Red Cell Transfusion Requirements Research Articles

The impact of age, sex, comorbidities, and use of antithrombotics on the clinical course severity among patients surgically treated for urinary bladder tamponade.

To examine the relationship between clinical patient characteristics and the severity of the disease course in patients hospitalized due to urinary bladder tamponade. The severity was assessed based on hemoglobin (Hgb) levels upon admission, the requirement for red blood cell transfusion (RBCT), and length of hospital stay. A retrospective analysis was conducted at a single center, involving 75 patients who were hospitalized due to urinary bladder tamponade. Bladder cancer (33.3%) and postoperative bleeding (28%) were the most common causes of bladder tamponade. Patient age exhibited a negative correlation with Hgb levels upon admission (r = -0.539, P < 0.001) and a positive correlation with the quantity of administered RBCT units (r = 0.425, P < 0.001) and the length of hospitalization (r = 0.541, P < 0.001). The number of comorbidities exhibited a negative correlation with Hgb levels upon admission (r = -0.555, P < 0.001) and a positive correlation with the quantity of administered RBCT units (r = 0.522, P < 0.001) and the length of hospitalization (r = 0.543, P < 0.001). Patients taking antithrombotic therapy (AT) had lower mean Hgb levels on admission (87.8 ± 13.5 g/L vs. 107.6 ± 18.7 g/L, P < 0.001), a higher mean number of administered RBCT units (2.8 ± 2.1 vs. 1.1 ± 1.3, P < 0.001) and longer hospitalizations (4.6 ± 1.6 days vs. 3.1 ± 1.1 days, P < 0.001) compared to those not taking AT. Older patients with multiple comorbidities, particularly those taking AT, should be expected to have a more severe clinical course of bladder tamponade. Therefore, special clinical attention is necessary for this vulnerable patient group.

A retrospective comparison of abbreviated course “7+7” vs standard hypomethylating agent plus venetoclax doublets in older/unfit patients with newly diagnosed acute myeloid leukemia.

6507 Background: Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in older/chemotherapy ineligible patients with acute myeloid leukemia (AML). While the VEN label recommends continuous 28-day cycles, shortened VEN durations may mitigate cytopenias and improve tolerability. It is unknown how shorter VEN cycles compare to standard HMA+VEN in terms of efficacy/safety. Methods: We performed a retrospective comparison of patients with newly diagnosed (ND) AML treated with azacitidine (AZA) x 7 days plus VEN x 7 days (“7+7” regimen) at 7 French centers (n=82, Willekens, ASH 2022) vs patients treated with standard dose HMA+VEN (s-HMA/VEN) at a US center (n=173), generally consisting of 21-28 days of VEN. We compared composite complete remission rate (CRc, consisting of CR + CRi), overall survival (OS), event-free survival (EFS), and myelosuppression between regimens. Results: Baseline characteristics are shown in the table. The s-HMA-VEN group consisted of 10-day decitabine (DAC) in 59% with the remaining patients receiving 5-day DAC or 7-day AZA. The CRc rate was similar; 72% with “7+7” vs 71% with s-HMA/VEN (p=0.89). The CR rate was 57% with “7+7” vs 55% with s-HMA/VEN (p=0.72). Median cycles to first response was 1 in both groups, however 42% of responders on “7+7” required more than 1 cycle for first response whereas almost all responders on s-HMA-VEN (99%) had a first response after cycle 1. Median cycles to best response was 2 with “7+7” vs 1 with s-HMA-VEN (p=0.02). 4-week mortality was similar (2% with “7+7”, 6% with s-HMA-VEN; p=0.24). 8-week mortality was higher with s-HMA-VEN (17%) compared to “7+7” (6%) (p=0.02). The median OS was 11.2 months (2-year 28%) with “7+7” vs 10.1 months (2-year 33%) with s-HMA/VEN (p=0.93). Outcomes stratified by molecular groups will be updated at the meeting. Fewer patients required platelet transfusions during cycle 1 with “7+7” compared to s-HMA/VEN (62% vs 77%, p=0.01). The cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar. Conclusions: Acknowledging the limitations of a retrospective comparison across multiple centers, we did not observe a signal for a difference in efficacy between "7+7" vs standard VEN-based HMA doublets in ND-AML. The “7+7” regimen was associated with lower platelet transfusion requirements and lower 8-week mortality. [Table: see text]

The impact of infused red blood cell volume on major and bidirectional ABO-mismatched bone marrow transplantation

