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Background: Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage., Objective: To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality., Design: A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken., Setting: Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA., Participants: Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion., Intervention: Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only., Main Outcome Measures: The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays)., Results: Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality ( n  = 1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; p  = 0.74)., Limitations: There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation., Conclusions: There was no evidence that early empiric administration of high-dose cryoprecipitate reduced the risk of death in unselected patients with traumatic haemorrhage. There was also no difference in adverse events. The cost-effectiveness of the intervention was similar to that of standard care., Future Work: Research to evaluate if fibrinogen replacement is more beneficial for selected patients, for example those with low fibrinogen blood levels, is needed, as is further exploration of whether there is a difference in outcome according to mechanism of injury., Trial Registration: This trial is registered as ISRCTN14998314., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/57/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 76. See the NIHR Funding and Awards website for further award information.

Introduction: Delays in promptly recognizing and appropriately managing hemorrhagic injuries contribute to preventable trauma related deaths nationwide. We sought to identify patient variables available at the time of emergency department arrival associated with meeting the critical administration threshold., Methodology: We conducted a trauma registry review from September 2016 to March 2020 of trauma team activations at The Ottawa Hospital, a Level 1 Trauma Center. Our primary outcome was the frequency of meeting the critical administration threshold. Secondary outcomes included time to critical administration threshold, 24-h all-cause mortality, and 30-day all-cause mortality. Multivariate logistic regression identified factors independently associated with meeting the critical administration threshold., Results: We assessed 762 patients, of which 78 (10.2%) met the critical administration threshold. The median time to critical administration threshold was 28.9 min. Mortality at 24 h occurred in 58 (7.6%) patients. Four variables available upon patient arrival predicted the critical administration threshold, including systolic blood pressure ≤ 90 mmHg (OR 6.6; 95% CI 3.7-12.0), Glasgow Coma Scale ≤ 8 (OR 5.9; 95% CI 3.2-10.6), heart rate ≥ 100 beats/minute (OR 4.4; 95% CI 2.4-8.1), and respiratory rate ≥ 20 breaths/min (OR 2.2; 95% CI 1.2-4.0)., Conclusion: We identified four clinical variables readily available to physicians upon patient arrival associated with meeting the critical administration threshold: systolic blood pressure ≤ 90 mmHg, Glasgow Coma Scale ≤ 8, heart rate ≥ 100 beats/minute, and respiratory rate ≥ 20 breaths/min. Patients presenting with any of these clinical parameters should prompt physicians to consider ordering blood products immediately., Competing Interests: Declarations Conflict of interest The authors declare that they have no financial disclosures or conflicts of interest., (© 2024. The Author(s), under exclusive licence to the Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited., Aim: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI., Methods: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI., Results: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke., Conclusion: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI., (© 2024 Wiley Periodicals LLC.)

An abnormal platelet count (PC) is common in acute venous thromboembolism (VTE) but its relationship with clinical outcomes remains ill-defined. We aimed to explore the association between baseline PC and the long-term risk of clinically relevant outcomes in a prospective cohort of 991 patients with acute VTE. We classified patients into four PC groups: very low (< 100 G/l), low (≥ 100 to < 150 G/l), normal (≥ 150 G/l to ≤ 450 G/l), and high (> 450 G/l). The primary outcome was major bleeding (MB), secondary outcomes were recurrent VTE and overall mortality. We examined the association between PC and clinical outcomes, adjusting for confounders, competing risk for mortality, and periods of anticoagulation. After a median follow-up of 30 months, 132 (13%) of patients experienced MB, 122 (12%) had recurrent VTE, and 206 (21%) died. Compared to patients with a normal PC, patients with a very low PC had a sub-distribution hazard ratio (SHR) for MB of 1.23 (95% confidence interval [CI] 0.52-2.91) and those with a high PC a SHR of 1.87 (95%CI 0.82-4.29). Patients with a low PC had a twofold increased VTE recurrence risk (SHR 2.05, 95%CI 1.28-3.28). Patients with low and very low PC had a hazard ratio for mortality of 1.43 (95%CI 0.99-2.08) and of 1.55 (95%CI 0.80-2.99), respectively. Our findings do not suggest a consistent relationship between baseline PC and long-term clinical outcomes in patients with VTE., (© 2024. The Author(s).)

