Bleeding-related Mortality Research Articles

Predicting intracranial bleeding during anticoagulation for venous thromboembolism within different time frames: Findings from the RIETE registry

BackgroundThe risk of intracranial bleeding during anticoagulation for venous thromboembolism (VTE) is substantial and persists beyond the initial treatment phase. We aimed to refine risk-assessment through phase-specific prognostic scores. MethodsWe identified data from 77,786 VTE patients in the RIETE registry from March 2009 to October 2023 to develop two prognostic scores for intracranial bleeding. Multivariable Cox regression was used to analyze distinct variables for the early (≤90 days) and late (>90 days) phases, with comparative validation against existing scores (modified ACCP, RIETE, VTE-BLEED, and CHAP). ResultsIntracranial bleeding occurred in 411 patients (0.53 %), with 208 cases in the early phase and 203 in the late phase. The 30-day mortality was 45 % and 35 %, respectively. Shared significant predictors for both phases include baseline abnormal mental status, brain cancer, recent intracranial bleeding, and epilepsy. Unique to early-phase bleeding were body weight, non-brain cancer, hypertension, dementia, thrombocytopenia, renal insufficiency, and thrombolytic therapy. Advanced age, pulmonary embolism initially, prior stroke, depression, treatment with direct oral anticoagulants, and use of corticosteroids predicted late-phase bleeding. Both prognostic scores showed a c-statistic of 0.68, outperforming existing scores. ConclusionsThe study introduces two temporal prognostic scores for intracranial bleeding during anticoagulation for VTE. By discerning specific risk factors pertinent to each treatment phase, these scores outperform traditional models, offering an advanced tool for clinical decision-making. They hold significant potential for optimizing anticoagulation management and reducing bleeding-related mortality.

Geo-demographic trends in nontraumatic subarachnoid hemorrhage-related mortality among older adults in the United States, 1999-2020.

Nontraumatic subarachnoid hemorrhage (ntSAH) often results from a ruptured aneurysm and correlates with significant morbidity and mortality, particularly among the older population. Despite its impact, limited comprehensive studies evaluate the longitudinal trends in ntSAH-related mortality in older adults in the United States (US). The authors conducted a retrospective analysis using the CDC WONDER database from 1999 to 2020, analyzing Multiple Cause-of-Death Public Use death certificates to identify ntSAH as a contributing factor in the death of adults aged 65 years and older. We calculated age-adjusted mortality rates (AAMR) and annual percent change (APC) to examine trends across demographic variables such as sex, race/ethnicity, urbanization, and states/census region. A total of 78,260 ntSAH-related deaths (AAMR 8.50 per 100,000 individuals) occurred among older adults in the US from 1999 to 2020. The overall AAMR for ntSAH decreased from 9.98 in 1999 to 8.67 in 2020 with an APC of -0.7% [95% CI (-1.0, -0.3)]. However, the authors observed a noticeable rise from 2013 to 2020 with an APC of 1.7% [95% CI (0.8, 2.6)]. Sex, racial, and regional disparities were evident with higher mortality rates for ages 85 or greater (crude mortality rate 16.6), women (AAMR 9.55), non-Hispanic Asian or Pacific Islander (AAMR 12.5), and micropolitan areas (AAMR 8.99), and Western US (AAMR 8.65). Mortality from ntSAH increases with age, affects women disproportionately, and occurs more often in an inpatient setting. These findings necessitate targeted, multi-dimensional health policies and clinical interventions. Specialties beyond neurosurgery can utilize this data for improved risk stratification and early treatment. Policymakers should focus on equitable resource allocation and community-level interventions to mitigate these trends effectively.

Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis.

The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. The analysis included 12011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%]. Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Anastomotic bleeding from invaginated pancreaticogastrostomy following pancreatoduodenectomy: incidence, risk factors, treatment and prevention.