Background aimsABO incompatibility does not hinder bone marrow transplantation (BMT), but it has been associated with worse outcomes and additional adverse events. This study aimed to verify the impact of incompatible red blood cells (iRBCs) in allogeneic BMT and to determine a safe number of iRBCs to be infused. MethodsWe compared ABO-incompatible (iABO) allogeneic BMT (n = 42) with ABO-compatible allogeneic BMT (n = 44) and evaluated the impact of the number of infused iRBCs on outcomes and adverse events. ResultsThe iABO patients demonstrated delayed time to transfusion independence at 30 days and 60 days, increased requirement for red blood cell (RBC) transfusion and greater hemolysis signals and incidence of pure red cell aplasia. Neutrophil/platelet engraftment, length of hospitalization post-transplant, platelet units required, graft-versus-host disease occurrence and overall survival were similar in both groups. Patients in the iABO group received 1.03 × 1010 iRBCs/kg (range, 0.36–3.88). Infusion of iRBCs >1.0 × 1010 /kg was related to graft failure or death before neutrophil engraftment or platelet engraftment or both as well as increased plasma requirement and increased creatinine. Our results also suggest that antibody titers impact the transplantation scenario. ConclusionsThe iABO transplantation showed some unfavorable outcomes. It is important to monitor the value of iRBCs to be infused, considering the recipient antibody titers. We propose using the number of iRBCs (iRBCs/kg) as a dose parameter with regard to infused iRBCs. Further studies are necessary to clarify the maximum safe number of iRBCs in iABO transplants.

Hereditary hemorrhagic telangiectasia may be the most morbid inherited bleeding disorder in women

AbstractHereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder (BD) worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron-deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in the brain, lung, and liver, which can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), which is the most common inherited BD in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT vs VWD, recurrent epistaxis and gastrointestinal bleeding were more likely (odds ratio [OR], 32.73 [95% confidence interval, 13.81-71.80]; P < .0001 and 5.69 [2.59-12.89]; P < .0001) and heavy menstrual bleeding was less likely (OR, 0.32 [0.18-0.57]; P < .0001). Iron-deficiency anemia was significantly more likely, and the lowest hemoglobin was significantly lower in HHT than in VWD. The odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher—17-fold, threefold, and eightfold higher, respectively—and hospital admissions to manage disease complications were both ∼14 times more frequent in women with HHT vs those with VWD. In conclusion, much higher disease-related morbidity, mortality, and health care use were observed in women with HHT vs VWD, providing evidence that HHT may be the most clinically significant inherited BD in women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (β: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (β: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. Therapeutic/Care Management; Level III.

Intravenous iron administration before cardiac surgery reduces red blood cell transfusion in patients without anaemia

BackgroundReducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery. MethodsThis double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24–72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery. ResultsThe 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl−1 and 9.3 (1) g dl−1, respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl−1 and 11.8 (1.5) g dl−1, respectively (P=0.012). ConclusionsIn patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1–3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration. Clinical trial registrationNCT02939794.

Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.

High-dose melphalan (HDM) with autologous hematopoietic cell transplantation (AHCT) after induction chemotherapy is considered standard of care in transplant-eligible patients with newly-diagnosed multiple myeloma (MM). Alkeran melphalan has propylene glycol as a solvent (PG-mel) while Evomela utilizes a propylene glyclol-free formulation (PGF-mel). We evaluated the differences in efficacy and safety of the 2 formulations as there are no prospective head-to-head trials. We retrospectively reviewed the medical records of all 259 consecutive MM patients who received PGF-mel as part of HDM-AHCT at The Ohio State University (OSU). The comparator group was the preceding 255 patients who received PG-mel. Baseline patient characteristics were similar between the 2 groups. Post-AHCT rates of relapse were comparable in the PG-mel and PGF-mel groups. Some adverse events were observed at a higher frequency in the PG-mel group compared to the PGF-mel group (grade ≥ 2 mucositis, febrile neutropenia, other infectious complications, and acute renal insufficiency). Time to neutrophil engraftment was slightly longer in the PG-mel group while time to platelet engraftment was longer in PGF-mel group. Red cell transfusion requirement was higher with the use of PG-mel but not platelet transfusion. Duration of hospitalization was slightly shorter with PGF-mel but readmission rates within 30 days of discharge were higher. Considering possible confounding factors could possibly account for observed differences in some adverse events, the comparable treatment responses, and difference in cost of the 2 formulation, The OSU reverted to PG-mel as the preferred formulation for HDM-AHCT in MM.