Background: Whole blood (WB) resuscitation is increasingly used at trauma centers. Prior studies investigating outcomes in WB versus component-only (CO) resuscitation have been limited by small cohorts, low volumes of WB resuscitation, and unbalanced CO resuscitation. This study aimed to address these limitations using data from a high-volume Level I trauma center, which adopted a WB-first resuscitation paradigm in 2018. We hypothesized that the resuscitation method, WB or balanced CO, would have no impact on patient mortality., Methods: A single-center, retrospective cohort study of adults presenting as a trauma activation from July 2016 through July 2021 was performed. Receipt of three or more units of WB or packed red blood cells (RBC) within the first hour of resuscitation was required for inclusion. Patients were grouped into WB versus CO resuscitation and important clinical outcomes were compared. Mortality was evaluated with Kaplan-Meier analysis, log-rank testing, and multivariable Cox proportional hazards modeling., Results: There were 180 patients in the WB group and 170 patients in the CO group. Of the 180 WB patients, 110 (61%) received only WB during the first 24 hours. The WB group received a median of 5.0 units (interquartile range, 4.0-8.0) of WB and CO group received a median of 6.0 units (interquartile range, 4.0-11.8) of RBCs during the first 24 hours of resuscitation. In the CO group, median RBC/plasma and RBC/platelet ratios approximated 1:1:1. Groups were similar in clinicopathologic characteristics including age, Injury Severity Score, mechanism of injury, and requirement for hemorrhage control interventions (WB 55% vs. CO 59%, p = 0.60). Unadjusted survival was equivalent at 24 hours ( p = 0.52) and 30 days ( p = 0.70) between both groups on Kaplan-Meier analysis with log-rank testing. On multivariable Cox regression, WB resuscitation was not independently associated with improved survival after accounting for age, Injury Severity Score, mechanism of injury, and receipt of hemorrhage control procedure (hazard ratio, 0.85; 95% confidence interval, 0.61-1.19, p = 0.34)., Conclusion: Balanced CO resuscitation is associated with similar mortality outcomes to that of WB based resuscitation., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: 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., Methods: 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 used 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., Results: A total of 1,744 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 (interquartile range, 5-26). Tranexamic acid was independently associated with a lower risk of 28-day mortality (hazard ratio, 0.72; 95% confidence interval [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 (hazard ratio, 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 to -0.01; p = 0.04) with a dose-response relationship ( β= - 0.24; 95% CI, -0.45 to -0.02; p = 0.03). There was no independent association of prehospital TXA administration on thromboembolism, seizure, or stroke., Conclusion: 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 and lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Aim: To assess risk factors of retroperitoneal and lower extremity musculoskeletal bleed in acquired haemophilia (AHA) and perform an objective assessment of disability and influence on survival., Methods: We included 49 patients with AHA from November 2017 to May 2023. The occurrence of any retroperitoneal or/and lower extremities bleeding manifestation was investigated. On clinical follow-up, we search for compressive femoral neuropathy and quadriceps amyotrophy. The lower extremity functional scale (LEFS) was carried out one year after the last bleeding event in all AHA patients., Results: A 61.2% of patients in our AHA cohort presented with any retroperitoneal and/or lower extremities musculoskeletal manifestation. Those patients had higher percentage of major bleeding EACH2/ISTH criteria (90% vs. 57%, p = .01), needs of blood transfusions (86% vs. 57% of patients, p = .03), and haemostatic by-pass products (90% vs. 63%, p = .02). Hypertension (HR 2.6, 95% CI 1.1-5.9, p = .02), presence of autoimmune disease (HR 13, 95% CI 1.7-99, p = .01), and inhibitor level > 20 BU (HR 2.6 95% CI 1.0-6.8, p = .04) significantly predicted retroperitoneal/lower extremities clinical manifestations. Most frequent sequelae were quad atrophy (30.6%) and femoral nerve palsy (20.4%). Quad atrophy and LEFS scores under 50 were associated with increased mortality (HR 3, 95% CI 1.1-8.6 and HR 12, 95% CI 3.3-45, respectively)., Conclusion: AHA with retroperitoneal/lower extremities bleeding involvement is of greater severity and shows high disability and worst survival outcomes. Quadriceps atrophy and LEFS scale scoring under 50 predicted mortality in our AHA patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Patients with cirrhosis show alterations in primary hemostasis, yet prognostic implications of changes in platelet activation remain controversial, and assay validity is often limited by thrombocytopenia. We aimed to study the prognostic role of platelet activation in cirrhosis, focusing on bleeding/thromboembolic events, decompensation, and mortality., Approach and Results: We prospectively included 107 patients with cirrhosis undergoing a same-day hepatic venous pressure gradient (HVPG) and platelet activation measurement. Platelet activation was assessed using flow cytometry after protease-activated receptor (PAR)-1, PAR-4, or epinephrine stimulation. Over a follow-up of 25.3 (IQR: 15.7-31.2) months, first/further decompensation occurred in 29 patients and 17 died. More pronounced platelet activation was associated with an improved prognosis, even after adjusting for systemic inflammation, HVPG, and disease severity. Specifically, higher PAR-4-inducible platelet activation was independently linked to a lower decompensation risk [adjusted HR per 100 MFI (median fluorescence intensity): 0.95 (95% CI: 0.90-0.99); p =0.036] and higher PAR-1-inducible platelet activation was independently linked to longer survival [adjusted HR per 100 MFI: 0.93 (95% CI: 0.87-0.99); p =0.040]. Thromboembolic events occurred in eight patients (75% nontumoral portal vein thrombosis [PVT]). Higher epinephrine-inducible platelet activation was associated with an increased risk of thrombosis [HR per 10 MFI: 1.07 (95% CI: 1.02-1.12); p =0.007] and PVT [HR per 10 MFI: 1.08 (95% CI: 1.02-1.14); p =0.004]. In contrast, of the 11 major bleedings that occurred, 9 were portal hypertension related, and HVPG thus emerged as the primary risk factor., Conclusions: Preserved PAR-1- and PAR-4-inducible platelet activation was linked to a lower risk of decompensation and death. In contrast, higher epinephrine-inducible platelet activation was a risk factor for thromboembolism and PVT., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact., Methods: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. Prehospital blood patients were compared with trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mm Hg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest., Results: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs. 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs. 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19)., Conclusion: Compared with patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of prehospital tranexamic acid (TXA) in patients with trauma has attracted considerable attention. This systematic review and meta-analysis aimed to provide the best evidence for clinicians., Methods: All related literature in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (Central) databases were searched systematically from their establishment to July 1, 2023. The outcome measures included 24-hour and 28-30-day mortality and adverse events (multiple organ dysfunction syndrome, acute respiratory distress syndrome, thrombotic events, and infection events). The Revised Cochrane Risk of Bias Tool for Randomized Trials was used to evaluate the quality of the randomized controlled trials (RCTs). The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the risk of bias in non-RCTs. The required information size was estimated using trial sequential analysis. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to evaluate the evidence quality., Results: Eleven studies (comprising 11,259 patients) were included; two of these were RCTs. The overall risks of bias were low in the RCTs. ROBINS-I risk of bias was Moderate in 3 studies, serious in 5 studies, and critical in 1 study. A significant reduction in 24-hour mortality was observed (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71-0.94). A subgroup analysis that included only RCTs revealed that prehospital TXA was associated with reduced 28-30-day mortality (OR, 0.80; 95% CI, 0.66-0.97) and increased risks of thromboembolism (OR, 1.22; 95% CI, 1.03-1.44) and infection (OR, 1.13; 95% CI, 1.00-1.28) events. The blood products for transfusion decreased by 2.3 units on average (weighted mean difference [WMD], - 2.30; 95%CI, - 3.59 to - 1.01)., Conclusions: This updated systematic review showed that prehospital TXA reduced the 24-hour and 28-38-day mortality and blood transfusion but increased the risks of infection and thromboembolism in patients with trauma. Future RCTs with larger and more homogeneous samples will help verify our results., (© 2024. The Author(s).)

Background: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI., Methods: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied., Results: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23-7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08-1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50-2.87, p = 0.69)., Conclusions: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury., (© 2024. The Author(s).)

This case report of a 73-year-old male with bleedings provides insights into the clinical characteristics, diagnosis och treatment of acquired hemophilia A. It's a dangerous non-hereditary bleeding disorder caused by autoantibodies against coagulation factor VIII, often linked with other autoimmune diseases or malignancies, but it is also often idiopathic. The diagnosis remains a challenge due to its rarity and non-specific symtoms, but should be considered in unexplained bleeding cases with prolonged activated partial thromboplastin time (APTT). Quick  diagnosis and treatment can significantly reduce the risk of serious complications and mortality. The long-term prognosis usually depends on the presence of any underlying disease.