Meta-analysis of 10 randomized prospective trials demonstrated a higher risk of postoperative bleeding from pancreaticogastrostomy (PG) compared with pancreatojejunostomy following pancreatoduodenectomy (PD). This study evaluated the incidence, risk factors, and treatment of anastomotic bleeding from invaginated PG. We retrospectively evaluated all consecutive PDs performed between April 1, 2011 and December 31, 2022 using invaginated PG by the double purse-string technique. Multivariate analysis identified risk factors for anastomotic PG bleeding. During the study, 695 consecutive patients with a median age of 66 years underwent PD; the majority was performed for ductal pancreatic adenocarcinomas. Simultaneous vascular resections were performed in 328 patients. Postoperative mortality was 4.1%. Bleeding from PG occurred in 33(4.6%) patients at a median interval of 5 days (range, 1-14) from surgery, leading to reoperation in 21(63%). PG bleeding-related mortality was 9.0%. Multivariate analyses identified a soft pancreatic texture and Wirsung duct > 3 or ≤ 3mm (Class C and D, respectively, of the ISGPS) (odds ratio [OR]: 2.17, 95% confidence interval [95% CI]: 1.38-3.44; P = 0.0009) and wrapping of the invaginated pancreas (OR: 0.37, 95% CI: 0.17-0.84; P = 0.01) as independent risk factors for PG bleeding. In a large volume setting, anastomotic bleeding from invaginated PG occurred in ~ 5% of patients and was associated with soft pancreatic parenchyma and small wirsung duct. The reduced rate of PG bleeding observed with wrapping of the invaginated pancreatic stump warrants further evaluation in a prospective randomized study.

СОВЕРШЕНСТВОВАНИЕ ТАКТИКИ ЛЕЧЕНИЯ БОЛЬНЫХ С ГАСТРОДУОДЕНАЛЬНЫМИ ЯЗВЕННЫМИ КРОВОТЕЧЕНИЯМИ

Relevance. The purpose of the study is to evaluate the clinical results of treatment of patients with gastroduodenal bleeding with active endoscopic tactics. Material and methods. We analyzed the results of treatment of 191 patients with gastroduodenal bleeding of non-variceal etiology who were treated at the State Budgetary Institution of the Republic of Dagestan Republican Clinical Hospital of Emergency Medical Care (Makhachkala) from 2017 to 2023. The age of the patients ranged from 26 to 78 years, men – 98 (51.3%) and women – 93 (48.7%). In case of acute gastroduodenal bleeding, there was a history of use of alcoholic beverages in 75 (18.3%) of the studied patients, and non-steroidal anti-inflammatory drugs in 42 (22%). Upon admission and endoscopy, patients were divided into two groups with a high and low risk of gastroduodenal bleeding. Patients at low risk of bleeding were <60 years of age; without low hemodynamic disturbances and hemoglobin not lower than 70 g/l. Results. The high-risk group included 56 (29.3%) patients, and the low-risk group included 135 (70.7%) patients. Both groups were dominated by men. Comorbidities (p<0.01) and nonsteroidal anti-inflammatory drug (NSAID) use (p<0.01) were more frequent in the high-risk group. Gastric ulcer was the cause of bleeding in 90 (47.1%) compared with duodenal ulcer observed in 101 (52.9%). However, bleeding-related mortality in the very elderly group was greater than 8% (14.3%) vs 6% (4.4%; p=0.02). In multivariate analysis, only shock on admission was independently associated with mortality (p =0.02).With the active implementation of a multidisciplinary approach in the surgical department, out of 191 patients with profuse bleeding Forrest IA, IIB, 8 (4.2%) patients were operated on, including 4 with recurrent bleeding. Mortality after surgical treatment from 8 operated on in 2 (25%) patients. After endovascular hemostasis, out of 19 patients, mortality was found in 1 (5.3%) patients, and after combined hemostasis out of 164 – in 5 (3%) people. Conclusion. A multidisciplinary approach to the treatment of acute gastroduodenal bleeding gives positive results. The use of prophylactic and therapeutic transarterial embolization is feasible in patients with OGDC, when the risk after endoscopic hemostasis is high. For recurrent bleeding, endovascular hemostasis should be the preferred method in elderly comorbid patients for whom surgery is an undesirable treatment option.

Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial

PurposeTo determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. Materials and MethodsThis was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician’s discretion. The primary outcome was periprocedural platelet transfusion in each arm. ResultsEighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26–43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9–31.7) compared with SOC group (100%; 95% CI, 88.1–100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9–31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2–27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1–17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. ConclusionsTEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Benefit and Harm of Aspirin on Mortality From Gastrointestinal Cancers Vs Bleeding in Helicobacter pylori–Eradicated Patients

We investigated the benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer vs excess mortality from bleeding among Helicobacter pylori-eradicated patients, and its interaction with proton pump inhibitors (PPIs). H pylori-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from the date of H pylori therapy until death or the end of the study (July 2020). Primary exposure was aspirin use as time-varying variable. The primary outcome was GI cancer-related (gastrointestinal, hepatobiliary, or pancreatic cancer) death and the secondary outcome was bleeding-related (gastrointestinal bleeding or intracranial bleeding) death. The adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities, and concomitant medications. The benefit-risk profile was expressed as the adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and nonusers. A total of 87,967 subjects were followed up for a median of 10.1 years, with 1294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR, 0.51; 95% CI, 0.42-0.61), but higher bleeding-related mortality (aHR, 1.52; 95% CI, 1.11-2.08). Among PPI users, the aHR of bleeding-related mortality with aspirin was 1.06 (95% CI, 0.70-1.63). For the whole cohort, the adjusted absolute risk difference between aspirin users and nonusers was 7 (95% CI, 5-8) fewer cancer-related and 1 (95% CI, 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95% CI, 8-10) fewer cancer-related deaths per 10,000 person-years without an increase in bleeding-related deaths. GI cancer mortality benefit from aspirin outweighs bleeding-related mortality in H pylori-eradicated subjects, which is enhanced further by PPI use.

Should soldiers take oral tranexamic acid before going into battle?

Tranexamic acid is an inexpensive antifibrinolytic treatment that reduces morbidity and mortality in civilian and military trauma patients. It must be administered within 3 hours of the injury, and its efficacy is greater the earlier it is given. It is already used preventively in the civilian environment in a number of indications to reduce bleeding and bleeding-related mortality. We wondered about the potential benefits of preventive oral administration of tranexamic acid prior to an assault for military personnel with a potential risk of injury.

Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial

High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3-and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference,-3.3; 95% confidence interval,-11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P<.001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

A ten-year comparison of treatment and outcomes of cancer-associated thrombosis to non-cancer venous thromboembolism: from traditional anticoagulants to direct oral anticoagulants.

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.

Early double-balloon enteroscopy was not related to better clinical outcomes in patients with suspected overt small bowel bleeding.

Device-assisted enteroscopy has been used for over 20 years for the management of patients with suspected small bowel bleeding. Unlike esophagogastroduodenoscopy and colonoscopy, the appropriate timing of enteroscopy is still unknown. In recent guidelines, early enteroscopy is suggested to maximize diagnostic yield and therapeutic yield in patients with suspected small bowel bleeding. However, few studies have identified its influence on clinical outcomes, including mortality or rebleeding rate. We conducted this study to evaluate the influence of the timing of double-balloon enteroscopy on clinical outcomes in patients with suspected small bowel bleeding. Patients with overt small bowel bleeding who underwent double-balloon enteroscopy from January 2013 to February 2021 were retrospectively reviewed. Patients were categorized into an early enteroscopy group (≤14 days) and a nonearly enteroscopy group (>14 days). Clinical outcomes, including short-term mortality and rebleeding rate, long-term mortality and rebleeding rate, diagnostic yield, and therapeutic yield, were analyzed. A total of 100 patients (mean age, 66.2 years; 53% male) were included, and 44 patients were stratified into the early enteroscopy group. The diagnostic yield, therapeutic yield, mortality, and rebleeding rate were similar between two groups. In multivariate conditional logistic regression analysis, there were no significant differences between two groups regarding the 30-day rebleeding rate (adjusted odds ratio [aOR], 1.43; 95% CI, 0.47-4.33), 90-day rebleeding rate (aOR, 1.18; 95% CI, 0.47-2.94), 30-day mortality rate (aOR, 1.29; 95% CI, 0.21-8.13), 90-day mortality rate (aOR, 1.94; 95% CI, 0.48-7.87), and 90-day bleeding-related mortality (aOR, 2.18; 95% CI, 0.24-19.52). The Kaplan-Meier survival curve analysis showed that the timing of DBE was not associated with the long-term rebleeding rate or mortality rate ( p = 0.57 and 0.83, respectively). The timing of enteroscopy did not influence the clinical outcomes, including the short-term mortality rate, short-term rebleeding rate, long-term mortality rate, and rebleeding rate, in patients with suspected overt small bowel bleeding.

Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis

BackgroundCritical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations.MethodsLiterature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability.DiscussionEvidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting.Systematic review registrationCRD42020161206.

Statins, metformin, and RAS inhibitors did not reduce variceal bleeding risk and mortality in a large, real-life cohort of patients with cirrhosis.

Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated. Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications. A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118). In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.

Post-Immune Tolerance Induction Prophylactic FVIII Infusions May Not be Necessary for Tolerized Hemophilia a Patients on Emicizumab

Background: Hemophilia A is a hereditary bleeding disorder characterized by low factor VIII (FVIII) activity. Patients with severe bleeding phenotypes are at risk for significant bleeding-related morbidity and mortality including the development of hemophilic arthropathy. In recent years, prophylaxis with emicizumab, a bispecific monoclonal antibody, has supplanted prophylactic FVIII infusions due to its ease of self-administration, long half-life, and low annual bleeding rate (ABR), independent of tolerization status to alloantibodies against FVIII (inhibitors). However, it is unclear if emicizumab FVIII-mimic activity is sufficient to achieve hemostasis in moderate-severe bleeds, and therefore, FVIII replacement may still be necessary. Despite its well-established benefits, the use of emicizumab in previously untreated patients (PUPs), and patients with under 20 exposures to FVIII is still not well understood due to a lack of long-term experience and understanding of its impact on the pathophysiology of FVIII inhibitors. Further investigation is also needed regarding the risk of inhibitor recurrence in patients with previous inhibitors and the concomitant use of emicizumab. At our institution, patients on emicizumab with a history of inhibitors do not continue post-immune tolerance induction prophylactic FVIII infusions. We also initiate emicizumab before 20 exposures to FVIII, and sometimes before immune tolerance induction (ITI). We explored our patient population to understand inhibitor incidence and recurrence amidst emicizumab prophylaxis. Methods: We performed a single center retrospective analysis of patients served by the Hemophilia Center of Western Pennsylvania. We identified patients with Hemophilia A on emicizumab prophylaxis. Relevant data was collected including demographics, inhibitor status at time of transition to emicizumab and in the available follow-up period, bleeding events after transition, and number of FVIII exposures before and after transition. Inhibitor recurrence was defined as laboratory evidence of inhibitor using chromogenic Bethesda assay and/or unexplained breakthrough bleeding events despite on-demand FVIII infusions. Results: Data was reviewed for 36 patients on emicizumab prophylaxis. Three patients were lost to follow-up. Median age was 15.3 years (range 1.2 - 82). Median follow-up time on emicizumab was 3.5 years (range 0.5 - 5). Two patients had &amp;lt; 20 FVIII exposures prior to emicizumab, and one of those had an inhibitor before emicizumab. In total, 15 patients (45%) were diagnosed with an inhibitor prior to emicizumab. Of these, 8 patients (53%) were tolerized prior to emicizumab, and 7 patients (47%) were not tolerized prior to emicizumab. Median peak inhibitor titer was 4.2 Bethesda units (range 0.7 - 281 Bethesda units). After transition to emicizumab, no tolerized patients for which inhibitor status was tested during the follow-up period had inhibitor recurrence, and 1 non-tolerized patient's inhibitor became undetectable after 4 years of emicizumab therapy (the same patient who had developed an inhibitor with &amp;lt; 20 FVIII exposures prior to emicizumab). Mean ABR was 0.33 events/year for tolerized patients (median 0, range 0 - 3); 0.17 events/year for non-tolerized patients (median 0, range 0 - 1); and 0.60 events/year for patients with no history of inhibitor (median 0, range 0 - 4). Mean number of FVIII exposures per year was 0.09 for tolerized patients (median 0, range 0 - 1); 0.07 for non-tolerized patients (median 0, range 0 - 1); and 1.2 for patients with no history of inhibitor (median 0, range 0 - 20). Conclusion: In our small cohort, no patient who was tolerized prior to emicizumab had recurrence of clinical or laboratory evidence of inhibitor while on emicizumab therapy, despite infrequent exposure to FVIII infusion. We did not have enough power to determine whether patients with &amp;lt; 20 FVIII exposures before emicizumab developed inhibitors, though one such patient had inhibitor resolution on emicizumab without ITI. Consistent with other works, overall ABRs in all patients on emicizumab therapy were low. These findings add to other studies on the safety of emicizumab and its impact on the natural history of FVIII inhibitors. Our study also suggests that continuing post-ITI prophylactic FVIII infusions in tolerized patients on emicizumab may not be necessary. Larger-scale studies are required to substantiate our findings.

