Emergency surgery for acute rectal bleeding in a newly diagnosed case of fulminant ulcerative colitis.

INTRODUCTION: The incidence of ulcerative colitis is rising among Asian population. Massive bleeding per rectum is an uncommon, but serious, complication of UC accounting for 0.1-1.4 % of admissions. CASE PRESENTATION: A 22-year-old male, reported persistent abdominal pain, bloody diarrhea, and intermittent vomiting for one week. Physical examination revealed signs of dehydration and pallor. Laboratory tests showed elevated inflammatory markers. CT and colonoscopy confirmed ulcerative colitis, refractory to corticosteroids, leading to a subtotal colectomy followed by Ileal Pouch-Anal Anastomosis. The patient was symptom free at a 24-month follow-up. DISCUSSION: Bleeding that occurs during the initial stages of the disease or in cases where the diagnosis of ulcerative colitis hasn't been confirmed makes it challenging for patients to accept the need for extensive surgery and the creation of a stoma. Conservative procedures are advised in such settings. CONCLUSION: Acute severe bleeding in ulcerative colitis is rare but demands a multidisciplinary approach for timely diagnosis and treatment. In resource and expertise limited situation, where patients are noncompliant to regular follow-ups surgical treatment can still be intervention of choice for these cases.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Management of critical bleeding.

The management of major bleeding is a critical aspect of modern healthcare and it is imperative to emphasize the importance of applying Patient Blood Management (PBM) principles. Although transfusion support remains a vital component of bleeding control, treating severe bleeding goes beyond simply replacing lost blood. A more comprehensive, multidisciplinary approach is essential to optimize patient outcomes and minimize the risks associated with excessive transfusions.

Survey of policies at US hospitals on the selection of RhD type of low-titer O whole blood for use in trauma resuscitation.

BACKGROUND: Low-titer group O whole blood (LTOWB) use is increasing due to data suggesting improved outcomes and safety. One barrier to use is low availability of RhD-negative LTOWB. This survey examined US hospital policies regarding the selection of RhD type of blood products in bleeding emergencies. STUDY DESIGN AND METHODS: A web-based survey of blood bank directors was conducted to determine their hospital's RhD-type selection policies for blood issued for massive bleeding. RESULTS: There was a 61% response rate (101/157) and of those responses, 95 were complete. Respondents indicated that 40% (38/95) use only red blood cells (RBCs) and 60% (57/95) use LTOWB. For hospitals that issue LTOWB (N = 57), 67% are supplied only with RhD-positive, 2% only with RhD-negative, and 32% with both RhD-positive and RhD-negative LTOWB. At sites using LTOWB, RhD-negative LTOWB is used exclusively or preferentially more commonly in adult females of childbearing potential (FCP) (46%) and pediatric FCP (55%) than in men (4%) and boys (24%). RhD-positive LTOWB is used exclusively or preferentially more commonly in men (94%) and boys (54%) than in adult FCP (40%) or pediatric FCP (21%). At sites using LTOWB, it is not permitted for adult FCPs at 12%, pediatric FCP at 21.4%, and boys at 17.1%. CONCLUSION: Hospitals prefer issuing RhD-negative LTOWB for females although they are often ineligible to receive RhD-negative LTOWB due to supply constraints. The risk and benefits of LTOWB compared to the rare occurrence of hemolytic disease of the fetus/newborn (HDFN) need further examination in the context of withholding a therapy for females that has the potential for improved outcomes.

Plasma-derived human factor X concentrate for the treatment of patients with hereditary factor X deficiency.

INTRODUCTION: Hereditary factor X (FX) deficiency (HFXD) is an autosomal recessive rare bleeding disorder that leads to defects in the FX protein. Depending on the degree of deficiency, patients may be at risk of life-threatening bleeding episodes. Historical treatments for FX deficiency include prothrombin complex concentrates, which can increase the risk of thrombosis, and fresh frozen plasma, which can cause volume overload and transfusion reactions. Plasma-derived FX (pdFX), a single-factor, high-purity, high-potency human FX treatment, was approved in 2015 in the United States and in 2016 in Europe for on-demand treatment and prophylaxis of bleeding episodes and perioperative management of patients with HFXD. METHODS: Five studies that examined the use of pdFX in patients with mild (plasma FX activity [FX:C] ≥5 IU/dL), moderate (FX:C ≥1 and <5 IU/dL), or severe (FX:C < 1 IU/dL) HFXD were reviewed: TEN01, TEN02 and TEN03 were prospective, open-label, multicentre, nonrandomised studies, and TEN05 and TEN06 were multicentre retrospective studies. RESULTS: When used as an on-demand treatment, pdFX was judged by investigators to be successful in treating 41/42 (97.6%), 2/3 (66.6%) and 79/79 (100%) bleeds in TEN01, TEN02 and TEN05, respectively. When used prophylactically, pdFX was judged 'excellent' for the prevention of bleeds in nine (100%) and eight (100%) patients in TEN02 and TEN05, respectively. Perioperative treatment and pharmacokinetics were also assessed. pdFX was safe and well tolerated. CONCLUSIONS: Together, these studies support the use of pdFX for on-demand treatment of bleeding, routine prophylaxis, and perioperative management of bleeding in patients with HFXD.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Management of critical bleeding