Background: Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials., Methods: Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding., Results: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort., Conclusions: In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs., (© 2024 BARMER Institut für Gesundheitssystemforschung and The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Evaluations of critical bleeding and massive transfusion have focused on traumatic hemorrhage. However, most critical bleeding in hospitalized patients occurs outside trauma. The purpose of this study was to provide an in-depth description examining the critical administration threshold (CAT; ≥3 units red blood cells (RBCs) in a 1-h period) occurrences in nontraumatic hemorrhage. This will assist in establishing the framework for future investigations in nontraumatic hemorrhage., Methods: This is an observational cohort study of adults experiencing critical bleeding defined as being CAT+ during hospitalization from 2016 to 2021 at a single academic institution. A CAT episode started with administration of the first qualifying RBC unit and ended at the time of completion of the last allogeneic unit prior to a ≥4-h gap without subsequent transfusion. The primary goal was to describe demographic, clinical and transfusion characteristics of participants with nontraumatic critical bleeding., Results: 2433 patients suffered critical bleeding, most often occurring in the operating room (71.1%) followed by the intensive care unit (20.8%). 57% occurred on the initial day of hospitalization, with a median duration of 138 (36, 303) minutes. The median number of RBCs transfused during the episode was 5 (4, 8), with median total allogeneic units of 9 (4, 9). Hospital mortality was 19.2%. The most common cause of death was multi-organ failure (50.3%), however death within 24 h was due to exsanguination (72.7%)., Discussion: The critical administration threshold may be employed to identify critical bleeding in non-trauma settings of life-threatening hemorrhage, with a mortality rate of approximately 20%., (© 2024 AABB.)

Introduction: Preperitoneal pelvic packing (PPP) has been advocated as a damage control procedure for pelvic fracture bleeding, despite of weak evidence., Methods: Matched cohort study, TQIP database. Patients with isolated severe blunt pelvic fractures (pelvis abbreviated injury score [AIS] ​≥ ​3, AIS ≤2 in all other body regions) were included. Patients who underwent PPP were matched to patients with no PPP, 1:3 nearest propensity score. Matching was performed based on demographics, vital signs on admission, comorbidities, injury characteristics, type and timing of initiation of VTE prophylaxis, and additional procedures including laparotomy, REBOA, and angioembolization., Results: 64 patients with PPP were matched with 182 patients with No-PPP. PPP patients had higher in-hospital mortality (14.1 ​% vs 2.2 ​% p ​< ​0.001) and higher rates of VTE and DVT (VTE: 14.1 ​% vs 4.4 ​% p ​= ​0.018, DVT: 10.9 ​% vs 2.2 ​% p ​= ​0.008)., Conclusion: PPP is associated with worse survival outcomes and increased rate of VTE and DVT complications., Competing Interests: Declaration of competing interest No conflicts of interests or disclosure by any of the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Haemorrhage is a leading cause of preventable mortality in high-income countries and emergency management presents unique challenges in the prehospital setting. The study aimed to determine incidence and characteristics of fatalities from prehospital haemorrhage in Sweden., Methods: A nationwide retrospective cohort study 2012-2021 was conducted using data from the Swedish National Board of Health and Welfare. Prehospital fatality from haemorrhage was defined as a cause of death related to haemorrhage (Appendix 1) without a hospital admission on the same day. Primary outcome was age-standardized mortality rate per 100,000 inhabitants., Results: A total of 9801 prehospital fatalities from haemorrhage were identified. Annual age-standardized mortality rate decreased from 10.97 to 8.18 per 100,000 population (coefficient =  - 0.28, r 2  = 0.85, p =  < 0.001). Trauma was the most common cause (3512, 35.83%) with intentional self-harm (X60-X84), transport accidents (V01-V99) and assault (X85-Y09) being the most common mechanisms of injury. Traumatic fatalities were younger and a larger proportion were male compared to non-traumatic causes (p < 0.001). Overall median Charlson Comorbidity Index (Quan) was 0 [0-2] with a lower index noted for traumatic causes (p < 0.001). Trauma resulted in a median of 26.1 [3.65-49.22] years of life lost per patient compared to 0 [0-3.65] for non-traumatic causes (p < 0.001). Regional variations in mortality rate were observed with lower population density correlating with higher mortality rate (ρ =  - 0.64, p = 0.002)., Conclusions: Prehospital mortality from haemorrhage decreased between 2012 and 2021. Trauma was the most common cause which resulted in many years of life lost in a population with a low burden of comorbidities. There were considerable regional differences with low population density associated with higher mortality rate from prehospital haemorrhage., (© 2024. The Author(s).)

Patients with immune thrombocytopenia (ITP) admitted for non-ST elevation myocardial infarction (NSTEMI) present a unique therapeutic challenge due to the increased risk of bleeding with antiplatelet and anticoagulation therapies. There is limited evidence studying hospital mortality and complications in this population. The study included a patient cohort from the 2018-2021 National Inpatient Sample database. Propensity score matched NSTEMI patients with and without ITP using a 1:1 matching ratio. Outcomes analyzed were in-hospital mortality, rates of diagnostic angiogram, percutaneous coronary intervention (PCI), acute kidney injury (AKI), congestive heart failure (CHF), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, ventricular tachycardia (VT), ventricular fibrillation (VF), major bleeding, need for blood and platelet transfusion, length of stay (LOS), and total hospitalization charges. A total of 1,699,020 patients met inclusion criteria (660,490 females [39%], predominantly Caucasian 1,198,415 (70.5%); mean [SD] age 67, [3.1], including 2,615 (0.1%) patients with ITP. Following the propensity matching, 1,020 NSTEMI patients with and without ITP were matched. ITP patients had higher rates of inpatient mortality (aOR 1.98, 95% CI 1.11-3.50, p 0.02), cardiogenic shock, AKI, mechanical ventilation, tracheal intubation, red blood cells and platelet transfusions, longer LOS, and higher total hospitalization charges. The rates of diagnostic angiogram, PCI, CHF, VT, VF, and major bleeding were not different between the two groups. Patients with ITP demonstrated higher odds of in-hospital mortality for NSTEMI and need for platelet transfusion with no difference in rates of diagnostic angiogram or PCI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study was conducted to identify the characteristics and risk factors for early death in critically ill acute promyelocytic leukaemia (APL) patients in the Hemato-oncology ICU (HICU). A total of 44 APL patients from 2017 to 2023 were included. The mortality among APL patients in the HICU was high (27/44, 61.36%). Compared with patients who survived, nonsurvivors had a longer prothrombin time (P = 0.002), lower fibrinogen (P = 0.022), higher white blood cell count (P = 0.004) and higher creatinine (P = 0.037) on hosipital admission. Severe bleeding was the most frequent complication (34 cases, 77.27%), which occurred either preinduction or on Day 5 (IQR 3-7.5 days) of induction. Cerebral bleeding associated with consciousness disturbance was the main reason for HICU admission (18 cases, 40.9%). The leading cause of death was fatal haemorrhage (18/34, 52.94%), which occurred either preinduction or on Day 4 (IQR 3-7 days) of induction. Another common cause of death was sepsis (8/18, 44.44%), which occurred on Day 12 (IQR 9.5-24.75 days) during induction. In conclusion, the main cause of death in APL patients treated in the HICU was primary being attributed to fatal bleeding, followed by sepsis., (© 2024. The Author(s).)

