Increased Transfusion Requirements Research Articles

Perioperative antithrombotic medication: An approach for the primary care clinician.

The primary care clinician faces many challenges and is often left to manage complex pathology because of resource constraints at higher levels of care. One of these complex conditions is the perioperative management of antithrombotic medication. This narrative review is focused on helping the clinician navigate the complex path and multiple guidelines related to the perioperative use of antithrombotic medication. Perioperative antithrombotic guidelines (American College of Chest Physicians, European Society of Regional Anaesthesia, and American Society of Regional Anesthesia) and relevant publications were identified by a PubMed search using the terms perioperative AND anticoagulants OR antithrombotics AND guideline. Issues relevant to clinical practice were identified, and attempts were made to explain any ambiguity that arose. Adhering to basic pharmacological principles and evidence-based guidelines allows for the safe usage of antithrombotics. Knowing when to stop, continue, bridge and restart antithrombotic medication prevents perioperative morbidity and mortality. Stopping antithrombotic medication too early can lead to thromboembolic complications associated with their primary disease process. Not stopping antithrombotic medication or stopping it too late can potentially cause life-threatening bleeding, haematomas and increased transfusion requirements.

A prospective study of all-trans retinoic acid plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia.

6545 Background: Over the decade, anthracycline and cytarabine-based intensive chemotherapy remains the standard of care for acute myeloid leukemia (AML) but is hampered by serious toxicities like myelosuppression, increased transfusion requirement and disappointing clinical outcomes among the so-called poor-prognosis AML subsets. BCL-2 inhibitor plus azacitidine (AZA) has become a preferred treatment for AML, but the remission rate and overall survival (OS) are suboptimal. Apart from hematologic toxicities, 70.0% of patients were RBC transfusion dependent and 58.6% were platelet transfusion dependent. At present, all-trans retinoic acid (ATRA) is used as a differentiation drug, and there is no combination regimen with BCL-2 inhibitor. This study aimed to assess the efficacy and safety of ATRA plus venetoclax and AZA for newly diagnosed AML. Methods: This study enrolled 35 patients (≥18 years) with newly diagnosed AML between 2022 and 2023. For induction, patients received AZA (75 mg/m²) from Day 1 to 7, venetoclax at a target dose of 400 mg/d from Day 2 to 10, and ATRA (45 mg/m²/d) from Day 12 to 28 of each 28-day cycle for up to 2 cycles or until disease progression. Patients who achieved complete remission (CR) after two cycles of induction therapy received bone marrow transplantation or consolidation at their own discretion. For consolidation, patients received ATRA (45 mg/m²/d) from Day 1 to 21 and AZA (75 mg/m²) from Day 1 to 7 of each 28-day cycle for up to 4 cycles or until disease progression. For maintenance, patients received ATRA (45 mg/m²/d) for 21 days per cycle plus AZA (75 mg/m²). Maintenance therapy was given every 3 months until disease progression and ATRA was provided during intermissions. The primary endpoint was the composite CR rate (CR and CR with incomplete hematologic recovery) at the end of cycle 1 of inductive therapy. Results: As of now, the composite CR rate reached 74% (26/35) and the objective response rate reached 91% (32/35). The composite CR was 73% (11/15) in the adverse risk group and 75% (15/20) in the favorable-intermediate risk group at the end of cycle 1. Thirty-three patients entered cycle 2. The cumulative composite CR rate reached 91%(30/33) after 2 cycles of induction therapy. The median event-free survival was 390 days, and the median OS was 573 days. Platelet transfusion independence occurred in 17% (6/35) patients in cycle 1 and 73% (24/33) in cycle 2. Furthermore, 20% (7/35) and 73% (24/33) patients were RBC transfusion independent in cycle 1 and 2, respectively. Any-grade infections occurred in 74% (26/35) patients, including 12 before admission. Conclusions: The treatment regimen achieved a high composite CR rate and was well tolerated, with reduced hematologic toxicities in cycle 2 of induction therapy. Both adverse risk and favorable-intermediate risk patients benefited from the regimen, which holds promise for treating AML in adult patients. Clinical trial information: NCT05654194 .

Postoperative bleeding after complex abdominal wall reconstruction: A post hoc analysis of a randomized clinical trial

BackgroundAbdominal wall reconstruction requires extensive dissection of the abdominal wall, exposure of the retroperitoneum, and aggressive chemoprophylaxis to reduce the risk of thromboembolic complications. The need for early anticoagulation puts patients at risk for bleeding. We aimed to quantify postoperative blood loss, incidence of transfusion and reoperation, and associated risk factors in patients undergoing complex abdominal wall reconstruction. MethodsAll patients underwent a posterior component separation with transversus abdominis release and placement of retromuscular mesh for ventral hernias <20 cm wide and were enrolled in a clinical trial assessing the utility of trans-fascial mesh fixation. A post hoc analysis was performed to quantify postoperative hemoglobin drop, blood transfusions, and procedural interventions for ongoing bleeding during the first 30 postoperative days. Multivariate logistic regression was used to identify predictors of transfusion. ResultsIn 325 patients, hemoglobin decreased by 3.61 (±1.58) g/dL postoperatively. Transfusion incidence was 9.5% (n = 31), and 3.1% (n = 10) required a surgical intervention for bleeding. Initiation of therapeutic anticoagulation postoperatively resulted in a higher likelihood of requiring surgical intervention for bleeding (odds ratio 10.4 [95% confidence interval 2.75–43.8], P < .01). Use of perioperative therapeutic anticoagulation was associated with higher rates of transfusion (odds ratio 3.51 [95% confidence interval 1.34–8.53], P < .01). Neither intraoperative blood loss nor operative times were associated with an increased transfusion requirement or need for operative intervention. ConclusionPatients undergoing transversus abdominis release are at a high risk of postoperative bleeding that can require transfusion and reoperation. Patients requiring postoperative therapeutic anticoagulation are at particularly high risk.