The pressure field as a methodology for fluid management and red cell preservation during cardiac surgery

PurposeAnemia and red cell transfusion contribute to morbidity and mortality of surgery. The concept of patient blood management to mitigate preoperative anemia, optimize coagulation, conserve red cells intraoperatively and accept lower post-operative transfusion thresholds has recently gained widespread acceptance across a range of surgical disciplines. Fluid administration is likely to contribute significantly to perioperative anemia and red-cell transfusion requirements, yet a robust basis for managing fluid administration in this context has not been articulated. There is an urgent need for this.MethodsWe developed ‘the pressure field method’ as a novel approach to guiding the administration of fluid and drugs to optimize tissue perfusion. The pressure field method was used for the intraoperative management of 67 patients undergoing semi-elective cardiac surgery. We compared intraoperative anemia and transfusion requirements in this cohort with a conventional group of 413 patients undergoing cardiac surgery.ResultsIn the pressure field group, no patients required transfusion whereas in the conventional group, 16% required transfusion during bypass and these patients received an average of 2.4 units of packed red cells (P < 0.0001). The average decrease in hemoglobin in the pressure field group was only 13 g/L, whereas in the conventional group it was 52 g/L (P < 0.0001). 80% of the pressure field group received no intravenous fluid during cardiac surgery, and the average intraoperative fluid load was 115 mL.ConclusionThe pressure field method appears to reduce transfusion requirements due to decreased intraoperative fluid loading.

Replacing Procarbazine with Dacarbazine in Escalated Beacopp Dramatically Reduces the Post Treatment Haematopoietic Stem and Progenitor Cell Mutational Burden in Hodgkin Lymphoma Patients with No Apparent Loss of Clinical Efficacy

Introduction When treating Hodgkin lymphoma (HL), it is common UK practice to modify escalated BEACOPP (eBPP) by removing oral procarbazine and replacing it with intravenous dacarbazine (250mg/m2 D2-3) to reduce haematopoietic stem cell and gonadal toxicity. A similar replacement of procarbazine in COPP (to COPDac) has reduced gonadal toxicity and conferred a comparable long-term event-free survival to children (EuroNet-PHL-C1 trial; Mauz-Körholz et al Lancet Oncol 2021). Our own retrospective study has shown that adults treated with first-line escalated BEACOPDac (eBPDac) have a reduced blood transfusion requirement and earlier return of menstrual periods compared with real-world eBPP patients (pts) with no loss of clinical efficacy compared to HD18 eBPP pts (Santarsieri et al Blood 2021). To better understand the toxicity differences, we performed this study to compare the haematopoietic stem and progenitor cell (HSPC) mutational burden in pts who have received procarbazine and dacarbazine containing regimens. Chemotherapeutic agents are known to damage DNA and this mutational process likely causes many of the long-term chemotherapy toxicities. Little is known about the mutational signatures and mutation burdens caused by HL therapies, although a novel mutational signature (SBS25) has recently been described in two HL cell lines (Petljak et al Cell 2019). Methods We whole genome sequenced 6-8 single-cell derived HSPC colonies from each of 12 advanced stage HL pts (n = 91; mean sequencing depth 26X). The pts were all in remission > 6 months and had been previously treated with either eBPDac (6 cycles (n=2); 4 cycles (n=2)), eBPP (6 cycles (n=3); 5 cycles (n=1); 4 cycles (n=1)) or ABVD (n=3; all 6 cycles). Single HSPC somatic mutation burdens and mutation spectra from these chemotherapy exposed individuals were compared to those from our previously published normal cohort (n = 110; mean sequencing depth 24X) (Mitchell et al Nature 2022). In addition we have updated the outcomes of our retrospective multi-centre study of pts treated with eBPDac including additional pts and longer follow-up of the entire cohort. Mutational analysis The somatic single nucleotide variant mutation burden in normal adult HSPCs ranges from approximately 400 aged 20yr to 1500 aged 80yr; an average of 18 mutations accumulate with every year (Figure 1A). The HSPCs from ABVD and eBPDac-treated pts had similar minor excess somatic mutation burdens compared to aged-matched normal HSPCs of 183 (CI95%= 110-256) and 291 (CI95%= 242-340) mutations respectively. In contrast, the HSPCs from eBPP-treated pts had a striking and significantly increased excess mutation burden of 1153 (CI95%= 937-1369). Of the eBPP pts, the single patient who received 4 cycles had the lowest number of excess mutations, but noting the inter-patient variation, we cannot yet conclude that eBPP cycle number correlates with the number of mutations. Descriptive analysis of the mutational profiles (Figure 1B) revealed that every patient who received procarbazine had a clear SBS25-like mutational signature, characterised by T>A base substitutions, demonstrating for the first time that this DNA mutational signature is directly attributable to procarbazine. Clinical data analysis The clinical data presented last year have been updated with more pts and longer follow-up (n=288; median 2.3 yr). With this high-risk group of advanced stage pts, our data suggest that the eBPDac pts have reduced red cell transfusion requirements, reduced hospitalisation, improved menstrual period recovery and improved sperm count preservation compared with eBPP pts. The eBPDac 24-month PFS is similar to HD18 3-yr PFS (94.9% vs 92.3%) and appears superior to RATHL 5-yr PFS (81.4%). The eBPDac 24-month OS estimate is 99%. Conclusions We have shown that dacarbazine-containing regimens (ABVD and eBPDac) confer a lower mutation burden to HSPCs compared with procarbazine-containing eBPP and that procarbazine is the agent responsible for the SBS25 mutational signature. This work provides a model example of how genomic analysis could be used to inform therapeutic decision making in cancer. Our retrospective analysis provides strong supportive evidence that eBPDac is a highly efficacious HL treatment and noting the clear benefits in terms of HSPC genomic health, we would encourage clinicians offering eBPP to HL pts to consider replacing procarbazine with dacarbazine. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Role of Thromboelastogram in monitoring the activation of the coagulation pathway and assessing the associated risk factors for hypercoagulable state in transfusion dependent thalassemia patients