Background: There are few data assessing the risk of death and cardiovascular events in patients with lymphoma., Aim: Using a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma., Methods: From 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed., Results: After adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881-1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049-1.188) remained higher in patients with lymphoma., Conclusion: In this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored., Methods: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding., Results: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance., Conclusions: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Comparison of access times to CT and surgical/radiological bleeding control between two European military trauma centers., Methods: Retrospective and observational study conducted in two military level 1 trauma centers in Toulon (France) and Koblenz (Germany) between 2013 and 2018. Inclusion of severe trauma patients with ISS > 15 with clinical and biological criteria of bleeding., Results: Inclusion of 607 patients (318 in Toulon and 289 in Koblenz). Mean ISS 30. Median access time to CT significantly lower for Koblenz, 14 vs. 30 min; p < 0.001. Median access time to the emergency bleeding control lower in Toulon 84 min vs. 92 (p = 0.114). No impact on mortality at 24 h 9% in Koblenz and 11% in Toulon. Mortality at 28 days identical 17%., Conclusion: The organizational innovation at the military hospital in Koblenz saves time in the injury assessment. However, it has no impact on the access time to the scanner and on the mortality at 24 and 28 days. This fight against hemorrhage is a management bundle including delays, transfusion, and team training., Clinical Trial Registration: 2,002,878 v 0., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Evidence supports a restrictive platelet transfusion threshold in preterm neonates. We aimed to describe the effect of implementing this threshold on transfusion rates., Study Design and Methods: This retrospective observational cohort study included all very preterm infants (born <32 weeks' gestation) admitted to a neonatal intensive care unit between 2004 and 2022, divided into three epochs. Platelet transfusion thresholds changed from 30 × 10 9 /L for stable neonates and 50 × 10 9 /L for unstable neonates (January 2004 to December 2009) to 20 × 10 9 /L for stable neonates and 50 × 10 9 /L for unstable neonates (January 2010 to June 2019) to 25 × 10 9 /L for non-bleeding neonates and 50 × 10 9 /L for neonates with major bleeding (July 2019 to July 2022). The primary outcome was the percentage of transfused neonates in each epoch. Secondary outcomes included the median number of transfusions per neonate, the percentage of transfusions given above 25 or 50 × 10 9 /L, and major bleeding and mortality rates., Results: The percentage of neonates transfused was 12.2% (115/939), 5.8% (96/1660), and 4.8% (25/525) in Epoch I, II, and III, respectively (p < .001), a relative reduction of 61%. The median number of transfusions per transfused neonate was 2.0 (interquartile range [IQR]: 1.0-3.0) in Epoch I, and 1.0 (IQR: 1.0-2.0) in subsequent Epochs (p = .04). The percentage of infants receiving at least one transfusion above 50 × 10 9 /L in Epoch I, II, and III was 51.3% (59/115), 17.7% (17/96), and 20.0% (5/25; p < .001). Mortality and bleeding rates did not significantly differ between epochs., Discussion: Implementation of restrictive platelet guidelines led to reduction of the rate and number of platelet transfusions., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Objectives: To determine the effectiveness of an updated protocol that increased the transfusion threshold to perform preperitoneal pelvic packing in patients with pelvic ring injuries and hemodynamic instability (HDI)., Design: Retrospective review., Setting: Urban level 1 trauma center., Patients Selection Criteria: Severely injured (injury severity score > 15) patients with pelvic ring injuries treated before and after increasing the threshold to perform preperitoneal pelvic packing from 2 to 4 units of red blood cells (RBCs). HDI was defined as a systolic blood pressure <90 mm Hg., Outcome Measures and Comparisons: Mortality from hemorrhage, anterior pelvic space infections, and venous thromboembolisms before and after increasing preperitoneal pelvic packing threshold., Results: One hundred sixty-six patients were included: 93 treated under the historical protocol and 73 treated under the updated protocol. HDI was present in 46.2% (n = 43) of the historical protocol group and 49.3% (n = 36) of the updated protocol group (P = 0.69). The median age of patients with HDI was 35.0 years (interquartile range 26.0-52.0), 74.7% (n = 59) were men, and the median injury severity score was 41.0 (interquartile range 29.0-50.0). Patients with HDI in the updated protocol group had a lower heart rate on presentation (105.0 vs. 120.0; P = 0.004), required less units of RBCs over the first 24 hours (6.0 vs. 8.0, P = 0.03), and did not differ in age, injury severity score, systolic blood pressure on arrival, base deficit or lactate on arrival, resuscitative endovascular balloon occlusion of the aorta, resuscitative thoracotomy, angioembolization, or anterior pelvis open reduction internal fixation (P > 0.05). The number of PPPs performed decreased under the new protocol (8.3% vs. 65.1%, P < 0.0001), and there were fewer anterior pelvic infections (0.0% vs. 13.9%, P = 0.02), fewer VTEs (8.3% vs. 30.2%; P = 0.02), and no difference in deaths from acute hemorrhagic shock (5.6% vs. 7.0%, P = 1.00)., Conclusions: Increasing the transfusion threshold from 2 to 4 units of red blood cells to perform pelvic packing in severely injured patients with pelvic ring injuries decreased anterior pelvic space infections and venous thromboembolisms without affecting deaths from acute hemorrhage., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: None of the authors have financial conflicts of interest relevant to the content of this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Noncompressible truncal hemorrhage remains a leading cause of preventable death in the prehospital setting. Standardized and reproducible large animal models are essential to test new therapeutic strategies. However, existing injury models vary significantly in consistency and clinical accuracy. This study aims to develop a lethal porcine model to test hemostatic agents targeting noncompressible abdominal hemorrhages., Methods: We developed a two-hit injury model in Yorkshire swine, consisting of a grade IV liver injury combined with hemodilution. The hemodilution was induced by controlled exsanguination of 30% of the total blood volume and a 3:1 resuscitation with crystalloids. Subsequently, a grade IV liver injury was performed by sharp transection of both median lobes of the liver, resulting in major bleeding and severe hypotension. The abdominal incision was closed within 60 s from the injury. The endpoints included mortality, survival time, serum lab values, and blood loss within the abdomen., Results: This model was lethal in all animals (5/5), with a mean survival time of 24.4 ± 3.8 min. The standardized liver resection was uniform at 14.4 ± 2.1% of the total liver weight. Following the injury, the MAP dropped by 27 ± 8mmHg within the first 10 min. The use of a mixed injury model (i.e., open injury, closed hemorrhage) was instrumental in creating a standardized injury while allowing for a clinically significant hemorrhage., Conclusion: This novel highly lethal, consistent, and clinically relevant translational model can be used to test and develop life-saving interventions for massive noncompressible abdominal hemorrhage., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Most patients undergoing the mitral transcatheter edge-to-edge repair (TEER) technique are elderly comorbid patients. Low body mass index (BMI) < 23 kg/m 2 has been identified in other elderly populations as a risk factor, but has not been studied sufficiently in mitral TEER., Aims: We aimed to study the impact of low BMI (23 kg/m2) on the outcome after mitral TEER., Methods: Patients undergoing first-time TEER for mitral regurgitation at a single tertiary center were included, with the exclusion of patients with preprocedural hemodynamic instability or missing BMI. The primary endpoint was all-cause mortality. Secondary endpoints were long-term major bleeding or admission with heart failure., Results: A total of 120 patients (mean age 76 ± 10 years, 76% men) were included in the study. Thirty-nine (31%) had low BMI. Patients with low BMI had a similar symptomatic benefit as patients with BMI ≥ 23 kg/m 2 at 1 year regarding decrease in diuretics dose and decrease in New York Heart Association (NYHA) class (p > 0.05). In a multivariable Cox regression analysis, BMI as a continuous variable (hazard ratio [HR]: 0.93 [95% confidence interval, CI: 0.87-0.99], p = 0.03) and low BMI (HR: 1.99 [95% CI: 1.12-3.52], p = 0.02) were associated with the primary outcome. Low BMI was not significantly associated with major bleeding (subdistribution hazard ratio [SHR]: 2.39 [95% CI: 0.96-5.97], p = 0.06) or admission with heart failure (SHR: 1.06 [95% CI: 0.61-1.88], p = 0.83) during follow-up with univariable competing risk regression analysis., Conclusion: Low BMI is a risk factor for mortality after mitral valve TEER, confirming the presence of an "obesity paradox" in this population and should receive attention in patient selection., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk., Objectives: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT., Methods: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated., Results: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67)., Conclusions: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding., Trial Registration Number: NCT05150938 (Registered 9 December 2021)., (© 2024. The Author(s).)