Intraoperative renal replacement therapy during liver transplantation in children: Safety, efficacy and impact on survival.

Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not. Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar. ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population.

Angioembolization for splenic injuries: does it help? Retrospective evaluation of grade III–V splenic injuries at two level I trauma centers

BackgroundSplenic angioembolization (SAE) has increased in utilization for blunt splenic injuries. We hypothesized lower SAE usage would not correlate with higher rates of additional intervention or mortality when choosing initial...

Paroxysmal Nocturnal Haemoglobinuria (PNH) Arising from Non-Canonical Mutations

Introduction Acquired somatic mutations in the X-linked PIGA gene are the most commonly described pathological mutations found in the serious haematopoietic disorder paroxysmal nocturnal haemoglobinuria (PNH), though incidental cases of mutations in PIGT, PIGB and PIGV have been reported. Mutations in the family of 20 PIG (phosphatidylinositol glycan) genes can disrupt biosynthesis of glycosylphosphatidylinositol (GPI) anchors, critical for tethering many important proteins, including the vital complement regulators CD55 and CD59, to the cell membrane. Their absence in PNH leads to complement dysregulation and complications including potentially life-threatening haemolysis and thrombosis, which may be mitigated by lifelong anti-complement therapy. From the cohort of 273 PNH patients currently on complement inhibitor therapy at the Leeds National PNH Centre we have identified 37 patients whose diagnostic flow cytometry report or clinical course differs significantly from expectation, particularly with evidence of inflammatory presentations, which may be indicative of an alternative, non- PIGA, aetiology. Methods Patients consented to the Leeds PNH Research Tissue Bank with unusual clinical and laboratory presentations were identified, genomic DNA was extracted from peripheral blood and initially screened by targeted high sensitivity NGS of the PIGA gene. From the first ten patient samples sequenced, three lacked any evidence of PIGA mutations and so whole exome sequencing (WES) was carried out. Results Patient 1:An 80 year old man, diagnosed with MDS with rearrangement of chromosomes 3 and 7 resulting in a dicentric chromosome and loss of chromosome 20q, was diagnosed with PNH following an increase in transfusion requirement. In addition to classical symptoms of PNH he was diagnosed with seronegative rheumatoid arthritis. Flow cytometry showed an unusual PNH phenotype with a large population of partially GPI-anchor deficient cells only (Table 1). Symptoms improved on eculizumab but he remained transfusion dependent and the disease later transformed to acute myeloid leukaemia. WES: exonic frameshift insertion in PIGT (figure1), pathogenic variant rs760395465. Patient 2:A 34 year old woman presented with a 13 year history of intermittent episodes of generalized urticaria associated with nausea, vomiting, general malaise and myalgia, increasing in intensity and latterly being associated with haemoglobinuria, lethargy and jaundice leading to a PNH diagnosis. Episodes were triggered by pregnancy or infections, but she remained asymptomatic between attacks. Flow cytometry revealed a PNH clone with a majority of cells being partially GPI deficient. She responds well to C5 inhibition with no further symptoms, including urticaria. WES: exonic frameshift insertion in PIGT (figure 1), pathogenic variant rs760395465. Patient 3: A 14 year old girl presented with intermittent episodes of urticaria and severe lethargy and was diagnosed with symptomatic significant transfusion-dependent PNH, with completely GPI-deficient cells. Diagnosis followed an episode of massive haemolysis resulting in transient acute renal failure requiring haemodialysis. She commenced anticoagulation initially until eculizumab was approved 2 years later; despite occasional episodes of breakthrough haemolysis she displays no further urticaria. She has also had symptoms of diffuse arthralgia. WES: stopgain mutation in PIGV (figure1), pathogenic variant rs145160045. Conclusions These cases add to the emerging picture of non- PIGA associated PNH cases and suggest that the presence of joint problems and episodic urticaria may be sufficient indication to prompt screening for alternative causative mutations. Similar to the previously reported PIGB mutated case, the patients with PIGT mutations only had partially deficient cells. It is important to fully characterise these emerging non-canonical variants in order to improve our understanding of the pathophysiology of this disorder and to provide more individualised care.

