectively to every single patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our results after 10 years. Patients and MethodsAll liver transplants performed at our center for the first 10 years since the start of the program (September 2012–September 2022) were included. Our standard protocol included balanced general anesthesia, fluid restriction, avoidance of transfusions, inferior vena cava preservation with temporary porto-caval shunt and thromboelastography. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early. Results385 transplants were performed in 367 patients (287♂/80♀) over 120 months, mean age 57.4±9.5 years, raw MELD score 15.4±8.1. Predominant etiologies were alcohol (n=217) and HCV (n=108), with hepatocellular carcinoma present in 197 (53.7%). Eighteen patients underwent combined liver-and-kidney transplants. Mean operating time was 313±66 min with cold ischemia times of 281±85 min. Fifty-nine patients (15.3%) were transfused in the OR (2.3±1.1 units of PRBC). Extubation was immediate (< 30 min) in 365 cases (94.8%). Median ICU length of stay was 12.6 h, and median post-transplant hospital stay was 4 days (2–97) with 55 patients (15.8%) discharged home by the 2nd day, 141 (40.5%) by the 3rd day and 203 (58.3%) by the 4th day, which defined our Fast-Track group. The overall thirty-day-readmission rate was (34.5%), which became significantly lower (27.6% vs 44.1%, p=0.0014) in the Fast-Track group when compared to the regular discharge group. Patient survival was 87.6% at 1 year and 79.7% at 5 years. ConclusionFast-Tracking of Liver Transplant patients is very feasible and can be applied as the standard of care.