Abstract The management of major bleeding is a critical aspect of modern healthcare and it is imperative to emphasize the importance of applying Patient Blood Management (PBM) principles. Although transfusion support remains a vital component of bleeding control, treating severe bleeding goes beyond simply replacing lost blood. A more comprehensive, multidisciplinary approach is essential to optimize patient outcomes and minimize the risks associated with excessive transfusions.

A life-threatening bleeding prediction model for immune thrombocytopenia based on personalized machine learning: a nationwide prospective cohort study.

Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.

Value of the FDP/FIB ratio in predicting early severe bleeding events in patients with newly diagnosed acute promyelocytic leukemia.

Severe bleeding is the leading cause of early death in patients with newly diagnosed acute promyelocytic leukemia (APL). However, there are no means for hemorrhagic risk stratification in APL. This study aimed to identify optimized predictors of severe bleeding events related to APL. A total of 109 consecutive patients with newly diagnosed APL from January 2015 to April 2022 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical date, including baseline characteristics, routine blood examination findings, coagulation and fibrinolysis indexes, and bleeding events. Among the 109 patients, 89 were classified into the no-severe bleeding group, while 20 had severe bleeding. Compared with the patients with no severe bleeding, the patients with severe bleeding had significantly higher circulating leukemic cell percentages, disseminated intravascular coagulation (DIC) scores, D-dimer (D-D) levels, and fibrin degradation product (FDP) levels. They also had lower fibrinogen (FIB) levels and a longer prothrombin time. Multivariate analysis revealed that the circulating leukemic cell percentage (OR = 1.040, CI = 1.008-1.072, P = 0.012), FIB level (OR = 0.101, CI = 0.011-0.896, P = 0.040), and FDP level (OR = 1.012, CI = 1.000-1.024, P = 0.047) were independent risk factors for severe bleeding. FDP/FIB, D-D/FIB, and seven meaningful indicators in the single-factor analysis were included in the receiver operating characteristic (ROC) curve analysis. The results showed that FDP/FIB was the best indicator for predicting severe bleeding related to newly diagnosed APL. The area under the ROC curve of FDP/FIB was 0.915, and the best cutoff value was 61.77, with 100% sensitivity and 74.2% specificity. Statistical analysis showed a higher incidence of severe bleeding and higher DIC scores when FDP/FIB was >61.77 in APL patients. FDP/FIB has obvious advantages in predicting the degree of bleeding associated with primary promyelocytic leukemia; the greater the FDP/FIB value, the more severe the bleeding. The risk of severe bleeding was the highest when FDP/FIB > 61.77.

Temporal trends in admissions for atrial fibrillation and severe bleeding in England: an 18-year longitudinal analysis.

Objective. Temporal trends in admissions for atrial fibrillation (AF) and severe bleeding associated with AF vary worldwide. We aimed to explore their temporal trends in England and their relation to the introduction of DOACs in 2014 in the UK. Design. This longitudinal ecological study utilised aggregated data that was extracted from the Hospital Episode Statistics database, which captured annual admissions for AF and severe bleeding associated with AF between 2001 and 2018. Trends in admissions over the study period and across age groups, gender and regions in England were assessed. Results. In total, there were 11,292,177 admissions for AF and 324,851 admissions for severe bleeding associated with AF. There was a steady rise in admissions for AF from 2001 to 2017 (204,808 to 1,109,295; p for trend<.001). A similar trend was observed for severe bleeding (4940 to 30,169; p for trend <.001), but the increase dropped slightly between 2013 and 2014 and continued thereafter. Conclusions. There was a rise in admissions for AF and severe bleeding in England between 2001 and 2018. There is little evidence that the slight drop in admissions for severe bleeding between 2013 and 2014 may have been caused by the introduction of DOACs in 2014. Contributors to these trends need urgent exploration.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Factor XIII Measurement and Substitution in Trauma Patients after Admission to an Intensive Care Unit.