Objective: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a resource-intensive approach for the management of refractory cardiogenic shock. Within this population exists a substantial cohort of patients with peripheral artery disease (PAD), which independently increases the risk of complications and all-cause mortality. We studied 10-year national trends of the impact of PAD among VA-ECMO recipients to better understand the prevalence of PAD and implications on outcomes in this vulnerable population., Methods: This 10-year retrospective, propensity score-matched study identified all adult patients (≥18) who underwent VA-ECMO between 2009 and 2018, from a large US database (National Inpatient Sample). Patients with an ICD diagnosis of PAD were identified. The primary endpoints of in-hospital mortality, bleeding complications and major limb loss (above- or below-knee amputation) were compared between patients with PAD to those without., Results: A total of 6768 patients were identified, of which 342 (5.3%) had PAD. The median age at admission was significantly higher in PAD patients [64 years vs. 55 years; p < .01], as was male gender [71% vs. 64%; p < .01]. Patients with PAD had higher rates of smoking (38.9% vs. 23.3%), hypertension (71.1% vs. 50%), diabetes (37.4% vs. 27.0%), chronic kidney disease (30.1% vs. 18.0%), coronary artery disease (76.0% vs. 35.0%) and dyslipidemia (76.0% vs. 35.0); all p < .01. After propensity-matching 2:1 for comorbidities, PAD patients were found to have significantly greater overall complications, including in-hospital mortality, bleeding, surgical wound infections, pseudoaneurysms, and major adverse limb events [71.9% vs. 63.9%; p < .01]. Subgroup analysis revealed greater in-hospital mortality [62.2% vs. 55.3%; p < .05], major amputations [4.1% vs. 0.3%; p < .01] and blood transfusions [32.2% vs. 26.2%; p < .05] in PAD patients. Over 2014-2018, the non-PAD group demonstrated statistically discernable trends in a 51.1% decrease in overall complications and a 28.1% increase in survival to discharge (all p < .01). Over the same time period the PAD cohort experienced a modest, nonsignificant, decrease in complications [7.0%, p = .40] and a decrease in those surviving to discharge [47.1% vs. 40.5%, p = .91]., Conclusion: Patients with PAD on VA-ECMO are sicker at baseline and experience significantly greater major amputations and higher in-hospital mortality. They have not benefitted from the considerable decrease in complication rates and increase in survival to discharge over time as compared to their non-PAD counterparts. These findings demonstrate the substantial frailty of the PAD population within an already high-risk cohort, and highlight the need for better procedural approaches and innovative technologies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Every year, thousands of people in Germany succumb to severe injuries. But what causes the death of these patients? In addition to the trauma, pre-traumatic health status, age, and other influencing factors play a role in the outcome after trauma. This study aims to answer the question of what causes the death of a severely injured patient.For this publication, in addition to previously published results, we examined current data from patients in German hospitals from the years 2015-2022 (8 years) documented in the TraumaRegister DGU®. The feature "Presumed Cause of Death", introduced in 2015, was considered. Patients transferred out early (< 48 h) as well as patients with minor injuries were excluded from this analysis.The number of fatalities decreases over time and does not correspond to a traditionally postulated tri-modal mortality distribution. Instead, over time, the distribution of causes of death shows significant variation. In over half of the cases (54%), traumatic brain injury (TBI) was the presumed cause of death, followed by organ failure (24%) and haemorrhage (9%). TBI dominates, especially in the first week, haemorrhage in the first 24 h, and organ failure as a cause steadily increases over time.In summary, it can be observed that the risk of death due to trauma-related consequences is highest in the first minutes, hours, and days, decreasing steadily over time. Particularly, the extent of injuries, head injuries, and significant blood loss are early risk factors., Competing Interests: RL gibt an, das seine Universität ein Service Agreement mit der Akademie der Unfallchirurgie (AUC GmbH) hat, dem Eigner des TR-DGU. DB gibt an, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)