Considering Older Patients As Candidates for Auto Stem Cell Transplants: A Comprehensive Study on Toxicities and Survival Analysis

Introduction: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are commonly used for relapsed/refractory (R/R) Hodgkin (HL) and non-Hodgkin lymphoma (NHL). However, concerns about treatment-related mortality (TRM) and toxicity limit its use in older patients (pts). Existing evidence suggests higher rates of complications and inferior overall survival (OS) in older pts, but conflicting findings suggest that outcomes may be influenced by comorbidities rather than age ( Lahoud O, Curr Oncol Rep. 2015). Our study comparing ASCT outcomes and toxicities in lymphoma pts in younger and older age groups. Methods: In this retrospective study, we analyzed lymphoma pts who underwent ASCT at the Princess Margaret Cancer Centre from January 2015 to December 2019. After Institutional Review Board approval, clinical data was collected from institutional databases and patient charts. The hematopoietic cell transplantation comorbidity index (HCT-CI) and Charlson Comorbidity Index (CCI) were retrospectively calculated. Response assessment was done by Lugano 2014 classification. Grade 3-5 nonhematologic toxicities were collected from admission to day 100 using Common Terminology Criteria for Adverse Events version 5. Overall survival (OS) and progression-free survival (PFS) were calculated from date of transplant to death or disease progression. OS and PFS assessed via Kaplan-Meier; log rank tests and Cox regression performed. The patients were divided into two age groups: Group A (&amp;lt;65 years) and Group B (≥65 years). Results: There were 334 pts who underwent ASCT. 332 pts were analyzed; 2 pts were lost to follow-up and 16 pts were day 1 transfers, making acute toxicity data unavailable. The median age was 53 (range: 18-71), 17% of pts being aged ≥65. The majority of pts (69%) had NHL (table 1). The Eastern Cooperative Oncology Group (ECOG) performance status was ≤1 for 91%. Group B had a higher proportion of pts with ECOG score =2 (18% vs 7%, p &amp;lt; 0.001 ) and higher CCI (88% vs 27% , p &amp;lt; 0.001). NHL and mantle cell lymphoma (MCL) were more prevalent in Group B (93%, 23% vs 68%, 12% respectively, p&amp;lt; 0.001). Thirteen percent of NHL pts were transformed disease. Both groups had similar percentage of pts with central nervous system (CNS) lymphoma (~ 5%). Conditioning regimens varied based on lymphoma type: most of the HL/aggressive lymphomas: Etoposide+Melphalan (ML), CNS lymphoma: Thiotepa based regimen, and MCL Cytarabine + ML+/- Total Body Irradiation. The majority (83%) were treated for R/R disease, while 17% received it as first-line treatment. Prior to transplant, 76% of pts were in CR. Median follow-up was 38 months. Median OS was not reached for Group A, and 73 months for Group B. Five year OS were 82% and 74% respectively (p = 0.05). Median PFS was 75.2 months for Group A and 43.0 months for Group B, with 5-year PFS of 54% and 47% respectively (p = 0.2). Twenty percent of pts died during follow-up, with only 4% being NRM. From the entire cohort 3% of patients died within 100 days post-transplant, with no difference between groups. Three pts died within 100 days of ASCT with 2 deaths from sepsis (Group A) and 1 death from Respiratory failure (Group B). Common transplant-related toxicities did not differ significantly between groups (figure 1). Group B had significantly higher rates of Renal (7%vs 18%), Respiratory (16% vs 6%), and Metabolism abnormalities (14% vs 5%) (p = 0.021-0.028). Group B needed more blood product transfusions by 100 days post-transplant: Packed Cells (mean) 1.7 vs 1.1 units (p 0.08), Platelets (mean) 3 vs 1.9 units (p 0.002). Group B had a longer average length of stay 18 days vs. 14 days (p &amp;lt; 0.001). About 6% of pts required ICU admission, and 4% were discharged to rehabilitation/long-term care facilities, with no group differences. Conclusions: The study concludes that ASCT can be safely performed in appropriately selected elderly pts. TRM rates were not significantly higher in older compared to younger pts with lymphoma. However, older pts did experience higher rates of specific toxicities including renal failure, pulmonary complications, metabolism abnormalities, longer hospital stays, and increased transfusion requirements. In the multivariate analysis, older pts exhibited shorter OS, influenced by lymphoma type and treatment response. Further research is needed to develop risk stratification and geriatric assessments to improve toxicity prediction in elderly pts undergoing ASCT.

Anemia and Transfusion Dependency Are Important Prognostic Factors for Overall Survival in Patients with Myelofibrosis: Results of a Real-World Analysis of Medicare Patients

