Reduce Transfusion Requirements Research Articles

Tranexamic Acid is Associated with Reduced Blood Loss and Transfusion Requirement in Pediatric Midface Reconstruction

BackgroundMidface reconstruction poses challenges due to significant blood loss and difficulty in achieving intraoperative hemostasis, often necessitating blood transfusions. Various agents, most notably tranexamic acid (TXA), have been utilized intraoperatively to mitigate this risk of bleeding and transfusion-related complications. PurposeThe study purpose was to measure the association of TXA with blood loss and transfusion requirements during craniofacial procedures involving the midface. Study design, setting, sampleThis project was designed as a retrospective cohort study. Patients who underwent midface reconstruction at Children's Hospital Los Angeles (CHLA) between 2010 and 2023 were included, and a retrospective chart review was conducted. Independent variableThe independent variable was weight-adjusted TXA exposure divided into two groups: subjects who received TXA pre- and intraoperatively and those that did not. Main Outcome VariablesThe main outcome variables were weight-adjusted intraoperative blood loss and transfusion requirements. Secondary outcomes included intra- and postoperative complications and length of stay. CovariatesDemographic covariates included age at surgery, sex, weight, and syndromic status. Operative covariates covered the type of surgical approach and main procedure performed. Perioperative covariates included anesthesia time and operative time. AnalysesParametric and non-parametric variables were analyzed using independent t-test and Wilcoxon rank-sum test, respectively. Chi-squared analysis was used to analyze categorical variables, and multivariable linear regressions were performed. A p-value of less than 0.05 was considered statistically significant. ResultsA total of 80 patients underwent midface reconstruction surgery, 37 (46.3%) of whom received TXA and 43(53.7%) did not. The mean age at surgery was 8.7±3.8 years in the TXA cohort and 11.6±5.1 years in the non-TXA cohort (p=0.02). Multivariable regression analysis further demonstrated a statistically significant association between the administration of TXA and both reduced blood loss (coefficient -0.14 [95% CI -0.20 to -0.07], p<0.01) as well as reduced transfusion requirement (coefficient -0.14 [95% CI -0.19 to -0.08], p<0.01). There was no increased risk of complications, such as thromboembolic events or seizures, in patients who were administered TXA (p=0.14). Conclusion and RelevanceTXA is likely a valuable adjunct for improving intra- and postoperative outcomes of craniofacial procedures involving the midface.

Should viscoelastic testing be a standard point-of-care test on all intensive care units?

Viscoelastic tests (VETs) have transformed assessment of haemostasis and transfusion practices in trauma, cardiac and liver transplantation centres. Impaired haemostasis is a common problem on the general intensive care unit (ICU), but routine use of VETs is rare. We have accordingly reviewed the evidence to determine whether there is evidence to support the use of VETs as a standard point of care test on all ICUs in assessing and managing patients. The benefits of using VETs in the management of major haemorrhage, namely faster identification of a coagulopathy, in particular early detection of fibrinolysis, and reduced transfusion requirements for blood products have been seen in the general ICU. Validation of treatments algorithms is now required to standardise practice. There is also emerging evidence to support the use of VETs to guide urgent treatment decisions in patients with a coagulopathy or in patients taking anti-coagulants or anti-platelet therapies. We recommend that departments independently review the feasibility of setting up a viscoelastic point of care service which considers the applicability to their patient cohort, the financial cost and the personnel required.

Effective Pediatric Blood Management in Craniosynostosis Surgery: A Long-Term Update.