Predicting the risk of early bleeding following endoscopic variceal ligation in cirrhotic patients with computed tomography

BackgroundLife-threatening bleeding following endoscopic variceal ligation (EVL) in patients with cirrhosis rarely can occur. The present study aimed to evaluate the performance of computed tomography (CT) in predicting the risk of early bleeding following EVL in cirrhotic patients.MethodsWe retrospectively investigated 285 cirrhotic patients who had undergone EVL. EVL was performed for prophylaxis or acute variceal bleeding. The patients were classified into 2 groups: early bleeding (< 14 days after EVL) and non-early bleeding. We compared baseline characteristics including CT findings between the patient groups.ResultsAmong the 285 patients who underwent EVL treatment, 19 patients (6.7%) experienced early bleeding. On average, these bleeding occurred 9.3 ± 3.5 days after the EVL, with a range of 3 to 13 days. Patients who experience early bleeding had a higher six-week bleeding-related mortality rate compared to those in the non-early bleeding group (31.6% vs. 10.2%; p = 0.014). There was a correlation between the grade of esophageal varix observed during endoscopy and the diameter of esophageal varix observed on CT (p < 0.001). The diameter of esophageal varix on CT was identified as the only significant predictive factor for early bleeding (p = 0.005).ConclusionA larger esophageal varix diameter observed on CT is associated with an increased risk of early bleeding after EVL treatment. Early identification of this high-risk group can provide a change of treatment strategies to improve patient outcomes.

Balanced resuscitation and earlier mortality end points: bayesian post hoc analysis of the PROPPR trial

IntroductionThe Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial failed to demonstrate a mortality difference for hemorrhaging patients receiving a balanced (1:1:1) vs a 1:1:2 resuscitation at 24 hours...

Evaluation of the association of factor XIII at hospital arrival and outcomes in a cohort of severely injured patients

BackgroundSevere traumatic bleeding depletes coagulation factor XIII (FXIII) and fibrinogen. However, the role of FXIII level in bleeding-related outcomes is unknown. ObjectivesTo evaluate the association between FXIII levels at hospital arrival and critical administration threshold (≥3 red blood cell units in 1 hour within the first 24 hours), bleeding-related outcomes, death, and baseline characteristics. MethodsA retrospective cohort study was conducted in severely injured adult patients (Injury Severity Score of ≥22 or ≥2 red blood cell units transfused in 24 hours) admitted to a level 1 trauma center. Clinical and laboratory data were collected. Baseline FXIII antigen levels were measured in banked patient plasma. Multivariable logistic and linear regression models were used to estimate the association between FXIII levels, outcomes, and baseline characteristics. ResultsThree hundred sixty-four of 1730 subjects admitted during a 2-year period were analyzed. Median age was 44 years (IQR, 27-62 years), and median Injury Severity Score was 29 (IQR, 22-34). FXIII levels were not associated with critical administration threshold (odds ratio [OR], 1.06; 95% CI, 0.97-1.17) or death (OR, 0.98; 95% CI, 0.90-1.07). FXIII was associated with major bleeding (OR, 1.10; 95% CI, 1.02-1.2) and massive transfusion (OR, 1.25; 95% CI, 1.08-1.44). Lower baseline FXIII levels were associated with arrival from a referring hospital (FXIII level, −0.07 U/mL; 95% CI, −0.11 to −0.03), hemoglobin (FXIII level, −0.05 U/mL; 95% CI, −0.07 to −0.03), fibrinogen level (FXIII level, −0.05 U/mL; 95% CI, −0.08 to −0.02), and platelet count (FXIII level, −0.02 U/mL; 95% CI, −0.04 to −0.008). ConclusionsBaseline FXIII levels in severely injured patients were inconsistently associated with bleeding-related outcomes and mortality. However, their association with major bleeding warrants further investigation of the role of FXIII in massively transfused patients with trauma.