Introduction: Anemia is a hallmark feature of myelofibrosis (MF) and causes many patients (pts) to require red blood cell transfusions. Both anemia and transfusion dependency have been associated with decreased survival in pts with MF. The purpose of this study was to assess the relationship between anemia severity and transfusion dependency on overall survival (OS) among pts with MF in the Medicare population. Methods: This retrospective cohort study used the Medicare fee-for-service database to identify pts with a diagnosis of MF between January 1, 2012, and December 31, 2020. Study inclusion criteria were as follows: (1) ≥1 inpatient or ≥2 outpatient claims for MF (on separate dates &amp;lt;90 days apart; the earliest appearance of MF was set as the MF diagnostic index date [MFDID]); (2) 12 months of continuous enrollment preceding (baseline) and 6 months of continuous enrollment following (follow-up) the MFDID; (3) absence of Janus kinase inhibitor therapy during the 12-month baseline period; (4) absence of polycythemia vera, essential thrombocythemia, or another primary cancer other than basal and squamous cell skin carcinoma during the baseline period; and (5) absence of participation in a clinical trial. Transfusions were assessed over a 180-day landmark period following anemia index date (AID; set to the earliest evidence of anemia, unless it occurred during the 100 days prior to the MFDID, in which the AID was set to the MFDID), and pts were stratified into 3 subcohorts: transfusion independent (TI; no transfusions), transfusion dependent (TD; ≥6 transfusion claims on 6 separate days over any 12-week window), or transfusion requiring (TR; received transfusion claims but did not meet TD criteria). A subset of pts were identified as having anemia based on medical claims from the Medicare fee-for-service database or laboratory test results from the Prognos Biomarker and Laboratory Database ≤100 days before and any time after the MFDID, with severity subcohorts graded based on hemoglobin levels: mild (10 to &amp;lt;12 g/dL), moderate (8 to &amp;lt;10 g/dL), or severe (&amp;lt;8 g/dL) disease. OS from the MFDID was assessed for all pts using Kaplan-Meier analyses, with log-rank tests used to determine statistically significant differences among the transfusion dependency and anemia severity subcohorts. Results: A total of 1749 pts qualified for the transfusion cohorts: 980 were TI, 559 were TR, and 210 were TD. Mean age was 74.8 years, 47.9% were male, and 81.7% were White. Results of Kaplan-Meier analyses showed a median OS of 44.1 months (95% CI, 39.8-48.5 months) for the overall transfusion sample and 62.6 months (95% CI, 57.8-68.2 months) for the TI cohort, 29.0 months (95% CI, 25.9-32.9 months) for the TR cohort, and 22.6 months (95% CI, 20.1-28.1 months) for the TD cohort ( P&amp;lt;.001) (Figure A). A total of 265 pts with corresponding laboratory testing data qualified for the anemia cohorts: 128 were mild, 99 were moderate, and 38 were severe. Mean age was 73.6 years, 47.5% were male, and 79.6% were White. Results of Kaplan-Meier analyses showed a median OS of 64.3 months (95% CI, 56.5-76.9 months) for the overall anemia sample and 89.8 months (95% CI, 72.9 months-not calculable) for the mild cohort, 58.9 months (95% CI, 40.8-69.1 months) for the moderate cohort, and 20.6 months (95% CI, 15.9-49.4 months) for the severe cohort ( P&amp;lt;.001) (Figure B). Conclusions: These results demonstrate that dependency on transfusions, increasing transfusion requirements, and greater anemia severity are each negative prognostic factors for OS among Medicare fee-for-service pts with diagnosed MF. Therapies that reduce transfusion dependency and anemia severity may aid in improving health outcomes and prolong survival in pts with MF. Figure. Kaplan-Meier Curves of Overall Survival in Transfusion (A) and Anemia (B) Subcohorts, Calculated from the Myelofibrosis Diagnostic Index Date

Applying the Novel EHA/EBMT Grading System for Icaht Following CAR-T Therapy: Comparative Incidence across Disease Entities and Association with Infections and Mortality