Blood transfusion is common in cranial vault surgery, and protocolized efforts to minimize transfusion have been reported in recent years. This study assesses the long term, prospective outcomes of a pediatric blood management protocol for the cranial vault reconstruction (CVR) population. Data from a retrospective control cohort and a prospective cohort employing a protocol for preoperative hematologic optimization of patients undergoing CVR from January 2015 to October 2023 was reviewed. Preoperative hemoglobin (Hgb) determined the preoperative protocol. Intraoperative tranexamic acid (TXA) and/or aminocaproic acid, cell-saver technology, and postoperative iron or erythropoietin alfa supplementation were also used in the protocol. For statistical analysis, P<0.05 was deemed significant. The cohort consisted of 194 successive patients (20 control and 174 treatment). Age, sex, and weight were not significantly different between groups. Mean postoperative Hgb was significantly higher in the control group (P<0.01). No difference was observed in Hgb at discharge between control and treatment groups. Mean estimated blood loss, volume of intraoperative packed red blood cells, rate of packed red blood cell transfusion, and mean total transfusion volume during hospitalization were significantly higher in the control group compared with the treatment group (P<0.01). Mean length of stay did not differ between groups. Efforts to optimize blood management in the CVR population are critical. This prospective study represents a robust and reproducible protocol for pediatric blood management with significant reductions in transfusion requirements.

The effect of whole blood resuscitation on in-hospital mortality: A propensity score weighted analysis of patients treated at a Level I trauma center.

Whole blood (WB) transfusion, compared with blood component therapy (CT), has been shown to have superior outcomes in the military population. However, whether this translates to the civilian population remains understudied. This study sought to determine the effect of WB on short-term in-hospital outcomes. This retrospective cohort study included trauma patients at a Level I trauma center who received either WB or CT upon massive transfusion protocol activation between January 2021 and June 2023. The primary outcome was in-hospital mortality, and secondary outcomes included 24-hour mortality, 7-day mortality, 30-day mortality, trauma-induced coagulopathy, and the number of transfusion events required. The effect of transfusion type on patient outcomes was evaluated using a propensity-weighted modified Poisson regression. Of 1,027 massive transfusion protocol-activated patients, 480 (46.8%) received any WB. The propensity score weighting balanced the covariate distribution between the transfusion groups. Significant effect modification (p < 0.05) by injury type (blunt vs. penetrating) on mortality outcomes was observed. Compared with CT recipients, penetrating trauma patients who received WB had a significantly lower adjusted risk of in-hospital (risk ratio [RR], 0.36; 95% confidence interval [CI], 0.15-0.89), 7-day (RR, 0.37; 95% CI, 0.15-0.94), and 30-day (RR, 0.36; 95% CI, 0.15-0.89) mortality but not significantly different 24-hour mortality (RR, 0.39; 95% CI, 0.15-1.00; p = 0.05). An elevated risk of trauma-induced coagulopathy was observed among WB recipients than CT recipients with blunt trauma (RR, 1.59; 95% CI, 1.07-2.36) but not among patients with penetrating injury (RR, 0.65; 95% CI, 0.30-1.40). Compared with CT recipients, WB recipients had reduced transfusion rates for both penetrating (RR, 0.59; 95% CI, 0.36-0.95) and blunt-related injuries (RR, 0.73; 95% CI, 0.58-0.91). The effect of WB on in-hospital mortality is modified by injury type, suggesting the need to consider penetrating injury as an important indication for WB resuscitation. In addition, WB reduces transfusion requirements across both injury types, decreasing patient exposure to transfusion events. Therapeutic; Level III.

Momelotinib versus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: an efficacy/safety analysis in the Japanese subgroup of the phase 3 randomized SIMPLIFY-1 trial

Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.

Risk of bleeding after abdominal paracentesis in patients with chronic liver disease and coagulopathy: A systematic review and meta-analysis.

Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post-abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random-effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I 2, τ2 statistics, and P-value. Eight studies were included for review. Six studies reported incident events of post-abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15-0.69%). The mean values for pre-procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0-0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure-related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements.

The Impact of Tranexamic Acid on Blood Loss Management in Primary Total Knee Arthroplasty: A Comprehensive Review.