Background: Besides its primary clinical utility in predicting bleeding risk in patients with acute coronary syndrome (ACS), the PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti-Platelet Therapy) score may also be useful for predicting long-term mortality in ACS patients presenting with cardiogenic shock (CS) since several studies have reported an association between the score and certain cardiovascular conditions or events. The aim of the present study was to evaluate the utility of the PRECISE-DAPT score for predicting the long-term all-cause mortality in patients (n = 293) with ACS presenting with CS., Methods: The PRECISE-DAPT score was calculated for each patient who survived in hospital, and the association with long-term mortality was studied. Median follow-up time was 2.7 years. The performance of the final model was determined with measurements of its discriminative power (Harrell's and Uno's C indices and time-dependent area under the receiver operating characteristic curve [AUC]) and predictive accuracy (coefficient of determination [R 2 ] and likelihood ratio χ 2 ). Hazard ratios (HRs) were used to assess the relationship between the variables of the model and long-term all-cause death., Results: All-cause death occurred in 197 patients (67%). There was a positive association between the PRECISE-DAPT score (change from 17 to 38 was associated with an HR of 2.42 [95% CI: 1.59-3.68], R 2  = 0.209, time-dependent AUC = 0.69) and the risk of death such that in the adjusted survival curve, the risk of mortality increased as the PRECISE-DAPT score increased., Conclusion: The PRECISE-DAPT score may be a useful easy-to-use tool for predicting long-term mortality in patients with ACS complicated by CS., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aims: Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF). However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population., Methods and Results: Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS programme studies were adjudicated by a central adjudication committee and classified following international guidance. Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11 040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia., Conclusion: The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF require further investigation, e.g. early rhythm control therapy and AF ablation., Trial Registration Numbers: NCT01606995, NCT01750788, NCT01800006., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients., Data Sources: A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood., Study Selection: All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included., Data Extraction: Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models., Data Synthesis: Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24-39) and 35.5 years (23-39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03-1.12]) and late (RR [95% CI] = 1.05 [1.01-1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias., Conclusions: These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings., Competing Interests: Dr. Spinella is a consultant for Cerus and Hemanext, on the advisory board for Haima and Octapharma, and is a Co-Founder and Chief Medical Officer of Kalocyte. He also has funding from Biomedical Advanced Research and Development Authority to perform a trial examining the safety and efficacy of whole blood. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Aims: Catheter-based therapies (CBTs) have been developed as a treatment option in patients with pulmonary embolism (PE). There remains a paucity of data to inform decision-making in patients with intermediate-risk or high-risk PE. The aim of this study was to characterize in-hospital and readmission outcomes in patients with intermediate-risk or high-risk PE treated with vs. without CBT in a large retrospective registry., Methods: Patients hospitalized with intermediate-risk or high-risk PE were identified using the 2017-20 National Readmission Database. In-hospital outcomes included death and bleeding and 30- and 90-day readmission outcomes including all-cause, venous thromboembolism (VTE)-related and bleeding-related readmissions. Inverse probability of treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT., Results: A total of 14 903 [2076 (13.9%) with CBT] and 42 829 [8824 (20.6%) with CBT] patients with high-risk and intermediate-risk PE were included, respectively. Prior to IPTW, patients with CBT were younger and less likely to have cancer and cardiac arrest, receive systemic thrombolysis, or be on mechanical ventilation. In the IPTW logistic regression model, CBT was associated with lower odds of in-hospital death in high-risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.80-0.87] and intermediate-risk PE (OR 0.76, 95% CI 0.70-0.83). Patients with high-risk PE treated with CBT were associated with lower risk of 90-day all-cause [hazard ratio (HR) 0.77, 95% CI 0.71-0.83] and VTE (HR 0.46, 95% CI 0.34-0.63) readmission. Patients with intermediate-risk PE treated with CBT were associated with lower risk of 90-day all-cause (HR 0.75, 95% CI 0.72-0.79) and VTE (HR 0.66, 95% CI 0.57-0.76) readmission., Conclusions: Among patients with high-risk or intermediate-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. Prospective, randomized trials are needed to confirm these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Aspirin, an effective, low-cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self-administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use., Methods and Results: We developed a population simulation model to determine the impact of self-administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643-14 574) deaths annually, after accounting for deaths due to bleeding (963; 926-1003). This translated to an estimated 166 309 YOLS (149391-185 505) at the cost of $643 235 (633 944-653 010) per year, leading to a cost-effectiveness ratio of $3.70 (3.32-4.12) per YOLS., Conclusions: For <$4 per YOLS, self-administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post-AMI outweighed the risk of bleeding deaths from aspirin 10 times over.