BackgroundThromboembolic events are rare but one of the fatal complications in thalassemia. Assessment of the hypercoagulable state is not done regularly, and we have assessed the utility of Thromboelastography (TEG) for monitoring the activation of the coagulation pathway in patients with thalassemia. MethodologyA prospective single-center cohort study was conducted in a tertiary care set-up. Transfusion Dependent Thalassemia patients registered with the pediatric unit were screened for hypercoagulability using TEG during six months of the study period and followed up for three years for the development of thromboembolic events. Patient demographics, history of splenectomy, Serum ferritin levels and annual red cell transfusion requirement (mL/kg/year) were assessed. TEG parameters used were R time, K time, alpha angle, Maximum amplitude, Clot index, and Lysis 30. The thrombin generation test (V Curve) obtained from the first-degree derivate of the TEG velocity curve was also used for analysis. ResultsA total of 34 patients were recruited during the six months study period with an average age of 10.6 years ( ± 5.47). The average pre-transfusion hemoglobin level and the volume of packed red cells received were 7.24 g/dL and 152.82 mL/kg/year respectively. The TEG tracing was suggestive of a hypercoagulable state in 58.82% of patients. The mean values of angle (70.74), MA (64.16), CI (2.65) and TG (774.43) in TDT patients compared to age matched reference range (62.81, 57.99, 0.8, 577.83 respectively) was suggestive of prothrombotic changes. Annual blood transfusion requirement was negatively correlated with hypercoagulable status (‐0.344, CI= -0.68 to 0.08). One out of 34 patients developed corona radiata infarct (with annual blood requirement; 112.7 mL/kg/Year). The risk to develop a hypercoagulable state appeared to be higher when the volume of RBCs transfused was less than 154 mL/kg/Year. ConclusionTDT patients are at risk of developing thromboembolism, and screening with TEG may be useful to identify those at high risk.

Prehospital low titer group O whole blood is feasible and safe: Results of a prospective randomized pilot trial.

Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remain limited. We performed a single-center, prospective, cluster randomized, prehospital through in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (systolic blood pressure ≤90 mm Hg and heart rate ≥108 beats per minute or systolic blood pressure ≤70 mm Hg for patients at risk of hemorrhage). Primary outcome was feasibility. Secondary outcomes included 28-day and 24-hour mortality, multiple organ failure, nosocomial infection, 24-hour transfusion requirements, and arrival coagulation parameters. Between November 2018 and October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent-to-treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented. Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized. Therapeutic/Care Management, Level II.