Efficacy of new hemostatic techniques in nonvariceal gastrointestinal bleeding: A systematic review and network meta-analysis.

Nonvariceal gastrointestinal bleeding (NVGIB) is a common medical condition with significant mortality and morbidity. Several types of hemostatic modalities are currently available in clinical setting. This systematic review and network meta-analysis aimed to assess the efficacy of these modalities in treating NVGIB. PubMed, EMBASE, and the Cochrane Library databases were searched for studies that compared the efficacy of different hemostatic techniques (over-the-scope clip [OTSC], hemostatic powder [HP] and conventional endoscopic treatment [CET]) for NVGIB published up to June 2022. The 30-day rebleeding rate was regarded as the primary outcome. We performed pairwise and network meta-analyses for all treatments. The heterogeneity and transitivity were evaluated. Twenty-two studies were included. Regarding the 30-day rebleeding rate, OTSC and HP plus CET showed superior efficacy in treating NVGIB compared with CET (OTSC vs CET: relative risk [RR] 0.42, 95% confidence interval [CI] 0.28-0.60; HP plus CET vs CET: RR 0.40, 95% CI 0.17-0.87), while OTSC and HP plus CET had comparable efficacy (RR 0.95, 95% CI 0.38-2.31). HP plus CET ranked the highest in the network ranking estimate. The sensitivity analysis showed that it was not robust that OTSC was superior to CET regarding the short-term rebleeding rate and the initial hemostasis rate. While all-cause mortality, bleeding-related mortality and necessity of surgical or angiographic salvage therapy showed no statistically significant difference. OTSC and HP plus CET significantly reduced 30-day rebleeding rate compared to CET and had comparable efficacy in the treatment of NVGIB.

Bleeding related hospitalizations and mortality in England 2014-2019.

Acute bleeding is common and associated with increased morbidity and mortality. Epidemiological studies evaluating trends in bleeding-related hospitalisations and mortality are important as they have potential to guide resource allocation and service provision, however, despite this literature evaluating the national burden and annual trends are lacking. Our objective was to report the national burden and incidence of bleeding-related hospitalisation and mortality.This was a population-based review of all people in England between 2014 and 2019 either admitted to an acute care ward of a National Health Service (NHS) English hospital, or who died. Admissions and deaths were required to have a primary diagnosis of significant bleeding.There was a total of 3,238,427 hospitalisations with a mean of 539,738 ± 6033 per year and 81,264 deaths with a mean of 13,544 ± 331 per year attributable to bleeding. The mean annual incident rate for bleeding-related hospitalisations was 975 per 100,000 patient years and for mortality was 24.45. Over the study period there was a significant 8.2% reduction in bleeding related deaths (χ2 test for trend 91.4, p < 0.001). A direct relationship between increasing age and incidence of bleeding-related hospitalisation and mortality was seen.Bleeding remains a common cause of hospitalisation and death. The reduction in bleeding related mortality requires further investigation. This data may serve to guide future interventions designed to reduce bleeding-related morbidity and mortality.

AB089. SOH23ABS_147. A systematic review and meta-analysis of the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery

Background: Maternal mortality remains a major healthcare challenge worldwide with 27% of all maternal deaths attributed to haemorrhage. Tranexamic acid (TXA) is widely available and has been shown to reduce the need for transfusion in elective surgery and bleeding related mortality in women who suffer a postpartum haemorrhage (PPH).