Purpose: Early administration and protocolization of massive hemorrhage protocols (MHP) has been associated with decreases in mortality, multiorgan system failure, and number of blood products used. Various prediction tools have been developed for the initiation of MHP, but no single tool has demonstrated strong prediction with early clinical data. We sought to develop a massive transfusion prediction model using machine learning and early clinical data., Methods: Using the National Trauma Data Bank from 2013 to 2018, we included severely injured trauma patients and extracted clinical features available from the pre-hospital and emergency department. We subsequently balanced our dataset and used the Boruta algorithm to determine feature selection. Massive transfusion was defined as five units at 4 h and ten units at 24 h. Six machine learning models were trained on the balanced dataset and tested on the original., Results: A total of 326,758 patients met our inclusion with 18,871 (5.8%) requiring massive transfusion. Emergency department models demonstrated strong performance characteristics with mean areas under the receiver-operating characteristic curve of 0.83. Extreme gradient boost modeling slightly outperformed and demonstrated adequate predictive performance with pre-hospital data only, as well as 4-h transfusion thresholds., Conclusions: We demonstrate the use of machine learning in developing an accurate prediction model for massive transfusion in trauma patients using early clinical data. This research demonstrates the potential utility of artificial intelligence as a clinical decision support tool., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial rapidly enrolled patients based on an Assessment of Blood Consumption (ABC) ≥ 2 score, or physician gestalt (PG) when ABC score was <2. The objective of this study was to describe what patients were enrolled by the two methods and whether patient outcomes differed based on these enrollments. We hypothesized that there would be no differences in outcomes based on whether patients were enrolled via ABC score or PG., Methods: Patients were enrolled with an ABC ≥ 2 or by PG when ABC was <2 by the attending trauma surgeon. We compared 1-hour, 3-hour, 6-hour, 12-hour, 18-hour, and 24-hour mortality, 30-day mortality, time to hemostasis, emergent surgical or interventional radiology procedure and the proportion of patients who required either >10 units of blood in 24 hours or >3 units in 1 hour., Results: Of 680 patients, 438 (64%) were enrolled on the basis of an ABC score ≥2 and 242 (36% by PG when the ABC score was <2). Patients enrolled by PG were older (median, 44; interquartile range [IQR], 28-59; p < 0.001), more likely to be White (70.3% vs. 60.3%, p = 0.014), and more likely to have been injured by blunt mechanisms (77.3% vs. 37.2%, p < 0.001). They were also less hypotensive and less tachycardic than patients enrolled by ABC score (both p < 0.001). The groups had similar Injury Severity Scores in the ABC ≥ 2 and PG groups (26 and 27, respectively) and were equally represented (49.1% and 50.8%, respectively) in the 1:1:1 treatment arm. There were no significant differences between the ABC score and PG groups for mortality at any point. Time to hemostasis (108 for patients enrolled on basis of Gestalt, vs. 100 minutes for patients enrolled on basis of ABC score), and the proportion of patients requiring a massive transfusion (>10 units/24 hours) (44.2% vs. 47.3%), or meeting the critical administration threshold (>3 unit/1 hour) (84.7% vs. 89.5%) were similar ( p = 0.071)., Conclusion: Early identification of trauma patients likely to require a massive transfusion is important for clinical care, resource use, and selection of patients for clinical trials. Patients enrolled in the PROPPR trial based on PG when the ABC score was <2 represented 36% of the patients and had identical outcomes to those enrolled on the basis of an ABC score of ≥2., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 American Association for the Surgery of Trauma.)

Introduction: Hemorrhagic cystitis (HC) is a devastating complication of bone marrow (BMT) and stem cell transplant (SCT). Much of the literature has focused on exclusively adult patient populations, with limited evidence regarding risk factors for mortality and morbidity among pediatric HC patients., Objective: To examine factors associated with all-cause mortality in children with HC after BMT/SCT., Methods: The Pediatric Health Information System database was queried for patients with ICD-9/10 codes for hematopoietic transplant and gross hematuria, hematuria unspecified, or cystitis with hematuria. Multivariable logistic regression examined association of medical and surgical interventions frequently employed for hemorrhagic cystitis with mortality and genitourinary morbidity, defined as having received instillation of any bladder medication or having undergone any genitourinary procedure., Results: A total of 811 patients, mean age of 12.4 years and 62% male, were included. Primary diagnosis included 388 (49%) leukemia/lymphoma, 182 (22%) blood dyscrasia, 99 (12%) solid organ tumor, 27 (3%) metabolic disease, 115 (14%) unknown. Transplant type included 377 (46%) bone marrow, 329 (41%) stem cell, 105, and (13%) unknown. Performing any bladder instillation (p < 0.0001) or any type of GU procedure (p < 0.0001) was significantly associated with mortality. On multivariate analysis, dialysis (OR = 10.7, 95% CI = 5.7-20.2), genitourinary morbidity (OR = 4, 95% CI = 2.2-6.8) and intravenous cidofovir (OR = 2.0, 95% CI = 1.2-3.3) were significantly associated with all cause mortality. Having an underlying diagnosis of blood dyscrasia was protective against mortality (OR = 0.425, CI = 0.205-0.88)., Discussion: In this large retrospective study evaluating factors associated with mortality in children with HC, all cause mortality was found to be 11%. This is probably an underrepresentation of true mortality in this population, as many patients discharged from the hospital likely die outside the hospital at home or hospice care. This study supports the current literature that invasive GU procedures are not associated with increased survival in patients with severe HC. This study is limited by retrospective use of a billing database that has the potential for errors in data entry and missing data. Patients who were discharged from the hospital were not captured by the PHIS which only collects data from inpatient stays., Conclusions: Patients with HC who received dialysis, intravenous cidofovir, or underwent GU intervention had significantly higher all-cause mortality. High grade HC is a marker of disease severity and efforts should be made by urologists and oncologists to maximize quality of life and limit futile treatments in this patient population., Competing Interests: Conflicts of interest None., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown., Methods: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI)., Results: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09-1.71), thrombotic events (HR 1.37, 95%CI 1.32-1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33-1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE., Conclusion: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis., (© 2024. The Author(s).)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed., Methods: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score., Results: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival., Conclusions: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care., (© 2024. The Author(s).)

Background: Evaluation of the residual risk in patient with chronic coronary syndrome is challenging in daily practice. Several types of events (myocardial infarction, ischemic stroke, bleeding, and heart failure [HF]) may occur, and their impact on subsequent mortality is unclear in the era of modern evidence-based pharmacotherapy., Methods: CORONOR (Suivi d'une cohorte de patients Coronariens stables en région Nord-pas-de-Calais) is a prospective multicenter cohort that enrolled 4184 consecutive unselected outpatients with chronic coronary syndrome. We analyzed the incidence, correlates, and impact of ischemic events (a composite of myocardial infarction and ischemic stroke), major bleeding (Bleeding Academic Research Consortium 3 or higher), and hospitalization for HF on subsequent patient mortality., Results: During follow-up (median, 4.9 years), 677 patients (16.5%) died. The 5-year cumulative incidences (death as competing event) of ischemic events, major bleeding, and HF hospitalization were 6.3% (5.6%-7.1%), 3.1% (2.5%-3.6%), and 8.1% (7.3%-9%), respectively. Ischemic events, major bleeding, and HF hospitalization were each associated with all-cause mortality. Major bleeding and hospitalization for HF were associated with the highest mortality rates in the postevent period (42.4%/y and 34.7%/y, respectively) compared with incident ischemic events (13.1%/y). The age- and sex-adjusted hazard ratios for all-cause mortality were 3.57 (95% CI, 2.77-4.61), 9.88 (95% CI, 7.55-12.93), and 8.60 (95% CI, 7.15-10.35) for ischemic events, major bleeding, and hospitalization for HF, respectively (all P <0.001)., Conclusions: Hospitalization for HF has become both the most frequent and one of the most ominous events among patients with chronic coronary syndrome. Although less frequent, major bleeding is strongly associated with worse patient survival. Secondary prevention should not be limited to preventing ischemic events. Minimizing bleeding and preventing HF may be at least as important., Competing Interests: Disclosures None.