Predictors of Mortality and Outcomes of Liver Transplant in Spur Cell Hemolytic Anemia

BACKGROUND :Spur cell hemolytic anemia (SCHA) is a rare, acquired, non-immune hemolytic anemia of decompensated cirrhosis resulting from abnormal lipid composition of the red cell membrane. Treatment is limited to red cell transfusion. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited; published data on SCHA are limited to single-patient case reports and small single-center case series. The independent prognostic impact of SCHA on patients with cirrhosis remains unclear, and it is not known if hemolytic anemia severity has a significant impact on survival of these patients. As a result, SCHA is not formally considered during liver transplant evaluation, and patients do not receive MELD exception points for this diagnosis.METHODS :We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Strict diagnostic criteria for SCHA were applied, requiring all of the following: (1) decompensated cirrhosis; (2) anemia; (3) objective laboratory evidence of hemolysis; (4) no alternate contributing cause of hemolysis or acanthocytosis; and (5) chart documentation of a confirmed diagnosis of SCHA incorporating peripheral blood film examination. The primary outcome was mortality at 3 months after date of SCHA diagnosis. The impact of hemolytic parameters on 3-month mortality was evaluated utilizing multivariable logistic models. Observed mortality vs. expected mortality (per MELD-Na score and Child-Turcotte-Pugh class) was compared using standardized mortality ratios. Given the limited survival of this population, red cell transfusion dependence was defined as 4 or more units of red cells transfused during the 60-day peri-diagnostic period.RESULTS :Patients: 69 patients with SCHA were included (FIGURE 1). The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Alcohol contributed to the etiology of cirrhosis in 53 patients (76.8%). The median (IQR) survival from SCHA diagnosis of patients not receiving liver transplant was 58 (23-113) days. 39 patients (56.5%) were red cell transfusion-dependent. Hematologic parameters are described in TABLE 1.Outcomes of Liver Transplant: All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with an improvement in median hematocrit from 22.1% to 34.6% post-transplant (P=0.001) (TABLE 2) and excellent post-transplant outcomes, with 9 patients still alive after 6.1 years median follow-up.Independent Predictors of Mortality in SCHA: In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an OR for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality (FIGURE 2).Performance of MELD-Na and Child-Turcotte-Pugh Scores in Estimating 90-Day Mortality: MELD-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)], FIGURE 3.CONCLUSIONS :In this largest study of SCHA to date, SCHA was associated with substantial excess mortality than was predicted by MELD-Na or Child-Turcotte-Pugh scores. Several clinical and laboratory parameters of hemolytic anemia severity, including transfusion burden, hemoglobin, and markers of hemolysis were each independent predictors of 90-day mortality in SCHA. Despite its unique morbidity as a complication of decompensated cirrhosis, outcomes of liver transplant were excellent in all 11 patients undergoing this intervention, with total resolution of SCHA and no evidence of recurrence. These findings should promote greater awareness of SCHA as a clinical entity and broader consideration of MELD exception points for afflicted patients when transplant-eligible. [Display omitted] DisclosuresAl-Samkari: Novartis: Consultancy; Amgen: Research Funding; Argenx: Consultancy; Rigel: Consultancy; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy.

Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia.

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Sixty-nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty-nine patients (56.5%) were red blood celltransfusion-dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post-transplant (p= .001) and excellent post-transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an odds ratio (OR) for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality. Model for end-stage liver disease (MELD)-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD-Na or Child-Turcotte-Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90-day mortality.

Red Blood Cell Transfusion and its Relationship with Pedicle Thrombosis in Microvascular Free Flaps.

Free flaps have become a highly valuable tool for complex reconstructive surgeries. The requirement of red blood cell transfusion (RBCT) during the perioperative period is common and its effect on the free flap survival is debatable. The aim of this study was to determine the relationship between perioperative RBCT and vascular pedicle thrombosis (VPT). For this study 302 free flaps performed between January 2006 and December 2019 were retrospectively analyzed. It included their characteristics from before, during, and after the surgical procedure. The incidence of VPT and flap survival were calculated based on Kaplan Meier's method and the relationship between VPT and perioperative variables were analyzed by Cox regression models. The transfusion group was represented by 62 flaps (20.5%) and no transfusion by 240 flaps. The overall transfusion requirement was 20.5% and the cumulative incidence of VPT was 9.11%. A statistically significant relationship was not demonstrated between flap survival and transfusion status (HR = 1.73 IC 95%: 0.5 to 3.96; p = 0.192) (p = 0.192) independently from the number of units transfused, the preoperative diagnosis of anemia, and the type of flap used and did not establish an increased risk of VPT. This study did not demonstrate an association between RBCT during preoperative period and the risk for VPT or microvascular free flap survival rate on postoperative follow up.