Trauma patients admitted to an intensive care unit (ICU) may potentially experience a deficiency of coagulation factor thirteen (FXIII). In this retrospective cohort study conducted at a specialized trauma center, ICU patients were studied to determine the dependency of FXIII activity levels on clinical course and substitution with blood and coagulation products. A total of 189 patients with a median injury severity score (ISS) of 25 (16−36, IQR) were included. Abbreviated injury scores for extremities (r = −0.38, p < 0.0001) but not ISS (r = −0.03, p = 0.45) showed a negative correlation with initial FXIII levels. Patients receiving FXIII concentrate presented with a median initial FXIII level of 54 (48−59)% vs. 88 (74−108)%, p < 0.0001 versus controls; they had fewer ICU-free days: 17 (0−22) vs. 22 (16−24), p = 0.0001; and received higher amounts of red blood cell units: 5 (2−9) vs. 4 (1−7), p < 0.03 before, and 4 (2−7) vs. 1 (0−2), p < 0.0001 after FXIII substitution. Matched-pair analyses based on similar initial FXIII levels did not reveal better outcome endpoints in the FXIII-substituted group. The study showed that a low initial FXIII level correlated with the clinical course in this trauma cohort, but a substitution of FXIII did not improve endpoints within the range of the studied FXIII levels. Future prospective studies should investigate the utility of FXIII measurement and lower threshold values of FXIII, which trigger substitution in trauma patients.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Risk Factors for Severe Bleeding Complications in Glaucoma Surgery and the Role of Antiplatelet or Anticoagulant Agents.

Purpose: To evaluate the influences and risk factors for severe bleeding complications during glaucoma surgery, and to investigate the role of antiplatelet (AP) and anticoagulant (AC) agents. Methods: This prospective study enrolled patients undergoing trabeculectomy, trabeculotomy (with Trabectome® or Kahook Dual Blade®), viscocanaloplasty and Ahmed or Baerveldt implants. Bleeding severity was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and one day later, the incidence and severity of bleeding events was documented on a standardized form. A grade ≥3 was defined as severe bleeding. The influence of known systemic disorders, the type of anesthesia, surgical procedure, intraoperative blood pressure, and the use of or change in AP or AC agents on intraoperative bleeding were analyzed. Results: Data from 89 eyes undergoing glaucoma procedures were included (age 71.3y ± 10.5). We observed severe intraoperative bleeding in 8 eyes (9%) and found that concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease, and the type of surgical procedure (trabeculectomy and viscocanaloplasty) were significantly associated with severe bleeding events. By contrast, the use of AP/ AC agents had no significant influence on severe intraoperative bleeding events. Conclusion: According to the results of our study cohort, glaucoma procedures entailing scleral manipulations (trabeculectomy and viscocanaloplasty) and concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease influence the risk of severe intraoperative bleeding events, we detected no increased risk related to concomitant antiplatelet and/ or anticoagulant medication use.

Predictive factors for differentiating thrombohemorrhagic disorders in high-risk acute promyelocytic leukemia.

INTRODUCTION: Acute promyelocytic leukemia (APL) is often accompanied by potentially fatal coagulopathy, especially in high-risk APL. Bleeding, particularly severe bleeding is the leading cause of early death (ED). Meanwhile, thrombosis, the other major coagulopathic complication, is being increasingly recognized. However, predictors of thrombohemorrhagic disorders are still not well investigated. MATERIALS AND METHODS: In this study, we retrospectively studied 83 patients with high-risk APL and categorized them into severe bleeding, thrombosis and no evident events groups. RESULTS: Severe bleeding was observed in 15 patients, nearly half of whom died of hemorrhage, while thrombosis was observed in 12 patients. Risk factor analysis showed that high WBC (>58.76 × 109/L) (p = 0.001) and prolonged PT (>17.7 s) (p = 0.015) could be independent predictors for severe bleeding, while high WBC/D-dimer>5.12 (p = 0.002) and low D-dimer/FIB<5.14 (p = 0.03) could be independent predictors for thrombosis in high-risk APL patients. Moreover, there are significant differences in WBC/D-dimer and D-dimer/FIB between DIC and Non-DIC groups (p < 0.001). Notably, we found that the WBC/D-dimer was dramatically higher in the thrombotic group than in the other two groups at the time of admission or during the first week of induction therapy. CONCLUSIONS: High WBC and prolonged PT could predict severe bleeding in high-risk APL patients, while high WBC/D-dimer and low D-dimer/FIB could be independent predictors for thrombosis. For high-risk APL, WBC/D-dimer and D-dimer/FIB are also beneficial in the diagnosis of DIC. WBC/D-dimer might help early identification of thrombosis at the time of admission or during the first week of induction therapy.