Background: Hematological toxicity is a frequent side effect of CAR-T therapy and predisposes for severe infectious complications. Recently, the EHA/EBMT consensus grading for Immune Effector Cell Associated HematoToxicity (ICAHT) was developed ( Rejeski et al. Blood 2023). In contrast to existing grading systems such as the CTCAE, the novel ICAHT grading integrates both the depth and duration of neutropenia. We hypothesized that ICAHT severity is associated with key clinical sequelae such as transfusion requirements, hospitalization, severe infections, and adverse treatment outcomes. Methods: We applied the novel grading of early ICAHT (day 0-30) to a multicenter retrospective real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR T-cells for relapsed/refractory B-cell malignancies (334 large B-cell lymphoma [LBCL], 112 multiple myeloma [MM], 103 mantle cell lymphoma [MCL]) across twelve international sites (Germany, France, Spain, USA). Hematotoxicity endpoints included the total cumulative duration of severe neutropenia (ANC &amp;lt;500/µL, day 0-60) and phenotypes of neutrophil recovery ( Rejeski et al. Blood 2021). Infections were studied until day +90 after CAR-T and were graded on a 5-grade scale as mild, moderate, severe, life-threatening, or fatal. Non-relapse mortality (NRM) was defined as death following CAR-T without evidence of relapse or progression. Kaplan-Meier estimates of progression-free (PFS) and overall survival (OS) were compared using log-rank test. Results: Our study cohort included 424 patients without severe ICAHT (absent or grade 1-2) and 125 patients with severe ICAHT (grade 3-4). The distribution of mild (1°), moderate (2°), severe (3°) and life-threatening (4°) ICAHT was 36%, 29%, 17%, and 5%. Seventy patients (13%) did not develop ICAHT of any grade. When comparing ICAHT grades across disease entities, we noted a numeric trend towards increased severe ICAHT in MCL compared to LBCL or MM patients (Grade ≥3: 28% vs. 23% vs. 15%). Patients that subsequently developed severe ICAHT displayed elevated serum inflammatory markers and pronounced cytopenia at baseline - reflected by increased CAR-HEMATOTOX scores (median 3 vs. 1, p&amp;lt;0.0001). On multivariate binary logistic regression, co-stimulatory domain (CD28z), low platelet count, low ANC, low hemoglobin, increased serum ferritin, and the presence of bone marrow infiltration were independent risk factors for severe ICAHT. We noted a strong positive correlation between ICAHT severity and the cumulative duration of severe neutropenia (r=0.92, p&amp;lt;0.0001). The aplastic phenotype of neutrophil recovery was enriched in patients with grade 3 (73%) and especially grade 4 ICAHT (100%). Severe ICAHT was also associated with coincident multilineage cytopenias, resulting in increased transfusion requirements for both platelets (85% vs. 21%, p&amp;lt;0.0001) and red blood cells (86% vs. 41%, p&amp;lt;0.0001). In terms of management of hematotoxicity, the severe ICAHT group more commonly received G-CSF (72% vs. 44%, p=0.01), TPO mimetics (12% vs. 2%, p&amp;lt;0.0001) and hematopoietic stem cell boosts (6% vs. 0.2%, p&amp;lt;0.0001). Importantly, patients with severe ICAHT displayed a significantly increased rate of severe infections (49% vs. 13%, p&amp;lt;0.0001, Fig. 1a) and severe bacterial infections (36% vs. 8%, p&amp;lt;0.0001). This translated into a markedly increased 1-year NRM rate (14% vs. 4.5%, logrank p&amp;lt;0.0001, Fig. 1b), which was primarily attributed to fatal infections of fungal or bacterial origin. Of note, the ICAHT grading showed superior discrimination for severe infections (C-index 0.73, 95%CI: 0.67-0.78) compared to CTCAE grading (C-index 0.55, n.s.). Prolonged hospitalization was noted in case of severe ICAHT (median 21 vs. 16 days, p&amp;lt;0.0001) and intensive care admission was more common (23% vs. 4%, p&amp;lt;0.001). Finally, we observed inferior PFS (1-year PFS 35% vs. 51%, median 4 vs. 14 months, p&amp;lt;0.0001) and inferior OS (1-year OS 52% vs. 73%, median 12 months vs. not-reached, p&amp;lt;0.0001) in the patients that developed severe ICAHT. Conclusions: These data highlight the clinical relevance of the novel EHA/EBMT ICAHT grading system. Importantly, ICAHT severity was closely associated with transfusion dependence, increased infection incidence, and adverse treatment outcomes with high NRM. Taken together, these findings argue for reporting ICAHT grades in clinical trials evaluating established and novel CAR constructs.

Severe hypocalcemia at admission is associated with increased transfusion requirements: A retrospective study in a level 1 trauma center

IntroductionIn recent years, hypocalcemia has been added to the “lethal triad” of the trauma patient, thus constituting the “lethal diamond”. Nevertheless, its proper role remains debated. The aim of this study is to evaluate the association between severe hypocalcemia at admission and 24 h- transfusion requirements in severe trauma patients in a level 1 trauma center. Study design and methodsIn a monocentric retrospective observational study from January 2015 to May 2021, 137 traumatized adult patients transfused within 24 h after hospital admission was included in the study. The threshold for severe hypo ionized calcemia was ≤ 0.9 mmol/L. Results137 patients were included in the study, 23 presented with severe hypo-iCa at admission, 111 moderate hypo-iCa (0.9–1.2 mmol/L) and 3 normal iCa (≥ 1.2 mmol/L). Patients with severe hypo-iCa at admission had higher severity scores (SAPSII 58 IQR [51–70] vs. 45 IQR [32–56]; p = 0.001 and ISS 34 IQR [26–39] vs. 26 IQR [17–34]; p = 0.003). 24 h-transfusion requirements were greater for patients with severe hypo-iCa, regardless of the type of blood products transfused. There was a significant negative correlation between admission iCa and 24 h-transfusion (r = −0.45, p < 0.001). The difference in mortality was not significant between the two groups (24 h mortality: 17 % (4/23) for severe hypo-iCa vs. 8 % (9/114) for non-severe hypo-iCa; p = 0.3). DiscussionThis study highlights the high prevalence of severe hypocalcemia in trauma patients and its association with increased 24 h- transfusion requirements.

Red blood cell alloimmunization in myelodysplastic syndromes: Associations with sex, DAT-positivity, and increased transfusion needs.

Many patients with myelodysplastic syndromes (MDS) need repeated red blood cell transfusions which entails a risk of immunization and antibody formation. Associations between alloantibodies, autoantibodies and increased transfusion requirements have been reported, but their relationship remains unclear. In this study, we analyzed factors potentially associated with red blood cell alloimmunization, as well as changes in transfusion intensity and post-transfusion hemoglobin increments. In a retrospective cohort study, we linked Swedish MDS patients diagnosed between 2003 and 2017 to transfusion and immunohematology data. Potentially associated factors were analyzed using Cox proportional hazards regression. The transfusion rate after detected alloimmunization was analyzed using a fixed effects Poisson regression. Post-transfusion hemoglobin increments before and after alloimmunization were compared using a mixed effects regression. Alloantibodies following MDS diagnosis were detected in 50 out of 429 patients (11.7%). Female sex and a positive direct antiglobulin test (DAT) were independently associated with alloimmunization, with hazard ratios of 2.02 (95% confidence interval [CI] 1.08-3.78) and 9.72 (95% CI, 5.31-17.74), respectively. The transfusion rate following alloimmunization was increased with an incidence rate ratio of 1.33 (95% CI, 0.98-1.80) and the post-transfusion hemoglobin increment after alloimmunization was 1.40 g/L (95% CI, 0.52-2.28) lower per red blood cell unit (p = .002) compared to before alloimmunization, in multivariable analyses. Alloimmunization against blood group antigens was associated with sex, DAT-positivity, increased transfusion needs, and lower post-transfusion hemoglobin increments. These findings warrant further investigation to evaluate the clinical significance of up-front typing and prophylactic antigen matching in patients with MDS.