Clinical outcomes of esophagogastroduodenoscopy in critically ill patients using high-dose proton pump inhibitor for suspected bleeding: A retrospective cohort study.

Esophagogastroduodenoscopy (EGD) is a useful procedure performed for gastrointestinal (GI) bleeding. No definite clinical guidelines recommend EGD implementation in intensive care unit (ICU) patients with suspected GI bleeding. The objective of this study was to compare the clinical effectiveness of EGD in critically ill patients who are using high-dose proton pump inhibitor (PPI) for suspected GI bleeding.We retrospectively analyzed ICU patients using high-dose PPI for suspected GI bleeding from January 2012 to September 2020. Major cases of GI bleeding, such as those with hematemesis and hematochezia, were excluded, and 1:1 propensity score matching was performed. The change in hemoglobin level, requirement of red blood cell transfusion, re-suspected bleeding event, length of ICU stay, and ICU mortality were compared between the EGD and non-EGD groups.Of the 174 subjects included, 52 patients underwent EGD within 24 hours of PPI administration. In the EGD group, 22 (42.3%) patients showed normal findings, while esophagitis and gastritis were most common abnormal finding (n = 11, 21.2%), and 14 patients (26.9%) underwent a hemostatic procedure. While comparing the 2 groups, the EGD group required a higher amount of red blood cell transfusion (packs) than the non-EGD group for a week (3.04 ± 0.44 vs 2.07 ± 0.25, P = .01). There was no significant difference in the change in hemoglobin level after 1 week (P = .15). After propensity score matching, the EGD group showed similar the requirement of red blood cell transfusion and change in hemoglobin level for a week (P = .52, P = .97, respectively). In analyses for all patients and propensity score matched patients, there was no statistically significant difference in term of re-suspected bleeding event rate, duration of ICU stay, and ICU mortality. However, re-suspected bleeding event rate and ICU mortality were lower trend in the EGD group than the non-EGD group.This study showed that EGD had no definite clinical benefit in ICU patients using high-dose PPI for suspected GI bleeding and aggressive EGD is not necessarily recommended. However, it is necessary to consider EGD in patients who are tolerant.

Withdrawal: “Effect of single preoperative ferric carboxymaltose injection on perioperative transfusion in patients undergoing total hip arthroplasty: A retrospective analysis” Hyun‐Jung Shin, Hun‐Taek Lee, Hyo‐Seok Na

Despite ongoing efforts to reduce perioperative transfusion, there is still high chance of transfusion in total hip arthroplasty (THA). We investigated the requirement of red blood cell (RBC) transfusion according to the administration of single preoperative ferric carboxymaltose (FCM) in patients undergoing THA. This retrospective study included the patients undergoing unilateral THA from November 2014 to July 2018, who received FCM (FCM group) at 2 weeks prior to the surgery or who did not (Non-FCM group). A propensity-score matching method was used to balance the two groups for analysis. The primary endpoint was to evaluate if there was any difference in requirement of RBC transfusion between the two groups. This study included 1,032 cases of THA for final analysis, and the cases were divided into the FCM group (n = 568) and Non-FCM group (n = 464). Propensity matching produced 389 patients in each group. In the FCM group, the amount (0.4 vs. 0.6 units) and incidence (21% vs. 31%) of RBC transfusion was significantly lower compared with the Non-FCM group (P = 0.035 and P = 0.003, respectively). Single preoperative FCM administration without any other supplementation could reduce the requirement of RBC transfusion in patients undergoing THA. This study suggests that single preoperative FCM administration can be recommended as a simple and easy patient blood management strategy in addition to other methods for reducing the RBC transfusion in THA.

Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome

IntroductionComplement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) is effectively prevented by the terminal-complement inhibitor eculizumab, reducing symptoms and protecting against the clinical consequences of the disease, such as thrombosis and renal failure. Due to the continued activation of the proximal complement cascade upstream of C5, PNH red cells become opsonized with fragments of C3, leading to extravascular hemolysis and a continued transfusion requirement in a proportion of patients. Lactate dehydrogenase (LDH) is utilised as the main indicator of hemolysis in PNH but is particularly a measure of intravascular rather than extravascular hemolysis and therefore is not necessarily elevated in proportion to transfusion requirement due to C3-loading. We therefore conducted data analysis to determine whether other parameters were more indicative of extravascular hemolysis.MethodsData from patients with PNH treated in the Leeds centre of the UK PNH National Service was reviewed retrospectively. Criteria for inclusion in the analysis were treatment with eculizumab for ≥13 months, a mean platelet count >50 x 109/L and mean absolute neutrophil count >0.5 x 109/L (to exclude patients with significant bone marrow failure). Mean values for hemoglobin, absolute reticulocyte count, LDH (adjusted for upper limit of normal), total bilirubin and the proportion of PNH red cells loaded with C3 were collated covering a 48-month period. C3 loading of red cells was assessed by flow cytometry (Sutherland et al., Curr Protoc Cytom. 2015). Red cell transfusion requirements for the latest 12 months and latest eculizumab dosage were also collected.ResultsOne hundred and forty-one patients were identified for inclusion by the above criteria; 70 males and 71 females. The median hemoglobin level for all patients was 109g/l. Seventy-two percent had a mean hemoglobin below 120g/l despite treatment with eculizumab and all patients had variable amounts of C3 on their red cells demonstrating that some degree of extravascular hemolysis is always seen. During the latest 12 months, 51 (36%) patients received at least one transfusion, with 23 (16%) requiring 3 or more transfusions. Thirty (21%) patients were receiving a higher dose of eculizumab (1200mg or more every 2 weeks) due to either sub-therapeutic eculizumab levels and/or measureable terminal complement levels, assessed by the CH50, at the standard dose of 900mg every two weeks.Patients were stratified by both reticulocyte count and LDH and the means for each parameter calculated as shown in Table 1. Bilirubin, C3 loading, transfusion requirement and requirement for an increased dose of eculizumab all correlated better when stratifying by reticulocytes rather than by LDH.When patients were scored on the severity of C3 loading, bilirubin values and reticulocyte count, those with the worst (highest) joint scores were 3 times more likely to be transfused. 72/141 (51%) patients had all three of the following: reticulocyte count <230 x 109/l, bilirubin <30umol/l and less than 30% of their PNH red cells staining for C3. 55 of these 72 (76%) were not transfused in the last 12 months. In contrast 9 patients had reticulocytes >230, bilirubin ≥30 and C3-loading ≥30% and 7 of these 9 continued to require transfusions.ConclusionReticulocyte count appears to be a better indicator of extravascular hemolysis than LDH, correlating more strongly with raised bilirubin, increased C3 loading of PNH red cells and increased transfusion requirement. Using these parameters patients who are more likely to continue to require transfusion support on eculizumab can be identified. Such an approach may be used to identify patients who are more likely to benefit from inhibition of the complement cascade that could reduce the level of C3-associated extravascular hemolysis. [Display omitted] DisclosuresRichards:Alexion Pharmaceuticals, Inc.: Honoraria. Munir:Alexion Pharmaceuticals, Inc.: Honoraria; Gilled: Honoraria; AbbVie: Honoraria; Janssen: Honoraria; Roche: Honoraria. Griffin:Alexion Pharmaceuticals, Inc.: Honoraria. Arnold:Alexion Pharmaceuticals, Inc.: Honoraria. Hill:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hillmen:Roche: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding.

Red Cell Alloimmunisation Is Associated with Development of Autoantibodies and Increased Red Cell Transfusion Requirements in Myelodysplastic Syndromes (MDS)