Total knee arthroplasty (TKA) is a widely performed surgical procedure to restore function and relieve pain in patients with advanced knee arthritis. One of the key challenges in TKA is managing perioperative blood loss, which can lead to complications such as postoperative anemia and the need for blood transfusions. Tranexamic acid (TXA), an antifibrinolytic agent, has shown promising results in reducing blood loss and transfusion requirements in various surgical settings, including TKA. This comprehensive review synthesizes current evidence regarding the efficacy and safety profile of TXA in primary TKA. Mechanistically, TXA functions by inhibiting the breakdown of fibrin clots, promoting hemostasis, and minimizing blood loss. Clinical studies evaluating TXA in TKA have consistently demonstrated significant reductions in blood loss parameters, including total blood loss, postoperative drain output, and transfusion rates. Key findings highlight the efficacy of TXA across different dosing regimens and administration routes, with minimal associated risks of thromboembolic events or adverse effects. Comparative analyses with other blood conservation strategies underscore TXA's superiority in reducing transfusion requirements and its cost-effectiveness in clinical practice. The review also discusses current clinical guidelines and recommendations for TXA use in TKA, emphasizing optimal dosing strategies and patient selection criteria. Future research directions include exploring the long-term outcomes of TXA administration and its impact on functional recovery, and refining protocols to enhance its efficacy and safety further. In conclusion, TXA represents a valuable adjunct in blood loss management during primary TKA, offering substantial benefits in patient outcomes, healthcare resource utilization, and cost-effectiveness. Continued research efforts are warranted to optimize its use and expand its applicability in orthopedic surgery.

INVESTIGATING THE RELATIONSHIP BETWEEN BLEEDING, CLOTTING, AND COAGULOPATHY DURING AUTOMATED PARTIAL REBOA STRATEGIES IN A HIGHLY LETHAL PORCINE HEMORRHAGE MODEL.

Background: Death due to hemorrhagic shock, particularly, noncompressible truncal hemorrhage, remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently, whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer. In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared with pREBOA due to more oscillatory flow. Methods: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 min of automated pREBOA, iREBOA, or no balloon support (control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., eight key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 min). Citrated kaolin heparinase assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between the iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R time: P < 0.001; K time: P < 0.001) and clot strength (MA: P = 0.01; G: P = 0.02) over the duration of the experiment. Conclusions: Despite observing acute differences in peak proximal pressures between the iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

#1171 Effect of methoxy polyethylene glycol-epoetin beta on delaying dialysis in anemic patients with Stage 4-5 chronic kidney disease

Abstract Background and Aims The optimal hemoglobin (Hb) target for treating anemia in pre-dialysis chronic kidney disease (CKD) remains controversial. This study investigates the efficacy and safety of methoxy polyethylene glycol-epoetin beta, in delaying the initiation of kidney replacement therapy (KRT), all-cause mortality, CKD progression, and quality of life in stage 4-5 CKD patients. It compares outcomes between patients targeting an Hb level of 10.5-11.5 g/dL versus 8.5-9.5 g/dL. Method This was a single-center, open-label, parallel-group randomized controlled trial. Patients with estimated glomerular filtration rates (eGFR) of 8-15 ml/min/1.73 m2, who had not yet started dialysis, were randomized into two groups based on different Hb targets (Group A: 10.5-11.5 g/dL, Group B: 8.5-9.5 g/dL). Methoxy polyethylene glycol-epoetin beta (MIRCERA®) was prescribed by a pre-specified protocol to achieve these Hb targets. Iron supplements were administered to maintain transferrin saturation &amp;gt;20% or serum ferritin &amp;gt;200 ng/ml. Primary outcomes included a composite of all-cause death and KRT initiation, with secondary outcomes encompassing eGFR slope, hospitalization incidence, blood transfusion necessity, and quality of life measured by the 36-Item Short Form Health Survey (SF-36). Results A total of 62 participants were randomized. The mean age was 64.0 years (SD ±16.0), with 51.6% being female. The mean estimated Glomerular Filtration Rate (eGFR) at enrollment was 12.1 ml/min/1.73 m2 (SD ±3.1). Group A had a significantly higher time-averaged Hemoglobin (Hb) level (10.5 g/dL, SD ±1.2) compared to 8.5 g/dL (SD ±0.9) in the control group (p &amp;lt; 0.001). There was no significant difference in the composite endpoint of all-cause death and Kidney Replacement Therapy (KRT) initiation between the two groups (Hazard Ratio [HR] 0.69; 95% Confidence Interval [CI] 0.32-1.50; p = 0.35, as shown in the Figure). The eGFR slope was similar in both groups (−2.54 vs. −2.53 ml/min/1.73 m2 per year, p = 0.9). Time-averaged ferritin, transferrin saturation, blood pressure, and dietary sodium/protein intake showed no significant differences. Participants in the lower Hb target group required more blood transfusions (11 vs 1 unit, Incidence Rate Ratio [IRR] = 0.075, 95% CI 0.002-0.517, p = 0.001). Rates of hospital admissions, and changes in SF-36 quality of life domains were comparable between the groups, as detailed in the Table. Conclusion The study indicates that using methoxy polyethylene glycol-epoetin beta to maintain a higher Hb target in anemic patients with stage 4-5 CKD does not significantly alter the rate of all-cause mortality, the initiation of KRT, and rate of eGFR decline compared to a lower Hb target. However, a higher Hb target may reduce the need for blood transfusions without adversely affecting the progression of CKD, hospitalization rates, or quality of life. These findings suggest that while higher Hb targets may not dramatically alter key clinical outcomes, they could offer benefits in reducing transfusion requirements, thus providing a more nuanced approach to managing anemia in late-stage CKD.

Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis.

Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.

Efficacy of human prothrombin complex concentrate in the treatment of warfarin overdose in patients receiving warfarin for mechanical heart valve replacement.

Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.

Thalidomide and Hydroxyurea in Transfusion-Dependent Thalassemia: Efficacy, Safety Profile and Impact on Quality of Life

Transfusion-dependent thalassemia (TDT) is a major public health concern in India, requiring regular transfusions for survival. There is also significant morbidity caused by iron overload and transfusion related infections. Novel therapies targeting fetal hemoglobin induction are the need of the hour in resource-poor institutions for patients where transplant is not feasible for various reasons. This single arm, non-randomised prospective trial evaluated the efficacy and safety of a combination of low dose thalidomide and hydroxyurea in TDT along with the impact on quality of life (QoL). It included 41 TDT patients, who failed a reasonable trial of hydroxyurea. Complete response (CR) was defined as transfusion independence and partial response (PR) denoted at least a 50% reduction in transfusion requirement. The rest were defined as non-responders (NR). The mean age of the cohort was 20.78 years (range 12–45 years). There were 13 males and 28 females. Nineteen (46.3%), 7 (17.1%), and 15 (36.6%) patients achieved CR, PR, and no response respectively. The overall response rate (CR + PR) was 63.4%. There was a significant increase in hemoglobin levels with decrement in transfusion burden and ferritin levels. There were no significant adverse reactions. No significant predictors of response were found including amongst genetic modifiers. It improved the health related QoL amongst responders. The combination of thalidomide and hydroxyurea appear safe and effective in the reduction in transfusion requirement of TDT patients. The judicious use of these drugs can improve the quality of life and pave the way for patients not eligible for a stem cell transplant.

Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies

BackgroundAnemia is a hallmark of critical illness, which is largely inflammatory driven. We hypothesized that the use of anti-inflammatory agents limits the development of anemia and reduces the need for red blood cell (RBC) transfusions in patients with a hyper-inflammatory condition due to COVID-19.MethodsAn observational cohort (n = 772) and a validation cohort (a subset of REMAP-CAP, n = 119) of critically ill patients with hypoxemic respiratory failure due to COVID-19 were analyzed, who either received no treatment, received steroids or received steroids plus IL-6 blocking agents. The trajectory of hemoglobin (Hb) decline and the need for RBC transfusions were compared using descriptive statistics as well as multivariate modeling.ResultsIn both cohorts, Hb level was higher in the treated groups compared to the untreated group at all time points. In the observational cohort, incidence and number of transfused patients were lower in the group receiving the combination treatment compared to the untreated groups. In a multivariate analysis controlling for baseline Hb imbalance and mechanical ventilation, receipt of steroids remained associated with a slower decline in Hb level and the combination treatment remained associated with a slower decline of Hb and with less transfusions. Results remained the same in the validation cohort.ConclusionImmunomodulatory treatment was associated with a slower decline in Hb level in critically ill patients with COVID-19 and with less transfusion. Findings point toward inflammation as an important cause for the occurrence of anemia in the critically ill.

Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Transfusion Therapy in HIV: Risk Mitigation and Benefits for Improved Patient Outcomes

Transfusion therapy is a pivotal aspect of healthcare, especially for individuals living with Human Immunodeficiency Virus (HIV). This comprehensive review aims to dissect the intricate landscape of transfusion therapy in HIV patients, emphasizing the delicate balance between risks and benefits to achieve enhanced patient outcomes. With advancements in blood safety measures and antiretroviral therapy (ART), navigating the complexities of transfusion therapy in HIV management becomes paramount for healthcare professionals. The review consolidates current knowledge and emerging trends, encompassing challenges, benefits, risks, and strategies to optimize transfusion therapy for improved patient care. The paper delineates key areas, including blood safety measures such as nucleic acid testing (NAT) and pathogen reduction technologies, emphasizing their role in ensuring safer blood products for transfusion in HIV patients. Furthermore, it explores the impact of HIV on hematological disorders, delving into transfusion-transmitted infections and strategies to mitigate these risks. Additionally, it scrutinizes the therapeutic benefits of transfusion therapy in managing hematologic complications in HIV, while addressing potential risks, including immune reactions and adverse effects. Optimizing transfusion therapy in HIV necessitates personalized approaches, considering the individual patient's HIV status, comorbidities, and specific transfusion needs. The role of ART in reducing transfusion requirements and associated risks is highlighted, alongside emerging trends like novel therapies and alternative transfusion practices. Keywords: Transfusion therapy, HIV, blood safety, antiretroviral therapy, risks, benefits, patient outcomes, transfusion-transmitted infections, personalized treatment, hematology, blood products

Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms

In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2–6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5–39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation.

Massive Transfusion/Hemorrhage Protocols Versus Goal-Directed Bleeding Management: Science Gone Eerie?

Key questions in bleeding management are “Why does my patient bleed?” and “How to fix it?” To answer the first question, the high negative predictive value of viscoelastic testing can be used to identify coagulopathic bleeding. Accordingly, goal-directed bleeding management (GDBM) guided by viscoelastic testing has been shown to be an effective and essential part of the second pillar of patient blood management (PBM) with the aim to improve patients’ outcomes and safety. Patient’s medical and drug history – with a focus on medication with oral anticoagulants and antiplatelet drugs – are important in emergency, urgent, and elective surgery. Furthermore, risk scores have been developed and validated for traumatic and obstetric hemorrhage and can be helpful tools to predict severe hemorrhage and the need for massive transfusion. Acidosis, hypocalcemia, anemia, and hypothermia (“diamond of death in trauma”) are important basic conditions for hemostasis and good predictors of coagulopathy and should be closely monitored by blood gas analysis and corrected in bleeding patients. Earlier time to hemostasis was associated with decreased mortality in trauma studies. Therefore, GDBM aims to stop the bleeding as soon as possible and avoid the main killers in blood transfusion: Transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-related immune modulation, and thrombosis. Thromboelastometry-guided bleeding management follows the concepts of Good Medical Practice and Precision Medicine. Here, rotational thromboelastometry (ROTEM)-guided bleeding management algorithms are using a stepwise approach based on the sequence “Treat first what kills first:” (1) Fibrinolysis management, (2) clot firmness management, (3) thrombin generation management, and (4) avoidance of hypercoagulability and thrombosis. Here, thromboelastometry can not only identify patients with hypercoagulability and increased risk of thrombosis but also ROTEM-guided bleeding management can avoid thromboembolic complications, too. This may support the idea of personalized antithrombotic therapy guided by viscoelastic testing in the postoperative period. Finally, PBM is not about blood transfusion: It is about patients’ outcomes. Accordingly, several meta-analyses based on more than 20 randomized controlled trials on the effect of viscoelastic testing-guided perioperative bleeding management did not only demonstrate a significant reduction in transfusion requirements but also a significant reduction in mortality and postoperative acute kidney injury. The reduction in postoperative acute kidney injury again has a significant impact on long-term survival. Accordingly, recent PBM guidelines recommend the implementation of viscoelastic testing-guided bleeding management algorithms with a 1B or 1A recommendation. This is also addressed in the World Health Organization policy brief about the urgent need to implement PBM in all member states in a timely manner. However, even if the number of national activities is increasing, there is still a long way to go.