OA4‐AM23‐MN‐12 | Use of Low‐Dose Platelets Does Not Increase Transfusion Requirements During Major Cardiac Surgeries

OA4‐AM23‐MN‐12 | Use of Low‐Dose Platelets Does Not Increase Transfusion Requirements During Major Cardiac Surgeries

Outcomes and Predictors of Morbidity after Carotid Body Tumor Resection

Carotid body tumors (CBTs) are uncommon neuroendocrine tumors at the carotid bifurcation treated with resection. The goal of this study was to examine patient outcomes after CBT resection and establish predictors of morbidity. Patients undergoing CBT resection were identified from the National Surgical Quality Improvement Program (NSQIP) database over 11years. Demographics, past medical history, preoperative labs, procedural details, morbidity and mortality were recorded. Multivariable logistic regression (MLR) analysis was performed to determine independent predictors of morbidity. From 2010 to 2020, 668 CBT resections were identified. The majority of patients were female (65%) and White (72%) with a mean age of 56 (standard deviation [SD]±16). Average body mass index (BMI) was 29.9 (SD±7.1). Arterial resection occurred in 81 patients (12%). 6% of patients experienced morbidity, most commonly re-operation (2.4%). Morbidity was more common in patients with higher BMI (33.1 vs. 29.7, P=0.005), chronic obstruction pulmonary disease (10% vs. 1.9%, P=0.012), higher American Society of Anesthesiologists (P=0.005), and lower albumin (3.7 vs. 4, P=0.016). Morbidity was not increased with arterial resection (P=1) or based on length of operation (P=0.169). Morbidity did not impact mortality (P=0.06) though led to longer length of stay [LOS] (8days vs. 2.4, P<0.001). On MLR, preoperative BMI was the only risk factor for morbidity (odds ratio 1.06, 95% confidence interval 1.02-1.1, P=0.005). CBT resection is very well tolerated with low stroke rates, morbidity, and mortality. Arterial resection leads to increased transfusion requirements and LOS but did not increase stroke rates, mortality, or overall morbidity. Within the NSQIP database, preoperative BMI was the only predictor of postoperative morbidity, which leads to significantly longer LOS.

Predictors of mortality and transfusion requirements in venoarterial extracorporeal membrane oxygenation patients.

The aim of this study was to evaluate the prognostic impact of variables, including thrombocytopenia and the amount of platelet transfusion, for predicting survival in venoarterial extracorporeal membrane oxygenation (ECMO) recipients. Additionally, we aimed to identify the predictors of increased transfusion requirement during venoarterial ECMO support. All patients who received venoarterial ECMO between December 2008 and March 2020 were retrospectively analyzed. Univariate and multivariate Cox regressions were used to evaluate in-hospital mortality according to variables including thrombocytopenia and daily average of platelet concentrate transfusion. Stepwise multiple linear regression analysis was used to identify independent predictors for transfusion requirements. Analysis of 218 patients demonstrated severe thrombocytopenia as an independent predictor of in-hospital mortality (hazard ratio = 2.840, 95% CI: 1.593-5.063, P < .001), along with age, pre-ECMO cardiac arrest, and pH. In contrast, the amount of platelet transfusion was not associated with in-hospital mortality. Multiple variables, including the type of indication for ECMO were associated with transfusion requirements. Our findings identified severe thrombocytopenia as an independent prognostic factor of in-hospital mortality. However, daily average platelet transfusion was not associated with survival outcomes. Additionally, our study identified predictive variables of increased transfusion requirements.

952 The Use of Cell-Salvage in Periprosthetic Femur Fractures: A Cheaper and Safer Alternative?

Abstract Aim Periprosthetic femur fractures (PFF) are becoming increasingly frequent due to an ageing population and growing number of arthroplasties. PFF revision surgery is associated with significant peri-operative blood loss and higher transfusion requirements. There are few strategies to reduce rates of transfusion. One of which is the use of cell-salvage. The aim of this study was to determine whether cell salvage should be routinely implemented during PFF revision surgeries. Method All admission with PFF were retrospectively reviewed over a period of 18 months. Data points including patient demographics, admission/operation dates, fracture site, anticoagulation status, pre/post-op Hb and number of transfusions were collected. Results There were a total of 38 PFF. Average age was 83.4 years with admission Hb 11.65g/dl. Mean time for operation was 2.9 days. 56% of total hip replacement PFF received a blood transfusion post-operatively with an average of 2.6 units per patient. 100% of total knee replacement PFF received a post-operative transfusion with an average of 1.6 units per patient. Of note there was no increased transfusion requirements for patient on anticoagulation (Warfarin/DOAC). Conclusions We identified that &amp;gt;50% of PFF required a post-op transfusion. The cost of 1 unit of RBC locally was found to be £145.99. The average cost of a cell salvage filter is £100 per patient. Considering the above and the well-known risk of allogenic red blood cell transfusion, it was concluded that the routine use of cell salvage could be a cheaper and safer alternative to allogenic red blood cell transfusion.