Introduction: Up to 90% of MDS patients require red blood cell (RBC) transfusions and 30-45% become RBC transfusion dependent (RBC-TD). However, literature addressing RBC alloimmunisation in MDS is limited. This study evaluates the incidence and clinical impact of RBC alloimmunisation in 817 adult MDS (or related disorders) patients enrolled in the South Australian-MDS registry.Methods: Demographic, clinical, laboratory and treatment (including transfusions) details of patients with at least 6-month follow up were analysed. RBC-TD was defined as >1unit of RBC transfusion every 8 weeks over a period of 4 months. Azacitidine, intensive chemotherapy or allogeneic stem cell transplantation were denoted as disease modifying therapies (DMT).Results: Median age at diagnosis was 73 years and 66% were male. During the study, 695 (85%) patients received >1 RBC unit, and 98 developed 175 alloantibodies. Of these, 11 patients developed alloantibodies following MDS-unrelated RBC transfusion well before the MDS diagnosis, and seven developed antibodies before their first documented RBC transfusion. Remaining 80 patients developed alloantibodies following MDS-related RBC transfusion. The cumulative incidence of RBC alloimmunisation with death as competing risk was 11% at 50 months following the first MDS-related RBC transfusion (Fig. 1A). Importantly, 73% and 50% of allo-immunised patients developed alloantibodies during first 20 RBC transfusions and within 6 months of commencement of RBC transfusion, respectively. Of the 98 allo-immunised patients, 50 (51%) developed one alloantibody, while 48 (49%) developed multiple alloantibodies. Rh (93/175; 54%) and Kell (41; 24%) alloantibodies were most frequent followed by Kidd (13, 7.5%) and Lutheran (10, 5.7%). Within Rh system anti-E, anti-C and anti-D were the most frequent.Autoantibodies were detected in significantly more alloimmunised than in non-alloimmunised patients (65% vs. 18%, p<0.0001; Fig 1B) and >85% autoantibodies occurred within 5 months of alloimmunisation. Though 73% of alloimmunised patients developed alloantibody during their first 20 RBC units, total RBC units transfused were significantly higher in alloimmunised compared to non-alloimmunised patients (90±100 vs. 30±52; p<0.0001) (Fig. 1C). In alloimmunised patients, total RBC transfused after alloimmunisation were significantly higher than before alloimmunisation (p<0.0001, Fig. 1D). In MDS patients, multiple other factors such as disease progression, infection, bleeding and treatment can influence RBC-transfusion intensity. Hence, we evaluated RBC-transfusion intensity in 33 patients meeting strict inclusion criteria (Fig. 2A). In these patients, RBC-transfusion intensity substantially increased after alloimmunisation (p=0.002; Fig. 2B-C).We then evaluated risk factors for alloimmunisation using RSF and R-PART analysis. RBC units transfused before alloantibody formation was the most important predictor of alloimmunisation, followed by RBC-TD status, treatment type and age. A classification tree using RPART suggested that 46% patients who were RBC-TD developed an alloantibody within first 20 units of RBC transfused. Landmark analyses using CRR model both at baseline (using age, sex, WHO subtype, IPSS-R risk groups and type of treatment) and at six months (baseline factors plus number of RBCs transfused within 6 months and RBC-TD status at 6 months) following the start of RBC transfusions were performed. At both time-points, alloimmunisation risk was significantly lower in DMT treated patients (HR -3.04; p=0.0023) and appears unrelated to number of RBC transfusions as patients managed with DMT received significantly more RBC units than patients treated with supportive care (p<0.0001).Conclusion: This study characterises alloimmunisation in a large statewide cohort of MDS patients and demonstrates a significant increase in RBC transfusion requirements following alloimmunisation, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical haemolysis. Use of DMT is associated with lower alloimmunisation risk. Strategies mitigating alloimmunisation risk are critical for optimising RBC-transfusion management. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio. We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78-1.14] vs. 0.75 [IQR 0.57-0.99]; p < 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75-245] vs. 135 [IQR 94-222] mL; p = 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%] p = 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160-210] vs. 280 [IQR 250-300] mg; p < 0.001). Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C). Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients. ClinicalTrials.gov Unique identifier NCT03532594.

Western Australian Peritonectomy Service: a review of the first 6 years of operation of a low-volume peritonectomy centre.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal early chemotherapy has gained acceptance as the standard of care for peritoneal surface malignancy over the past decade. This study reports the results of the first 6 years of activity of the Western Australian Peritonectomy Service to compare outcomes of a low-volume centre with world standards. An audit of all patients who received CRS ± hyperthermic intraperitoneal early chemotherapy treatment at the Western Australian Peritonectomy Service in its first 6 years of operation was performed and results were compared to the recent world literature. A total of 130 patients were treated with 150 CRS procedures, including 50 pseudomyxoma peritonei (PMP), 53 colorectal cancers (CRCs), 27 appendix adenocarcinomas (AAs) and 20 other cancers. The median operating time was 12 h with median length of hospital stay of 15 days. Perioperative mortality was 0.67% and Clavien-Dindo III/IV morbidity was 20%. The mean packed red cell transfusion requirement was 0.34 units/case. Post-discharge readmission rate was 25% and the return to theatre rate was 13%. The 4-year overall survival rates for PMP, CRC and AA were 97%, 49% and 81%, respectively. The 3-year disease-free survival rates for PMP, CRC and AA were 74%, 26% and 36%, respectively. A CRS centre averaging 25 cases per year can achieve strong outcomes in line with high-volume world centres.