Background: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality., Methods and Results: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P <0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03])., Conclusions: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Thromboembolic events and bleeding are known complications in essential thrombocythaemia (ET) and polycythaemia vera (PV). Using multiple Swedish health care registers, we assessed the rate of arterial and venous events, major bleeding, all-cause stroke and all-cause mortality in ET and PV compared to matched controls. For each patient with ET (n = 3141) and PV (n = 2604), five matched controls were randomly selected. In total, 327 and 405 arterial or venous events were seen in the group of ET and PV patients respectively. Compared to corresponding controls, the rate of venous thromboembolism, major bleeding and all-cause mortality per 100 treatment years was significantly increased among both ET (0.63, 0.79 and 3.70) and PV patients (0.94, 1.20 and 4.80). The PV patients also displayed a significantly higher rate of arterial events and all-cause stroke compared to controls. When dividing the cohort into age groups, we found a significantly higher rate of arterial and venous events in all age groups of PV patients, and the rate of all-cause mortality was significantly higher in both ET and PV patients in all ages above the age of 50. This study confirms that PV and ET are diseases truly marked by thromboembolic complications and bleeding., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation., Methods: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding., Results: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04., Conclusion: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Whole blood (WB) transfusion has been shown to improve mortality in trauma resuscitation. The optimal ratio of packed red blood cells (pRBC) to WB in emergent transfusion has not been determined. We hypothesized that a low pRBC/WB transfusion ratio is associated with improved survival in trauma patients., Methods: We analyzed the 2021 Trauma Quality Improvement Program (TQIP) database to identify patients who underwent emergent surgery for hemorrhage control and were transfused within 4 hours of hospital arrival, excluding transfers or deaths in the emergency department. We stratified patients based on pRBC/WB ratios. The primary outcome was mortality at 24 hours. Logistic regression was performed to estimate odds of mortality among ratio groups compared with WB alone, adjusting for injury severity, time to intervention, and demographics., Results: Our cohort included 17,562 patients; of those, 13,678 patients had only pRBC transfused and were excluded. Fresh frozen plasma/pRBC ratio was balanced in all groups. Among those who received WB (n = 3,884), there was a significant increase in 24-hour mortality with higher pRBC/WB ratios (WB alone 5.2%, 1:1 10.9%, 2:1 11.8%, 3:1 14.9%, 4:1 20.9%, 5:1 34.1%, p = 0.0001). Using empirical cutpoint estimation, we identified a 3:1 ratio or less as an optimal cutoff point. Adjusted odds ratios of 24-hour mortality for 4:1 and 5:1 groups were 2.85 (95% confidence interval [CI], 1.19-6.81) and 2.89 (95% CI, 1.29-6.49), respectively. Adjusted hazard ratios of 24-hour mortality were 2.83 (95% CI, 1.18-6.77) for 3:1 ratio, 3.67 (95% CI, 1.57-8.57) for 4:1 ratio, and 1.97 (95% CI, 0.91-4.23) for 5:1 ratio., Conclusion: Our analysis shows that higher pRBC/WB ratios at 4 hours diminished survival benefits of WB in trauma resuscitation. Further efforts should emphasize this relationship to optimize trauma resuscitation protocols., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies., Study Design and Methods: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses., Results: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex., Conclusion: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age., (© 2024 AABB.)

Introduction: Military experience has demonstrated mortality improvement when advanced resuscitative care (ARC) is provided for trauma patients with severe hemorrhage. The benefits of ARC for trauma in civilian emergency medical services (EMS) systems with short transport intervals are still unknown. We hypothesized that ARC implementation in an urban EMS system would reduce in-hospital mortality., Methods: This was a prospective analysis of ARC bundle administration between 2021 and 2023 in an urban EMS system with 70,000 annual responses. The ARC bundle consisted of calcium, tranexamic acid, and packed red blood cells via a rapid infuser. Advanced resuscitative care patients were compared with trauma registry controls from 2016 to 2019. Included were patients with a penetrating injury and systolic blood pressure ≤90 mm Hg. Excluded were isolated head trauma or prehospital cardiac arrest. In-hospital mortality was the primary outcome of interest., Results: A total of 210 patients (ARC, 61; controls, 149) met the criteria. The median age was 32 years, with no difference in demographics, initial systolic blood pressure or heart rate recorded by EMS, or New Injury Severity Score between groups. At hospital arrival, ARC patients had lower median heart rate and shock index than controls ( p ≤ 0.03). Fewer patients in the ARC group required prehospital advanced airway placement ( p < 0.001). Twenty-four-hour and total in-hospital mortality were lower in the ARC group ( p ≤ 0.04). Multivariable regression revealed an independent reduction in in-hospital mortality with ARC (odds ratio, 0.19; 95% confidence interval, 0.05-0.68; p = 0.01)., Conclusion: Early ARC in a fast-paced urban EMS system is achievable and may improve physiologic derangements while decreasing patient mortality. Advanced resuscitative care closer to the point of injury warrants consideration., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 American Association for the Surgery of Trauma.)

Background: During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to pulmonary embolism (PE)., Methods: We performed a systematic review and meta-analysis of the existing literature that focused on the use of thrombolytics for cardiac arrest due to presumed or confirmed PE. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge, neurologically-intact survival, and bleeding complications., Results: Thirteen studies with a total of 803 patients were included in this review. Most studies included were single-armed and retrospective. Thrombolytic agent and dose were heterogeneous between studies. Among those with control groups, intravenous thrombolysis was associated with higher rates of ROSC (OR 2.55, 95% CI = 1.50-4.34), but without a significant difference in survival to hospital discharge (OR 1.41, 95% CI = 0.79-2.41) or bleeding complications (OR 2.21, 0.95-5.17)., Conclusions: Use of intravenous thrombolytics in cardiac arrest due to confirmed or presumed PE is associated with increased ROSC but not survival to hospital discharge or change in bleeding complications. Larger randomized studies are needed. Currently, we recommend continuing to follow existing consensus guidelines which support use of thrombolytics for this indication.