Impact of accidental hypothermia in trauma patients: A retrospective cohort study

BackgroundTrauma patients with hypothermia have substantial increases in mortality and morbidity. In severely injured patients, hypothermia is common with a rate up to 50% in various geographic areas. This study aims to elucidate the incidence, predictors, and impact of hypothermia on outcomes in severely injured patients. MethodsThis was a retrospective cohort study which included trauma patients with an Injury Severity Score (ISS) ≥ 16 admitted to a level 1 trauma center in the Netherlands between January 1, 2015 and December 31, 2021. Primary outcome was incidence of hypothermia on arrival at the emergency department. Factors associated with hypothermia were identified. Secondary outcomes were transfusion requirement, mortality, and intensive care unit (ICU) admission. Logistic regression analysis was used to identify associations. ResultsA total of 2032 severely injured patients were included of which 257 (12.6%) were hypothermic on hospital arrival. Predictors for hypothermia on hospital arrival included higher ISS, prehospital intubation, cervical spine immobilization, winter months, systolic blood pressure (SBP) < 90 mmHg and Glasgow Coma Scale (GCS) ≤ 8. Hypothermia was independently associated with transfusion requirement (OR, 2.68; 95% CI, 1.94 – 3.73; p < 0.001), mortality (OR, 2.12; 95% CI, 1.40 – 3.19; p < 0.001) and more often ICU admission (OR, 1.81; 95% CI, 1.10 – 2.97, p = 0.019). ConclusionsIn this study, hypothermia was present in 12.6% of severely injured patients. Hypothermia was associated with increased transfusion requirement, mortality, and ICU admission. Identified predictors for hypothermia included the severity of injury, intubation, and immobilization, as well as winter season, SBP < 90 mmHg, and GCS ≤ 8.

A retrospective validation of ROTEM algorithms for detecting hyperfibrinolysis demonstrates poor agreement for prediction of in-hospital mortality and transfusion requirement in a general, non-cardiac, surgical population

IntroductionHyperfibrinolysis diagnosed on Rotational Thromboelastography (ROTEM) is associated with increased transfusion requirements and mortality in trauma. The diagnosis and significance of hyperfibrinolysis in a mixed, non-cardiac, general surgical population has not been investigated. We aimed to measure agreement between four ROTEM algorithms for diagnosing hyperfibrinolysis and transfusion requirements and mortality in general surgical patients. These algorithms mostly incorporate measures of early or late clot amplitude reduction on the Extrinsic Clotting Pathway Test with Tissue Factor (EXTEM) channel. MethodFour hospital administrative data sets were linked from 2019 to 2022. Adults >18 years were included if a ROTEM was performed during their surgery (intraoperative period) or within 24-h of the surgery completion (postoperative period). The four hyperfibrinolysis criteria were applied to the ROTEM data and assessed for their agreement, intraoperative and postoperative transfusion requirements and in-patient mortality. ResultsWe linked 933 ROTEMs to 558 patient-procedures. One algorithm identified hyperfibrinolysis on only three patients so was excluded. Agreement between the remaining three was slight (Cohens Kappa 0.18 (p < 0.001)) with hyperfibrinolysis diagnosed between 22 and 69 % of the procedures. The association between hyperfibrinolysis diagnosis and intraoperative or postoperative transfusion requirement was inconsistent between the criteria. However, an algorithm put forward by Goerling et al. was more often associated with transfusion requirement and inpatient mortality. DiscussionThe poor agreement between criteria suggests that some ROTEM criteria may not transfer directly to general surgical patients. Future research should focus on optimising hyperfibrinolysis cut-off values to update algorithms for bleeding general surgical patients.

Bivalirudin Superiority in Pediatric Berlin Hearts: Too Early to Draw Conclusions?