Editor's Choice - Severe Bleeding Risks of Direct Oral Anticoagulants in the Prevention and Treatment of Venous Thromboembolism: A Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6). CONCLUSIONS: For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

Excess weight gain in the paediatric bleeding disorders population: Impact of the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has resulted in lifestyle changes for children. The aim of this study was to evaluate the impact of the pandemic on weight/BMI in children with severe bleeding disorders. METHODS: We conducted a retrospective review of patients age 3-18 years with severe bleeding disorders on prophylactic therapy treated at SickKids Hospital (Toronto, Canada) between February 01, 2018 and March 31, 2021. We evaluated the following pre- and post-COVID variables: weight (kg), weight percentile, BMI (kg/m2 ), BMI percentile, HJHS score, and prophylactic dosing (units/kg). RESULTS: One hundred and four patients were included in the final analysis. Diagnoses were as follows:  haemophilia A (n = 92; 70.8%), haemophilia B (n = 17; 13.1%), type 3 von Willebrand disease (n = 11; 8.5%), the remainder were diagnosed with rare factor deficiencies.  Median interval time from pre-COVID measurements to latest follow-up was 12.4 months (IQR 10.32-14.52 months) during which there was a statistically significant increase in median weight percentile +5.75 centiles (from 63rd centile to 68.75th centile). There was a statistically significant increase in mean BMI of +1.03 kg/m2 (P = < .001) while median BMI percentile increased +8.82 centiles (from 53.9th centile to 62.72nd centile) and mean BMI percentile increased 3.42 centiles (from 57.5 centile to 60.9 centile). The group that gained the most weight centiles, BMI and BMI centiles were 5-14 years old. CONCLUSION: There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Background: Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis. In a post hoc analysis, we evaluated the incidence and severity of pulmonary bleeding in patients with bronchiectasis who were hospitalized for an acute medical illness. This analysis included MAGELLAN patients diagnosed with bronchiectasis at baseline. Patients were evaluated by treatment group for International Society on Thrombosis and Haemostasis major bleeding, non-major clinically relevant (NMCR) bleeding, and the composite of the 2 (ie, clinically relevant bleeding). Results: Medically ill patients with bronchiectasis were randomized to rivaroxaban (n = 60) or enoxaparin/placebo (n = 61). There were 2 fatal pulmonary bleeds and 1 fatal gastrointestinal bleed in the rivaroxaban arm and no fatal or major bleeding in the enoxaparin/placebo arm. The incidence of major bleeding was 5% in the rivaroxaban arm. One NMCR bleed occurred in the rivaroxaban arm and 2 NMCR bleeds occurred in the enoxaparin/placebo arm. The incidence of clinically relevant bleeding was 6.7% versus 3.3% in the rivaroxaban and enoxaparin/placebo groups, respectively (relative risk = 2.06 [95% confidence interval: 0.351-12.046]). Conclusion: In-patients hospitalized with bronchiectasis and an acute medical illness, clinically relevant bleeding, including fatal pulmonary hemorrhage, occurs more frequently with extended rivaroxaban thromboprophylaxis than with enoxaparin followed by placebo.

Occurrence and management of severe bleeding episodes in patients with hereditary factor X deficiency.

Vitamin K-dependent factor X (FX) plays an important role in thrombin formation, and a deficiency in FX can cause impaired coagulation, the severity of which is usually correlated with the degree of deficiency. Due to the critical role that FX plays in the coagulation cascade, FX deficiency is associated with a higher risk of bleeding than deficiencies in other coagulation factors. Patients with the hereditary autosomal-recessive homozygous form of FX deficiency, which occurs in approximately 1:1,000,000 individuals worldwide, are often diagnosed when they present with spontaneous life-threatening haemorrhage (most often intracranial haemorrhage) during the first month of life. In addition to central nervous system bleeds, other severe bleeding types experienced by such patients may include umbilical cord bleeding, gastrointestinal or pulmonary haemorrhage, intramuscular haematomas and/or haemarthrosis. Delayed treatment or inadequate replacement of FX may result in developmental delays, musculoskeletal disabilities or death. The high risk of recurrent severe bleeding necessitates prophylactic replacement therapy for many individuals with severe FX deficiency. Available products for replacement therapy include plasma-derived FX concentrate and prothrombin complex concentrates. Fresh-frozen plasma may be used when concentrates are not available but is a less efficient means of FX replacement. This article reviews the literature on severe bleeding in individuals with hereditary FX deficiency and discusses current treatment options.

HLA-DQB1 mismatch increase risk of severe bleeding independently in recipients of allogeneic stem cell transplant.

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31-3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54-48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients.

Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents.

PURPOSE: To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. DESIGN: Prospective trial. PARTICIPANTS: Patients undergoing vitreoretinal surgery. METHODS: The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. MAIN OUTCOME MEASURES: Incidence and risk factors for severe intraoperative bleeding events. RESULTS: Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6 ± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. CONCLUSIONS: Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.

Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. METHODS: In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. RESULTS: FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2 = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. CONCLUSION: The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.