Hemostatic effect of fibrinogen concentrate on traumatic massive hemorrhage: a propensity score matching study

BackgroundFibrinogen concentrate (FC) can be administered during massive transfusions to manage trauma-induced coagulopathy. However, its effectiveness in survival remains inconclusive due to scarce high-level evidence. This study aimed to investigate...

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial

Background and aimsGastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We aimed to investigate the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. MethodsThe study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least four red blood cell (RBC) units and/or parental iron infusions in the year preceding randomization. Patients were allocated (1:1) to 40mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least one octreotide injection or followed standard of care for at least one month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. ResultsWe enrolled 62 patients (mean age 72 years, 32 males) from 17 Dutch hospitals in the octreotide (n=31) and standard of care (n=31) groups. Patients required a mean number of 20.3 (SD 15.6) transfusion units and 2.4 (SD 2.0) endoscopic procedures in the year before enrolment. The total number of transfusions was lower with octreotide (11.0; 95% CI, 5.5–16.5) compared to standard of care (21.2; 95% CI, 15.7–26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4–18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3–1.5). ConclusionOctreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. ClinicalTrials.gov, NCT02384122.

Empiric Cryoprecipitate Transfusion in Patients with Severe Hemorrhage: Results from the US Experience in the International CRYOSTAT-2 Trial.

Hypofibrinogenemia has been shown to predict massive transfusion and is associated with higher mortality in severely injured patients. However, the role of empiric fibrinogen replacement in bleeding trauma patients remains controversial. We sought to determine the effect of empiric cryoprecipitate as an adjunct to a balanced transfusion strategy (1:1:1). This study is a subanalysis of patients treated at the single US trauma center in a multicenter randomized controlled trial. Trauma patients (more than 15 years) were eligible if they had evidence of active hemorrhage requiring emergent surgery or interventional radiology, massive transfusion protocol (MTP) activation, and received at least 1 unit of blood. Transfer patients, those with injuries incompatible with life, or those injured more than 3 hours earlier were excluded. Patients were randomized to standard MTP (STANDARD) or MTP plus 3 pools of cryoprecipitate (CRYO). Primary outcomes included all-cause mortality at 28 days. Secondary outcomes were transfusion requirements, intraoperative and postoperative coagulation laboratory values, and quality-of-life measures (Glasgow outcome score-extended). Forty-nine patients (23 in the CRYO group and 26 in the STANDARD group) were enrolled between May 2021 and October 2021. Time to randomization was similar between groups (14 vs 24 minutes, p = 0.676). Median time to cryoprecipitate was 41 minutes (interquartile range 37 to 48). There were no differences in demographics, arrival physiology, laboratory values, or injury severity. Intraoperative and ICU thrombelastography values, including functional fibrinogen, were similar between groups. There was no benefit to CRYO with respect to post-emergency department transfusions (intraoperative and ICU through 24 hours), complications, Glasgow outcome score, or mortality. In this study of severely injured, bleeding trauma patients, empiric cryoprecipitate did not improve survival or reduce transfusion requirements. Cryoprecipitate should continue as an "on-demand" addition to a balanced transfusion strategy, guided by laboratory values and should not be given empirically.