To the Editor: We commend Freniera et al. for their single-center retrospective review involving 31 pediatric Berlin Heart Ventricular Assist Devices anticoagulated with either bivaluridin or unfractionated heparin (UFH).1 We would like to highlight the need for robust performance assessment of the effects of these systematic anticoagulants, particularly during mechanical support. As a measure of inhibition of a single enzyme (activated coagulation factor X), the anti-factor-Xa (anti-Xa) assay represents a more direct measure of UFH activity than the activated partial thromboplastin time (aPTT), with reduced variability and minimal interference from biologic factors, such as lupus anticoagulants or elevated factor VIII.2 As such, the College of American Pathologists defines therapeutic reference ranges as direct measurements of heparin activity, such as anti-Xa. This is important, as divergent assay occurrence rates of up to 40%–60% may exist between groups whose systemic anticoagulant is titrated upon functionally different assays.3 The greater chest tube output and trend toward increased transfusion requirement in those receiving UFH may be explained by more intense anticoagulation while the rates of elevated D-dimer and plasma-free hemoglobin may be reflective of less vigorous anticoagulant effect. Corroborating this postulated causation, Freniere et al. found no differences in time to reach therapeutic aPTT between groups (5.7 vs. 12.6 hours, p = 0.149) despite profound variance when comparing bivalirudin titrated with aPTT and UFH managed with anti-Xa, which is derived from the markedly prolonged time to therapeutic range for UFH (69.5 hours).1 Accordingly, the concordance between aPTT and anti-Xa was found to be moderate (r = 0.63). Additionally, the impact of kidney impairment on bivalirudin pharmacokinetics needs to be accounted for. Although it remains impossible to determine the presence, nor the functional impact, of disparate anticoagulant intensities between groups with the data provided in this study, the lack of elucidation necessitates consideration before drawing definitive conclusions. Although we share the authors passion and enthusiasm for the administration of bivalirudin in the context of mechanical circulatory support due to the ease of dosing, the potential promise of enhanced outcomes,4 and favorable cost profile,5 caution must be urged before these advantages can be translated into the causation of yet to be determined superiority of clinical outcomes. We would also like to caution on the authors introduction of a term so-called VAD-itis seemingly on the basis of retrospective record entry or receipt of immunosuppressants. Although introducing foreign surfaces with mechanical devices triggers the inflammatory system, this “condition” should be identified via actions and judgment, not by any isolated immunological variable. For example, c-reactive protein was not different between groups.1 Considering that biofilm is formed, and the immune system evolves over time, an analysis of simple averages is of little value, even for the highly nonspecific c-reactive protein. While the authors discussion focused on methylprednisone, aspirin is also a potent immunomodulator whose dosing differed significantly between groups. However, to imply that higher aspirin dosing in bivalirudin group is related to more “VAD-it is” is an example of action taken as evidence, while not evidence or causation of any sort.

D39. Free Tissue Transfer to the Lower Extremity in the Setting of Thrombocytosis and the Role of Anti-platelet Therapy: A Retrospective Review

PURPOSE: In patients undergoing lower extremity (LE) free tissue transfer (FTT), preoperative thrombocytosis (PT) is associated with an increased risk of complications in select patient populations. We sought to assess the feasibility of performing LE FTT in atraumatic patients with PT, and whether antiplatelet (AP) therapy on the day of surgery (DOS) affects outcomes. METHODS: A retrospective review of patients with PT who underwent LE FTT between 2011-2022 was performed. Patients were categorized based on AP therapy on the DOS. Outcomes included transfusion requirements, postoperative flap-related complications (thrombosis, hematoma, return to the operating room), rates of flap success, limb salvage and ambulatory status. RESULTS: Of the 279 patients who underwent LE FTT, 65 (23.3%) had PT; of which, 32 (49.2%) received DOS AP therapy (“AP group”). Patients in the AP group were older (58.9 vs. 51.6 years, p=0.014), and had a greater representation of diabetes mellitus (87.5% vs. 57.6%, p=0.007) and calcified vessels (62.5% vs. 12.1%, p&lt0.0001). Average intraoperative and postoperative transfusion volumes were significantly higher in the AP group (p&lt0.05). Flap success rate was 96.9% (n=63). Rates of postoperative thrombosis were similar (9.4% vs. 6.1%, p=0.672), as was hematoma incidence (9.4% vs. 3.0%, p=0.287). At mean follow-up of 21.6 + 21.5 months, limb salvage and ambulatory rates were 75.4% (n=49) and 78.5% (n=51), respectively, and mortality rate was 7.7% (n=5). CONCLUSION: PT is not an absolute contraindication to LE FTT. DOS AP therapy may be protective in comorbid patients, but must be weighed against possible short-term bleeding, suggested by increased transfusion requirements.

Evaluation of gastrointestinal complications in Egyptian patients after autologous stem cell transplantation using melphalan-based regimens

BackgroundAutologous stem cell transplantation (ASCT) is a curative treatment for patients with hematological malignancies. Melphalan either alone or in combination with other chemotherapeutic agents is a widely used pre-transplant conditioning regimen with known gastrointestinal (GI) complications. We retrospectively evaluate the incidence and severity of GI toxicities, the possible risk factors, and their impact on transplant outcomes in 47 patients who received ASCT using melphalan-based conditioning.ResultsMedian age was 50 years. Among our patients, 48.9% received melphalan at 200 mg/m2. Mucositis was developed in 93.6% of patients, nausea in 87.2% and grade 2 vomiting in 36.2% of patients. Grade 3 diarrhea was detected in 42.6%. Severe GI toxicities were associated with significantly delayed engraftment, longer hospital stay, and increased transfusion requirements but overall survival (OS) and transplant-related mortality (TRM) were not affected by the severity of GI symptoms.ConclusionDespite using prophylactic and supportive care, some patients developed severe GI complications following different doses of melphalan with a negative effect on some transplant outcomes. Melphalan dose or disease type was not identified as a risk factor for severe GI toxicity. Additional larger prospective studies with higher doses, different formulations, and better prophylactic measures are warranted to evaluate potential risk factors and their impact on GI toxicities.